Weight regain following weight loss

Biological mechanisms that promote weight regain following weight loss in obese humans.

Great paper here, summarizing the research on why maintaining weight loss is so difficult AND also the foolishness of calorie restriction.

This article discusses research on several factors that may contribute to weight regain following weight loss achieved through behavioural interventions, including adipose cellularity, endocrine function, energy metabolism, neural responsivity, and addiction-like neural mechanisms. All of these mechanisms are engaged prior to weight loss, suggesting that these so called "anti-starvation" mechanisms are activated via reductions in energy intake, rather than depletion of energy stores.

The bolded part is the key part of this paper. The author's are arguing that it is not weight loss per se that sets us up for weight regain, but rather it is the calorie restriction. I posted on another study earlier this year which also seemed to support this idea, here, in that post, we found that mice who lost weight by 40% calorie restriction had a dramatic increase in AgRP, while mice that were allowed to eat ad-lib on a new diet did not increase AgRP but still lost considerable weight. Whats funny is that the author of the above study makes no mention of the AgRP study I blogged about, so unwittingly he is on the right tracks. imo.

 The whole paper is golden so if you can get the full text its well worth a complete read. I tried and failed to paraphrase it, every sentence has useful information. So I just copy paste the beginning of the discussion and the conclusion...

Changes in adipose cellularity and addiction-like neural habituation result from chronic overconsumption and appear irreversible via behavioral weight loss [24,34,122,129]. Thus, these factors are not activated to prevent weight loss but serve to encourage preservation of highest sustained body weight, and may actually promote indefinite increases in energy storage. Alterations in endocrine function (e.g., decreases in leptin and increases in ghrelin), decreases in energy expenditure, and increases in neural responsivity to high-calorie food cues all occur within 24 h of caloric restriction (Table 1) [57,84,132]. 

Regardless of when these mechanisms are activated, each has the potential to exert a [neuro]biological influence that may reduce an obese or formerly obese individual's ability to maintain behavioral weight losses and promote weight regain at least to the individual's highest sustained lifetime weight. These influences also carry the expected weight regain promoting behavioral correlates. 

Weight-reduced vs. never-obese subjects report increased food craving [133], a decreased perception of amount eaten [134], decreased postprandial satiety [135] and an increased preference for calorically dense foods [136].With these additional biological influences encouraging the consumption and storage of energy, it is not surprising that weight regain following behavioral weight loss occurs at a faster rate than initial weight gain [135,137].

These mechanisms appear not to be part of a highly sensitive homeostatic feedback system designed to regulate body weight at any particular “set point,” but mechanisms either acquired via excess weight gain or enacted almost immediately via reduced caloric intake. Importantly, these mechanisms operate irrespective of the adequacy of energy stores. Thus, these mechanisms may be more accurately described as anti-weight loss mechanisms, rather than anti-starvation mechanisms per se.

CONCLUSION

We have presented evidence that the likelihood of weight regain in weight-suppressed obese and formerly obese individuals may be increased by a confluence of biological mechanisms, including adipose hyperplasia, increased metabolic efficiency, changes in neuroendocrine signaling (e.g., decreased satiety signaling), and changes in neural responsivity to both food cues (e.g., increased reward-related or decreased inhibitory anticipatory responsivity) and food intake (e.g., decreased consummatory reward through habituation to the rewarding aspects of palatable food). 

These biological pressures that may undermine weight loss efforts and promote weight regain are almost immediately enacted in obese individuals attempting even modest and healthy weight reduction. Further, these mechanisms operate invariably and appear to defend an individual's highest sustained body weight. Thus, it is the opinion of these authors that these mechanisms would be more accurately described as anti-weight loss mechanisms rather than anti-starvation mechanisms. Regardless, obese individuals face an extreme uphill battle in having to overcome powerful biological drives that appear insurmountable via behavioral interventions, illustrating the critical importance of obesity prevention efforts for normal and overweight individuals. This may be particularly pertinent to parents of overweight children, who are significantly more likely to become obese adults.

p.s. thanks to bill/caloriesproper for the full text.

EDIT -- Added the parts on adipose morphology and leptin

Excess weight gain typically leads to changes in body composition, including significant alterations in adipose cellularity. Although increases in body mass index (BMI) do not directly predict an absolute increase in body fat content [19], elevated body weight is generally associated with an increase in the diameter of fat cells (adipocyte hypertrophy), as well as greater amounts of fat stored within adipocytes [20,21]. Most literature points to adipocyte hypertrophy as the main feature of obesity; however, alterations in adipocyte number may also be important [22,23]. Upon reaching an upward critical limit in fat cell volume, enlarged adipocytes secrete paracrine factors that induce preadipocyte proliferation (hyperplasia) [24–26]. Thus, excess caloric intake* may lead to increases in fat cell size and subsequent increases in fat cell number [20,26,27].

Recent evidence suggests that this increase in fat cell number may occur in overweight individuals [28]. However, the preponderance of evidence suggests that hyperplasia occurs primarily in clinically severely obese individuals [27,29,30]. Thus, if hyperplasia is associated with weight regain, this effect may be relegated to weight regain following weight loss in [formerly] clinically severely obese individuals, for whom returning to a lean bodyweight through behavioral weight loss is exceedingly difficult [31].

With behavioral weight loss, adipocyte hypertrophy decreases; however, the hyperplasia remains [20,29,32–35]. Thus, weight loss dieting may reduce the size but not the number of fat cells. A lack of programmed cell death may be responsible for the failure of reductions in fat mass via nonsurgical means to reduce adipocyte number [20,33]. Therefore, relative to never-obese individuals, weight-suppressed [formerly] obese individuals (particularly clinically severely obese individuals) may be left with a significantly greater number of adipocytes, which cannot be reduced via behavioral weight loss [34]. See Table 1.

Liposuction is the only known treatment able to reduce adipocyte number, but carries high complication rates [36]. It is not yet definitively known whether hyperplasia encourages weight regain in weight-suppressed individuals. There is some evidence to suggest that the presence of smaller adipocytes may encourage weight regain by decreasing the overall rate of fat oxidation and increasing the retention of ingested fuel [37–41]. Normally, during times of energy deprivation, fat stores break down triglycerides into their individuals components, glycerol and free fatty acids [42], which generate energy for the cell. However, the rate of fat breakdown (lipolysis) appears to be related to adipocyte size and cellular surface area [43]; smaller cells exhibit lower rates of basal lipolysis [44]. Therefore, if size-reduced adipocytes are modified to break down less and store more fat, these cells may expand and promote further proliferation. Although still speculative, there is some evidence to suggest that these cells may be predisposed to reach a particular mean size, allowing them to store similar amounts of fat as previously formed adipocytes [25,34].

However, small adipocyte number may be sufficient to observe a clinically significant effect in only a percentage of obese (i.e., clinically severely obese) individuals.An additional line of evidence reports higher levels of insulin in newly size-reduced adipocytes [44,45]. Insulin, which is excreted from pancreatic beta cells in response to rising levels of glucose in the bloodstream, facilitates a preferential utilization of carbohydrates to meet the cell's energy requirements [40,46–48]. Further, insulin inhibits lipolysis [49] and stores triglycerides in adipocytes (lipogenesis) [50].

Interestingly, although insulin sensitivity seems to improve in weight reduced individuals, fat metabolism slows, potentially in an attempt to preserve energy stores [37,38,49,50]. As a result of these changes in carbohydrate and fat utilization, an abnormal accumulation of triglycerides may give rise to a higher net fat cell content and elevations in body weight [37,38,51–53]. Adipocyte size is also correlated with plasma leptin concentrations, which have been shown to affect weight loss maintenance [54]. Relative to control, formerly obese weight-suppressed participants were found to have reduced fat cell volume and serum leptin levels, despite almost identical body fat percentages [35].

Because smaller adipocytes in formerly obese individual smay be secreting less leptin following behavioral weight loss [28,35,37,55], an association between increased number of smaller adipocytes and leptin insufficiency has been proposed
[28,35,37,55,56].

Although leptin levels are not entirely depleted in weight-suppressed formerly obese individuals, their secretions are much more attenuated relative to lean subjects who undergo caloric restriction [35,55]. Thus, with reductions in leptin secretion, heightened appetite and excess food intake may lead to weight regain [28,54]. The potential role of leptin in weight regain is further discussed below.


LEPTIN



Leptin levels are reduced within 24 h of energy restriction [57] and a number of studies report greater reductions of leptin than would be expected for given losses of adipose tissue [34,35,58]. It has been suggested that leptin's primary role is the prevention of starvation, rather than weight regulation per se, questioning the notion of “leptin resistance” [18]. Reductions in leptin levels appear to trigger a starvation defense response, despite the persistence of abundant fat stores [57]. Evidence suggests that there may be a threshold below which the “anti-starvation” action of leptin is enacted, and this threshold is proposed to increase concurrently with increases in adipose tissue [57].

Thus, weight loss dieting in obese individuals may lead to leptin depletion to sub-threshold levels, despite the persistence of relatively high levels of leptin. Sub-threshold leptin levels result in reductions in metabolic rate and physical activity [14], as well as increases in hunger and food intake [59]. Thus, behavioral weight loss and weight loss maintenance are accompanied by physiological attributes that resemble those of a leptin-deficient animal: lower energy expenditure, increased hunger, reduced thyroid metabolism, and diminished sympathetic nervous activity [60,61].

*I think that excess caloric intake quote is very ignorant of the author's. It is much more appropriately stated as excess storage of fat and/or insufficient mobilization of fat.

An easy way to increase testosterone......

During my research into steroids one of the more interesting studies that cropped up was this.....

Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin (exemestane), in young males.

Aromasin is an aromatase inhibitor, it works by binding irreversibly to the aromatase enzyme, so that other steroids like testosterone cant bind to it. In this study young males were given 25mg per day ( which is the standard tablet size ) for 10 days.

At the end of the 10 days, total testosterone had increased ~60% but free testosterone ( that is, the testosterone that is actually free to bind the androgen receptor ) increased by 117%. The reason this works is because estrogen is reduced as a result of the aromatase blockage, and estrogen is the main negative feedback signal to the hypothalamus to decrease LH secretion. So with lower estrogen in the system, more LH is secreted and more testosterone is made. Its a double whammy aswell, because with aromatase blockage, less testosterone is lost in the conversion to estrogen.

Infact another recent report even suggested aromatase inhibitors may be of benefit to obese men who suffer from hypogonadism due to the excess estrogen that usually accompanies obesity.

Whether or not this increased testosterone will result in anabolic affects however is up for debate. However if you think your suffering from low testosterone, aromasin could be of some help. Aromasin is actually quite a safe drug, with minimal side affects, but it is slightly pricey.

Note in the first study, estrogen levels returned to normal 3-6 days after aromasin withdrawal, so the drug must be continuously taken to keep the increased levels of testosterone. Bear in mind also, estrogen is actually a very important hormone in men, lower is not necessarily better. Low estrogen will absolutely murder your sex drive and ability to get an erection, in a similar way low testosterone will.

Insulin "turbocharges" conversion of testosterone to estrogen

This may be old news to many.....

So aromatase converts testosterone to estrogen, and aromatase activity is greatly increased by insulin, something of which we all seem to have too much of in our modern society. ( insulin that is )

Here is an interesting passage from this paper.....

The physical effects of illness and inflammation, and the psychological stress associated with concern about being loved and accepted by family and peers, compounded by work pressure, financial stress and the perceived urgency of daily living, all contribute to effectively increase corticotropin releasing hormone (CRH) Foster et al., 2009. The resultant pituitary adrenocorticotrophic hormone (ACTH) and corticosterone output stimulate the increased consumption of sweet and palatable carbohydrates (Dallman et al., 2007), including foods that contain 30% sucrose (like many breakfast cereals, cakes, biscuits, and confectionary), that stimulate a normal reactive insulin response.

Unfortunately, the increased insulin output,

• upregulates P450 aromatase 6-fold (Samad, 2007),
•  increases leptin output (Thomas et al., 2000; Falconnier et al.,
• 2003; Manderson et al., 2003; Lindsay et al., 2004),
•  increases estrogen-receptor-alpha number and activity (Kaaks, 2008),  
• induces hypertriglyceridemia, sodium retention and hypertension (Biddinger and Kahn, 2006),
•  increases subcutaneous fat deposition (Shin et al., 2007),

Further from the author.....

In summary, continuing exposure to stress, compensatory eating, xeno-oestrogens, the pill, pesticides, oestrogenic chemicals, fast foods, soft drinks and poor quality carbohydrate diets, cyclically amplify aromatase to TURBOCHARGE the production of even more oestradiol. . .until overweight becomes obesity, stress becomes depression, glucose intolerance becomes type two diabetes, benign prostate and breast changes turn into prostate cancer and breast cancer, and acceptable forgetfulness progresses toward Alzheimer’s disease.

In reference to the bolded part, the author recognizes that it is the carbohydrates in the diet that need to be scrutinized, not the dietary fats. Personally I think the cause of gyno in people taking high doses of steroids/androgens actually comes from the "bulking" aspect of their diet that generally involves extremely high amounts of calories/carbohydrates/refined carbohydrates. All the insulin that follows such a diet no doubt "turbochargers" aromastase to convert all that testosterone your injecting into estrogen.

There is also the link between increased levels of stress and increased carbohydrate consumption that has been reported many times before. To be honest, unless you are financially well off, modern life is almost 24/7 stress.

IF your still on the fence to the eternal chicken and egg question of what comes first, insulin hyper-secretion or insulin resistance, but still want to reduce your aromatase activity. You can do either one of two things, reduce your insulin resistance, or reduce your insulin secretion. ( or both obviously ). Reducing insulin resistance is not something that can be done in an obvious way, otherwise we'd have a cure for type 2 diabetes. HOWEVER, reducing your insulin secretion is easily done by reducing carbohydrates in your diet.

My experience with steroids

As mentioned previously, I finished a steroid cycle some weeks ago and I just want to make a small blog post on my experiences.

Originally I started taking testosterone ( 500mg 1x injection per week, rotating quads and glutes ) to help with my depression. Another reason I started testosterone is also because I badly wanted to try  Anavar which was reported to be especially good at reducing subcutaneous belly fat. I couldnt run the Anavar alone you see, because it would result in shutdown of testicular production of testosterone.

Anyway, after spending sometime researching the whole subject ( which was really fascinating ) I decided to get over my needle anxiety and start a cycle. Im no bodybuilder, I wasnt looking to gain huge amounts of muscle, just to deal with my depression and re-composition my body a bit. The first thing I would say is that the injections themselves are relatively painless. I used a 25gauge needle, and apart from the awkwardness of injecting into your own bum it was much easier than I thought. There can be some after pain, referred to as *pip* ( post injection pain ). I did get this on my first few shots, but as my skill injecting improved so did the pip. One tip is not to let the needle wiggle around when its in the muscle.

It took about 2 weeks before I started to notice changes in musculature and strength, however I noticed psychological changes within 48 hours. Suddenly I was EXTREMELY confident, much more assertive than I normally am, and would hold eye contact much more during conversations. Contrary to poplar belief, I did not experience any change in aggressiveness. One thing that testosterone clearly does is greatly increase your belief in yourself. Libido also increased. and my forehead and chest got extremely greasy.

Luckily I experienced only a very mild increase in acne, some people apparently really breakout badly with acne with high androgens. 6 weeks into the cycle I had gained only small amounts of muscle, my belly fat had gone down quite a bit which I was happy with ( thanks Anavar ), and my strength was up ALOT. But by far the best improvements were the psychological ones, the feeling of well-being was euphoric. Steroids make you feel like you can do *anything*.

At this point I made a big mistake and added Trenbolone. I dont know why, probably because I was still desperate to drop bodyfat plus so far I had experienced almost no negative side-effects from the testosterone and anavar. Trenbolone is notorious for its side-effects and I can say that is very true. I noticed immediately upon adding the Tren that I become short-tempered ( very unlike me ), but by far the worst thing was the insomnia, I was sleeping 3 hours per night and it was completely ruining me. One thing I noticed, which might be placebo, was that people seemed to be acting in a naturally more supplicating/timid way towards me while I was on the tren. I stopped going to the gym due to being completely fatigued all the time. And I was sweating badly constantly. I had to wait several weeks for it to clear form my system due to the long ester version.

After that, I increased the testosterone dosage to 750mg per week, then a few weeks later ended the cycle. I used HCG throughout cycle to avoid testicular atrophy. It is commonly advised to use an aromatase inhibitor during cycle to combat estrogen and gyno, HOWEVER I believe this is because most people running steroids are also running highly insulinogenic diets that promote hyperinsulinemia, and insulin is a strong activator of the aromatase enzyme. I spent alot of money on aromasin and found it to be a COMPLETE waste, because not once did I ever experience signs of high estrogen. ( I was still lowcarb during the cycle ). Infact the few times I did try taking the aromasin I immediately experienced signs of LOW estrogen, such as achy joints/spine and complete loss of libido.

Well, I am now 2 months since the end of my cycle, Ive lost pretty much all the muscle I had gained ( mostly because I stopped going to the gym ). however I do seem to have retained some of the strength gains. Yes, im going to run steroids again in the future, However I will stick to just testosterone, anavar, and dianabol. IF theres one thing I learnt its to keep side-effects to an absolute minimum.

I think the stigmatization surrounding steroids is completely overblown, sure they are open to abuse just like any drug. I find this especially amusing since just about EVERYONE in the sports and fitness industry is on steroids. ALL Olympic athletes are on these compounds, as most probably 99% of sports stars are. Even movie actors are taking these things in high doses just to look good for movies.  ( Thor, Bane, etc ).

Personally I predict a massive explosion of steroid use in the future, especially as we learn to control the negative side effects of them. People dont want to be just average, they want to be GREAT.



P.S. sorry for the dark tone this blog is taking, but I have warned people previously that this is my personal space.

Fats reduce protein catabolism?

Just a quick update, I dont really have time to blog at the moment since I have alot going on in my real life. My father died in June and I have been suffering with pretty severe depression since then. It caused me to start steroids, mainly because testosterone is the best anti-depressant available to men. Anyway, ive come off them now, it was interesting and certainly helped me cope with the depression. I also managed to fall for a girl I apparently have no chance with, which has been a MAJOR headache. So yeh, my life is pretty fucked up at the moment.

Well, I dont want to discuss too much of my personal goings on here, I found this study today which seems to provide some answer to the strange paradoxical question, why would you lose muscle mass on a hypo-caloric diet despite consuming surplus protein? ( say 800 calories per day 150g protein ).

Hepatic amino acid-degrading enzyme expression is downregulated by natural and synthetic ligands of PPARα in rats.

PPARalpha is activated by fats, including dietary fats, and according to this study PPARalpha down-regulates protein degradation. So in a strange way, eating fat may help with increasing or preserving muscle mass. I think this is a good explanation for as to why 2000 calories 150g protein 150g fat would be better for muscle mass than simply a 800 calorie diet with 150g protein.

I don't like lowcarb - to be honest

Just because I follow/advocate lowcarb, doesnt mean I like it. Infact, I think I almost hate it.

Dont get me wrong, I enjoy the lowcarb foods, ill eat fatty meat everyday, no complaints. BUT, I want potatoes with my steak, I want rice with my fish, I want baked beans with my bacon and eggs for breakfast. Yes, I love my carbohydrates, especially milk, it horrifies me to no end that I need to give up milk to get weight loss. ( I can be weight stable on milk but never weight loss ).

All last week I drank an additional 300ml  ( 1500 calories roughly ) of double cream on top of my normal zero carb intake, and well, my weight hasn't budged. To add insult to injury, my waist circumference has gone down *slightly*. What would of happened if I had added 1500 calories of potatoes/rice instead of the cream. FAT EXPLOSION. my trousers would be tight and my belly bloated.

Despite all the research ive done on this blog, I still dont have the answer. All I know is that keeping my carbs near zero gets and keeps my weight down.........effortlessly. I can eat plenty of cheese and get weight loss, but adding equivalent amounts of calories in milk stops weight loss. That REALLY bugs me. Especially since milk is quite gentle on blood sugar spikes.

With the amout of time ive spent trying to point out the fallacy of the CICO logic, the irony is id be much happier if CICO was infact true and all I had to do was watch my calories to control my weight because then I could enjoy my carbohydrates. BUT IT AINT FUCKING TRUE MAN. Its the bloody carbs controlling my fat mass. Im sick of telling myself everyday *CANT HAVE THAT,  its got some glucose molecules in it!*

I suppose id be happier if I wasnt actively trying to lose fat, I can maintain weight eating some carbs, but to lose I gotta go almost zero carb. Ive learnt im prone to hypoglycemia from exercise while zero-carbing. At the gym few days ago I almost passed out from light-headedness after a few mins on the step machine ( granted I was doing near max intensity ). I also feel a bit light headed after running up alot of stairs quickly. As far as my body is concerned, anaerobic exercise and zero carb dont mix.

Well, I dont know what the problem with carbs and my body is. It sucks other people can eat what they want and stay slim. I , meanwhile, have to cut out entire food groups. Damn, I want some marmite on toast, but jeez, if I touch toast ill wake up tomorrow +10lbs.

Growth hormone dosing + fat loss stacked with zero carb

I think I have found the sweet-spot for growth hormone dosing, 2ui ( of high quality version ) taken in the morning before any food seems to yield very good body re-composition results but at the same time doesnt result in it being overly expensive. Basically its a good balance between cost and results.

There are other options for increased GH, like GHRP2 + mod grf 1-29, this causes a spike in natural growth hormone produced by the body which has more isoforms than exogenous GH, this option is also much much cheaper but has a few side effects, GHRP2 can cause increased hunger and increased cortisol.

Anyway , GH combined with zero carb produces amazing fat loss. In the last 3 weeks I dropped 5cm on my waist and I can feel how much lighter I am walking around.  Ive had a few cheat days in those 3 weeks but on the whole ive been 75% zero carb for that duration. GH is associated with insulin resistance and in particular probably induces insulin resistance in adipocytes ( link ), no doubt this is how it helps you lose body fat.

Ive had to stop the melanotan II, a few people have made comments on how dark my face has gotten compared to the rest of my body. Basically because I spent all summer only exposing my face and neck to the sun, these body parts have become exceptionally dark tanned, while the rest of my body has only darkened a little. oh well, now I have wait a few months for the colors on my face/body to equalize before I can consider doing this again. Make a note, Melanotan II doesnt work so well without atleast *some* kind of UV exposure.

I also tried Ipamorelin which was quite interesting. Its another growth hormone secretagogue although its not as potent as GHRP2, it has way less side affects. However the reason I tried this peptide was because of various anecdotal reports on bodybuilding forums of it improving sleep. I took 100mcg 1 hour or so before bed and I can confirm that sleep is improved, the sleep is deeper and you feel more refreshed in the morning.

I have a sketchy theory as to how or why this might help sleep.

Ipam is a ghrelin mimetic, and ghrelin is a slow-wave sleep promotor. In particular, I can remember something quite odd back from this study which looked at 24hr ghrelin levels in obese vs lean subjects. As we all know, obesity is associated with poor sleep. Although the arrow of causation is still tricky. Which causes which? Anyway the most peculiar thing about this study was that at night during sleep, the lean subjects exhibited a large increase in ghrelin, while the obese subjects did not.

See here.......

The bolded black part on the bottom x-axis is the period where the subjects are sleeping and as you can see, the difference between lean and obese is quite startling. *Could* this be why obesity is associated with poor sleep? Either way, I can confirm that Ipam does help with sleep. Im not saying its a cure of insomnia, It doesnt even make you drowsy, but it does seem to help with deeper sleep once sleep comes on.

I think that, if your a bad sleeper, then you really need to try EVERYTHING to resolve this, sleep is probably THE most important thing when it comes to being in good health, It doesnt matter how perfect your lifestyle, diet, or anything else is, a bad nights sleep will trump ALL OF THAT and make you feel like shit.

Ketones inhibit fat synthesis

Metabolite regulation of nucleo-cytosolic trafficking of carbohydrate response element binding protein (ChREBP): role of ketone bodies.

Without going into all the technical details, here's the punchline....

 These observations show that ketone bodies play an important role in regulation of ChREBP activity by restricting ChREBP localization to the cytoplasm, thus inhibiting fat synthesis during periods of ketosis.

ChREBP is a transcription factor that is activated by increased glucose levels, and ChREBP increases synthesis of enzymes like fatty acid synthase that are responsible for lipogenesis.

Anyway what this paper implies is that high ketone levels will inhibit glucose induced lipogenesis.  I think potentially if your in ketosis this could probably mean that you can eat carbs for 1-2 days while stimulating only very limited lipogenesis. Basically the ability of carbs to cause fat gain should be curbed by high ketone levels. ( in theory ). However ofcourse repeated carb feeding will eventually kill your ketone levels and this will allow ChREBP to frontload its lipogenic power.

Now, who knows the answer to this question....... lets say you eat some carbohydrate, you activate ChREBP and it subsequently causes your cells to manufacture some fatty acid synthase enzymes. Now, how long do these enzymes sit around for? Whats their half life?



EDIT*

From the paper it seems oleate and linoleate also appear to be quite good at inhibiting ChREBP.

Hyperinsulinemia increases GLUT4 in white adipose tissue

Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance.

To mimick a state of hyperinsulinemia, normal rats were infused with insulin for 4 days via minipumps, and compared to saline infused rats. At the end of the experimental period, the abundance of mRNA was increased in white adipose tissue (WAT) and decreased in muscles of "insulinized" rats compared to controls. These findings were accompanied, in all tissues considered, except the diaphragm, by parallel changes in the amount of the glucose transporter protein and by parallel changes in the in vivo glucose utilization index. Hyperinsulinemia is thus a driving force in stimulating adipose tissue metabolic activity, while bringing about incipient muscle insulin resistance.

 Anyone got full text of this? I havent seen this study on the likes of carbsanity. But anyway its quite clear as I have said before, high fasting insulin is a nasty problem and it contributes to making you fat. The calories go where the GLUT4's are. Calories into muscle = lean and strong, calories into fat = obese and lazy.

Hyperinsulinaemia increases insulin action in vivo in white adipose tissue but not in muscles.

The effect of 4 days of stable hyperglycaemia and resulting hyperinsulinaemia on insulin-induced glucose utilization by individual rat tissues was studied in vivo. The treatment produced a net increase in the glucose utilization index under both basal and insulin-stimulated (euglycaemic/hyperinsulinaemic clamp) conditions in white adipose tissue. On the contrary, glucose utilization was unchanged in aerobic muscles but was decreased in glycolytic skeletal muscles during the clamp.

Old news but still noteworthy.

Melanotan II crushed my appetite.

So I been running this at 1mg per day for several weeks now, and im still nowhere near the tanning level I would like to be. As noted previously, theres been some developments however, my skin has undergone much higher pigmentation, lots of new freckles have shown up and some older freckles went REALLY dark. The strangest thing is , without sounding too crude, my penis has an amazing tan despite not seeing even a single photon of UV light.

I dont know what it is but my body is just severely resistant to tanning it seems. But the thing that has struck me the most is the reduction in appetite. Its been phenomenal. In the last week I have been literally having to force myself to eat, im currently running at around 1200 calories per day. Nothing in the fridge looks tasty. Most of my calories have been coming from milk. Even when I ordered a 15inch meat feast pizza I could only eat 2 slices before feeling COMPLETELY full, normally I could eat the whole thing no prob.

Today I even puked up half a tin of salmon I ate for dinner because it felt like "too many calories".

So have I lost any weight? Well yes, but I dont think its as much as it should of been given how little im eating.  Melanotan II has taught me that without a shadow of a doubt hormones control feeding. If your hungry and eating alot, its purely because your hormones are communicating this message to you, and has nothing to do with the reward value of the food or gluttony.

Human body is fucking shit trash

im so frustrated.

I sprained my ankle last Tuesday and its been the worst experience ever. Not only does it fucking hurt like hell, it takes AGES to fucking heal and I cant do shit at moment except ly in bed all day.

Seriously how the fuck did human evolution allow this type of injury to not be weeded out. It can happen SOOO easily and it just completely incapacitates you. In the wild youd be dead for certain with such a simple injury unless you had your family do EVERYTHING for you.

The more I learn about physiology the more I become convinced the human body is just a pathetic frail piece of trash.

Fucking amen for pharmaceuticals and drugs.

Chinese Growth Hormone + Melanotan II update

Ive been running some chinese growth hormone ( as opposed to pharma grade GH ) for the last 3 weeks. Chinese GH is suppose to be of dubious quality and/or under-dosed but I have to say, ive been VERY impressed with what I have been running. This shit is expensive as hell, each injection costs me £5, ( doing 3iu per day ). At 1 injection per day thats £150 per month.

Initially I became interested in GH because of the various reports that it can improve sleep, but there is way more to it than that it seems. The first thing I noticed is it seems to leave you with an amazing feeling of rejuvenation, like youve had a good restful nights sleep. If I take a shot in the morning when I get home from the nightshift I notice I feel much more refreshed when I wake up in the afternoon even after sleeping only 4 hours. Obviously my cognition is feeling shitty from the lack of sleep, but the rest of my feels pretty damn good to go.

This has lead me wonder if the major link between lack/loss of sleep and poor health is mostly attributable to low GH.

Also GH quite clearly made me drop some fat, without any change in my diet. Infact, I noticed I could eat quite a bit more junk and still stay not gain an inch around my waist, which for me is amazing since my waist is the first thing to expand when I gain fat. ( Gerry mentions the fat loss properties also here ). I dont care what people say, GH definitely pushes you towards leanness, and youll notice this affect literally within the first few shots.

Curious I ran a search on pubmed for growth hormone adipocyte and this study came up. CIDEA is the protein I briefly mentioned in a old post when I was looking at if maybe fasting could kill adipocytes. As spoke of previously, the bottom line is low CIDEA = you get fat

CIDE-A expression is significantly reduced in GHR -/- subcutaneous fat compared to wild-type but is not altered in retroperitoneal or epididymal fat. Likewise, adipocytes are significantly enlarged in GHR -/- subcutaneous adipose tissue relative wild-type mice.nd there may even be undesreibly high residues in edible tissues.

So here they are saying a lack of GH allows subcutaneous fat to go on a hypertrophy rampage.

Anyway, GH is addictive, I can tell this right now. It does make you feel REAL good. Unfortunately I have developed a bit of a problem with mine, recently when I inject, the injection site subsequently turns bright red, swells, turns into a hard lump and gets fucking itchy as hell. I know its histamine causing the itchiness, so it looks like my immune system has developed something of an immune reaction to the GH. I did some searching around and this phenomenon is somewhat common and is suppose to go away with repeated use, but this has me worried. The big itchy red lumps are very ugly.

Melanotan II

OK so ive also been on this for awhile now, the tanning has been very very mild so far, but I also haven't been getting sun. Melanotan II requires you to get at least SOME sun exposure for it to work. Fair Enough. But I have also developed some new freckles, and some existing freckles turned real dark brown. I have also experienced the other side affects, slight drop in appetite and increase libido. The inhibition of appetite is REALLY strong if you take your shot first thing in the morning.

New model for carbohydrate sensitive obesity

The carbohydrate sensitive rat as a model of obesity.    ( link here aswell )

To sum up, these guys have been working on a new model of obesity that can be induced by high-carbohyrate diets, as opposed to be bog standard high-fat diets researchers use to induce obesity in rodents. The important point here is its a model. This is EXACTLY what science is. Scientists create models in an attempt to imitate and predict the real world.

The study is already short and direct to the point so its not worth me paraphrasing it ( its free full text at moment so read it you lazy bums! ) however still I want to highlight a few key points.

The first point is that, not all rats exhibit the same propensity to develop obesity on either the high-fat or the high-carb diet. I.E. some rats just DONT get fat. This is good news for the model because this is what we have observed in humans. Some humans are clearly obesity resistant. While others are quite clearly highly prone to obesity.

BMR and TEF values did not correlate to adiposity gain during either HCD or HFD. Otherwise stated, rats with a low BMR and/or a low TEF did not exhibit any greater propensity to become obese than rats with a high BMR or TEF.

Having a higher energy expenditure does not mean you are less likely to become obese. sucks for CICO. Everytime you here someone say "he/she doesnt gain weight because they have a high metabolism", just think to yourself, thats rubbish!

Considering RQ, no relationship was observed between adiposity gain and Activity-RQ, indicating no link between substrate utilization by muscles and propensity to adiposity.

SO in this model, the fuel you burn during exercise doesnt seem to predict your obesity prone-ness

Now heres the punchline, the strongest predictor of being sensitive to carbohydrate induced obesity the researchers found was your respiratory quotient in the postprandial state.

 In general, the Rest-RQ response increased above High-Carb-Diet food quotient (FQ; 0.955) only in Carb-sensitive rats (Figure S5) which means that during this period, the proportion of fat used to fuel energy metabolism was less than the proportion of fat in the meal and was significantly higher than in CR rats between 120 and 180 minutes after ingestion of the meal.

Calculation of resting glucose and lipid oxidation (Rest-Gox and Rest-Lox) from Rest-RQ and REE showed that ingestion of the HC test-meal increased Rest-Gox and decreased Rest-Lox significantly more in CS rats

So, in this model of obesity, ( which may or may not accurately reflect human obesity ), it is the postprandial handling of the nutrients that determines if you become fat or not. ( on high-carb diet only ) If you are carbohydrate-obesity-sensitive, then what happens is when you eat carbohydrate, fat oxidation is overly suppressed. Wonder why that is? Insulin hyper-secretion?

 in Carb-Sensitive rats, already under High-Carb diet since weaning (though chow rather than the high quality synthetic HCD used during this experiment), a defective post-prandial substrate partitioning characterized by a larger post-meal increase in Rest-Glucose-oxidation and a larger post-meal inhibition of Rest-Lipid-oxidation can be considered as potentially responsible for the larger adiposity gain.

Since this observation was made early in the life of the rats, this metabolic difference can be considered as a cause rather than a consequence of sensitivity to adiposity gain under HCD 

Whoa, it almost looks like the researchers are saying that ( in this model ), your propensity to become obese on a high-carb diet is determined from birth, possibly through genetic/epigenetic factors I might guess?

This rings so painfully true for me because I was fat right from a very young age and I was raised on a high-carbohydrate diet. Lowcarb will unfortunately probably have to be a lifelong thing for me if I want to keep my weight down.

its all about the insulin!

In response to my comment on Wooo's blog about ric drasin coming out and saying that carbs determine body fatness, another bodybuilder has recently come out proclaiming the same thing, carbs/insulin play a HUGE role in body fatness.

In the video he touch's on stuff I have mentioned here previously, that the more easily and fast digesting the carb, the more fattening it is. AKA processed carbs.

Elevated fasting insulin is the cause of the obesity epidemic. I feel quite confident about this.  The postprandial insulin spikes play a role in body fatness, but I think it is the elevated fasting insulin causing the rampaging fat tsunami;s. It is the failure to expose yourself to low insulin levels, especially during the overnight fast, that results in never-ending fat accumulation.  Your suppose to properly oscillate in and out of the anabolic/catabolic states between eating and fasting.  But you never quite properly enter the catabolic state with the high fasting insulin. When you get your fasting insulin low enough, then sex steroids will determine fat deposition in the body. I also have a feeling that it is elevated fasting insulin activating aromatase constantly as to why we have so many men with gyno + low T.

So what determines fasting insulin?

No-one knows! other than the obvious fact of the recent days carbohydrate intake influencing it, the others factors involved seem to be obscure. If you search on pubmed for fasting insulin, theres very little research in this area. However we do know the GI tract plays a huge role in insulin secretion, both fasting and postprandial.

An interesting study recently came out detailing how the GI tract is reprogrammed after gastric surgery. The surgery changes the GI tract so that it itself becomes a major source for glucose disposal. More glucose disposed of in the GI tract means less hitting the bloodstream and less needing to be disposed of in adipose tissue. Will that cause weight loss?  The reprogramming of the GI tract to act as a glucose sink was initiated by exposing it to undigested nutrients.

Still further, another new study looked at lipolysis in overweight vs lean subjects. They found that overweight subjects had reduced catecholamine stimulated lipolysis. In the study they say this....

The factors regulating the expansion of human adipose are less well known.

Funny, I thought it was all about calories?

Whats the cause of this catecholamine resistance in fat people? *I think its the elevated fasting insulin*

How to reduce fasting insulin?

Well other than avoiding carbohydrate, there is one food I think actively reduces fasting insulin, sauerkraut, the combination of vinegar and fibre seems to be very potent at reducing insulin. I even think that the more sauerkraut you eat, the more weight it will force you to lose, provided you keep carbs in check.

Delta-sleep inducing peptide - FAIL?

In my on-going effort to mitigate the affects of my shift work and improve my sleep, I tried the injectable version of delta-sleep inducing peptide. Took 100mcg in the afternoon via subcutaneous injection in the belly, through an insulin needle.

I felt quite sleepy for about 2 hours after, then went back to normal. delta-sleep inducing peptide ( DSIP ) is suppose to help sleep, and especially improve slow-wave sleep. according to the literature, it doesn't matter what time of you day you take it, and its affects supposedly last for a few days after 1 injection.

Anyway, the morning after my first shot I felt quite groggy and had the classic fatigue that is associated with severely reduced REM sleep. I know when I have had reduced REM sleep because my thinking is slow and lazy, motivation to do anything is low as is general energy levels. Well so, DSIP has been a FAIL on the first night.

some info on DSIP can be found here

Melanotan II

Ive found a reputable UK source for melanotan II so im about to order some and give it a try, I am skin type 1 which means I NEVER tan naturally and only burn and peel.

Melanotan is a synthetic analogue of α-MSH, it has some side affects including increased libido and reduction in appetite. So it "may" be slightly helping for weight loss aswell. Melanotan II is also an mc4r agonist which is probably where it mediates the reduced appetite and libido side affects.

Trenbolone

An interesting video on trenbolone, what I like is the fact this guy has done the research and there are some interesting points, he explains all the in the video.

of note, his research again supports the idea of nutrient partitioning, trenbolone apparently causes massive insulin sensitivity in muscle, ( glut4 ) . This is as opposed to increased insulin sensitivity in adipose tissue, ( glut4 ), which causes fat gain.

So the point seems to be, where is the insulin sensitivity and in particular where is the glut4? That plays a big part in where your "calories" go. The same is also true for LPL. Skeletal muscle LPL protects against fat gain, while adipose LPL increases fat gain. ( link )

For the record, I dont agree with everything this guy says, im just sharing an interesting video.

Ketogenesis, & Calorie restriction increases fatty acid synthesis

Malonyl-CoA: the regulator of fatty acid synthesis and oxidation

This is a short paper on ketogenesis and is well wroth a read imo. Very accessible even to the layperson. Interestingly, the ketone acetoacetate is the preferred substrate for fuel, chosen above even glucose. The liver is the only place ketones are synthesized, and the liver itself cannot oxidize ketones, it can only release them.

I was one of the people who thought that the switch for ketogenesis was simply the depletion of oxaloacetate in the liver mitochondria, but this is not true. Apparently the signal for ketogenesis is glucagon, aswell as a decrease in Malonyl-CoA in the liver. Once the glucagon signal hits the liver, the rate-limiting step for ketogenesis is simply the amount of fats reaching the liver from the adipose tissue. The liver will burn fats and generate ketones as fast as it can.

Anyway, just read the paper. !

Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates

This is another fascinating paper, I havent seen it discussed elsewhere, if memory serves.....

The paper is another fantastic demonstration of the futility of calorie restriction in attempting to lose weight. ( although that was not the objective of the study ). Mice subjected to 30% calorie restriction achieved a lower bodyweight,

After an initial 1- to 2-wk period of weight loss, CR mice reestablish a state of energy balance in which fat mass is preserved or even increased.

The paper talks about the nutrient balancing hypothesis, and that to remain weight stable, the food quotient must match the respiratory quotient. I.E. if you eat 300g carbs and 100g fats per day, then you must also oxidize 300g of carbs and 100g of fats per day to remain weight stable. If you burnt 150g of fat per day in that example, then the theory says you would lose fat mass.

So what happened in this study was that, the 30% calorie restricted mice were only allowed to eat 92mg of fat per day, but the researchers found the mice were oxidizing 367mg of fat per day.  Thats a calorie deficit of 275mg of fat per day, so the question was, why werent the mice losing weight? Why where they weight stable? They were in calorie deficit!

Well, the researchers found that the adipose tissue ( not the liver ) of the calorie restricted mice were actually synthesizing the missing 275mg of fat per day!.

In addition, in the first 3 h postfeeding, endogenously synthesized palmitate accumulated in the subcutaneous depot five times faster in calorie restricted mice than in ad-libitum controls,

Glucose is likely the predominant substrate for FA synthesis in the adipose tissue. Consistent with adipose playing a role in FA synthesis, Wetter et al. (45) demonstrated that glucose uptake is increased in adipose tissue of calorie-restricted rats.

And this...

 immediately after food was provided, fatty-acid synthase enzyme expression increased 50-fold in calorie restricted mice, leading to values nearly threefold higher than ad-libitum controls

Anyway, as I spoke of before, calorie restriction increases AgRP, this in turn blocks MC4R signalling. Maybe whats happening is that a lack of MC4R signalling in adipose tissue leads to elevated FA synthesis in white adipocytes? Well, even if this is not the mechanism, the point remains, 30% calorie restriction increases FA synthesis in your adipocytes.

But what about 20% calorie restriction? Maybe I can lose weight there without the FA synthesis? Or 15%??

MAYBE THERES A MAGIC NUMBER THAT ALLOWS ME TO LOSE WEIGHT WITHOUT THE NEGATIVE EFFECTS OF CALORIE RESTRICTION??!?!

High glucose induces adipogenic differentiation

This is probably old news to some or most people. I myself have known for along time, just from intuitive observation of my own body, that there is something quite "fattening" about spiking your blood sugar.

High glucose induces adipogenic differentiation of muscle-derived stem cells

An In Vitro Model to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia.

Again, just the title of these studies tells you what you need to know. In the first study, high glucose concentrations induced adipocyte differentiation of stem cells from adipose tissue. ( the glucose concentration used was very high, 25mM, so take it as you will. Also was done in vitro. )

Further down in the study results we also see how high glucose even makes muscle stem cells turn into adipocytes!

The mechanism by which this seems to be happening is ROS production signalling.....

The simplest interpretation of the data are that ROS produced in response to high glucose, by stimulating PKCβ (and possibly other effectors), act as a differentiation signal for adipogenic conversion of muscle derived stem cells.

And.....

In conclusion, we demonstrate that high glucose has an adipogenic potential on stem cells derived from both the adipose tissue and skeletal muscle, and we provide some insight into the signals and molecules that underlie this process. 

I think this is part of the puzzle as to why refined carbs in particular can be so fattening. It is well documented that the digestibility of carbohydrates determines the corresponding postprandial blood sugar spike ( glycemic index ). In addition, I suppose you could say that, being insulin resistant in muscle leads to exaggerated and prolonged elevated postprandial glucose levels, and these high glucose concentrations ( could potentially ) activate adipogenic pathways, in both muscle and fat tissue.

Granted, not everyone gets massively fat from spiking their blood sugar. We know that already. Another frustrating fact we all know, is that, stopping the blood sugar spikes and removing carbs from your diet doesnt magically return you to a state of complete health and lean-ness. Its as if the damage done by the historical blood sugar spikes is permanent.  ( like maybe, getting new fat cells ) .

What is "Fat-mobilizing substance" ???

In reference to the mysterious hormone Kekwick and Pawan talked about in their 1960's era papers. Seriously, does anyone know what this is?

Best & Campbell in 1936 spoke of a substance isolated from the pituitary that would cause liver fat accumulation during fasting, while simultaneously decreasing fat contents of the fat depots ( i.e. bodyfat ).In 1947 Weil et al also confirmed the presence of a "fat mobilizing agent" isolated from the urine of a fasting rabbit, but not the normally fed rabbit.

They describe how injection of this substance caused an accumulation of liver fat at the expense of bodyfat,

A more detailed paper from Kekwick and Pawan 1960 actually goes on to describe a procedure of exactly how this substance can be isolated and extracted from the urine of fasted or carbohydrate restricted humans/animals. Upon injection of this substance, liver fat, blood lipids, and ketones all increase. Surprisingly this substance is also effective at lowering blood sugar. Furthermore, no changes in appetite or food intake accompanies this increased utilization of bodyfat from the injection of this substance.

So in essence, this substance either just straight up increases energy expenditure and/or reduces energy harvest from metabolic fuels.

Below are graphs of bodyweight of mice following injection of this substance, the substance produces a decrease in bodyweight without any significant changes in food intake.

Here is a graph when the injections are stopped after 10 days, NOTE the rapid return of bodyweight?

In the study they confirm the substance is not Corticotrophin, or Growth hormone, although it has similarities with these.

So the question is, what is this substance? Does anyone else know more about it? Has it since been proven to be a hoax?

I and others have commented on how extreme carbohydrate restriction in particular seems to produce rapid loss of bodyfat, and I cant help but wonder that in addition to reduced insulin, that this mysterious substance is also playing a role. The most shocking point is above in Fig 3, I.E. the rapid return of bodyweight after injections cease without changes in food intake. This sounds eerily like the rebound weight gain people experience after a period of lowcarbing when they try to re-introduce carbs into their diet. A re-introduction of carbs according to Kekwick and Pawan's research would shutdown production of this fat-mobilizing substance, and potentially make your regain weight, as in Fig3. with no changes in energy intake.

Thanks to Bill, I was able to get hold of the 1964 study  by Kekwick and Pawan that looked at high-fat diets in mice, at 50% calorie restriction, an 80% fat diet produced substantially more fat loss than a 80% carbohydrate diet, Kekwick and Pawan noted increased excretion of energetic metabolites on the 80% fat diet in the urine including Pyruvic acid, citric acid, and lactic acid. In general they report that urinary carbon increases in response to carbohydrate restriction, I.E. "wasting of energy".

Where fat supplies the major part of an energy deficient diet, there appears to be no attempt to utilize the diminished calorie intake more effectively in terms of supplying the organism with energy. It must therefore provide the whole of the deficiency from its own fat stores. \Vhen carbohydrate supplies the main part of a calorie deficient diet, the organism appears able to utilize the energy to better advantage and the deficiency required to be supplied from its own fat stores is less. On energy deficient diets of equal calorie value the animals are likely therefore to lose weight more rapidly when the calories are supplied in the form of fat than when they are supplied in the form of carbohydrates

One of their ideas for the increased fat loss on the high-fat diet is again the increase in this "fat-mobilizing substance" which is turn causes increased excretion of energetic metabolites in the urine.

So please, maybe someone can chime in here? Is this "fat mobilizing substance" bogus? IS there more to lowcarbing than simply a reduction in insulin?

Dont stop exercising, it makes you fat

Cessation of physical exercise changes metabolism and modifies the adipocyte cellularity of the periepididymal white adipose tissue in rats.

Im still waiting to get the full text of this study but thought id throw up the abstract. The message from this study seems to be that, if you stop exercising, you activate a lipogenic gene profile in adipocytes that seeks to fatten you up.

This lipogenic gene profile seems to go above and beyond what you would of had if you had just been sedentary and never exercised instead. So in this context it looks like, its better to not start an exercise regime at all, rather than start it then stop it later.

If you start an exercise regime, better keep it up forever!

Compared with T, the isolated adipose cells (D rats) showed a 48% increase in both basal and maximally insulin-stimulated lipogenesis

This is as I suspected previously, I.E. that the adipocyte phenotype can control its size independent of numbers calories going in the organisms mouth. ( when I say adipocyte phenotype I simply the mean particular gene expression of an individual adipocyte, and the different ratio's of receptors on its surface etc.)

Mcdonalds in London

Mcdonalds is still very popular here in the UK/london, despite the fact that the vast majority of their calories are highly processed carbohydrates.

I went to my local Mcdonalds near my work during the nightshift recently, just for a change and because I havent had it in years, and even at 9pm at night, there was a queue for the drive-thru aswell as a standing queue of people that spilled all the way out to the entrance.

Everyone "knows" Mcdonalds is unhealthy, but walk into any chain in london and youll see business is booming for them. Ironically, the majority of the people eating at Mcdonalds are slim or only slightly over-weight, and we dont judge them for eating there.. But if we spot a fat person at Mcdonalds, we are instantly like "eeh dafuq? He shouldnt be allowed to eat here!"

I think fast food in general is a booming business, fried chicken shops litter literally every street in london. There is no better business model than cheap, tasty food. The only reason these people running these shops are not making more money is because competition is fierce.

Is it complex, or not? Make up your mind.

Often when reading papers on obesity, authors will quite commonly refer to body weight regulation as "complex". They will say things like, "bodyweight is regulated by a complex system of redundant networks".  etc blah blah

Usually, they will use this type of terminology only when referring to the difficulty of producing meaningful and sustained reductions in bodyweight. Although its also used to explain why bodyweight usually returns to normal after overfeeding studies.

And yet, the very same authors will quite facilely state that obesity is "caused" by over-eating and/or sedentary behavior.

So here we are presented with something of a paradox and contradiction, because, on the one-hand, bodyweight is supposed to be complex regulated system, but, it is easily manipulated by simple CICO, by simply having a bit extra on your dinner plate, or by simply missing your morning workout, you can apparently very easily change your bodyweight.

Nothing is more simple than overeating and being lazy. But apparently  these simple actions can very easily produce large and sustained perturbations in a complex and regulated system. I.E. bodyweight.

Now, how can bodyweight be a regulated, complex  and redundant system if it can be perturbed by such simple stimuli? Doesnt that sound contradictory? Isnt the point of a complex system is that its not easily perturbed? And protected from simple stimuli producing significant changes.

The only way to solve this contradiction is that, one of the premises is wrong. Either.....

1) bodyweight is a NOT a complex regulated system, but is a simple matter of CICO

2) overeating and laziness are not CAUSES of bodyweight changes, I.E. these simple stimuli are not capable of producing significant perturbations in the complex regulated system.

So please, obesity researchers, which is it? Complex or not? Either bodyweight is a complex regulated system or its a simple CICO program.

Can you make up your mind please?











*********************

There is a possible 3rd

3) only reductions in bodyweight are part of the complex regulated system, meanwhile increases in bodyweight are a simple CICO system. If this is true, then beware, because every time you overrate a measly 5 calories, those 5 calories become a permanent addition to bodyfat!

SCFA's inhibit insulin signalling in fat cells

I havent seen this study reported anywhere else in the blogosphere!

The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43.

 Hence, this report also supports our results that suppression of adipose insulin signalling by GPR43 activation leads to prevention of obesity and improves systemic insulin sensitivity.

Look at how blasphemous this statement is, suppression of insulin signalling in adipose tissue prevents obesity.    lol  whha  ??!?!?!?!?!!!!?

Anyway, to cut a long story short, GPR43 is a receptor for short-chain fatty acids including acetate, and is expressed in various tissues including the adipocyte. There was some controversy surrounding the function of GPR43 in adipocytes because in vitro studies had shown that it promoted adipogenesis, but this research group claims to have shown that the in vitro observations of GPR43 do not match those of in vivo.

This study seems to support the nutrient partitioning idea, as GPR43 not only suppresses insulin signalling in adipocytes but improves systemic insulin signalling including in the muscle.

One observation I would like to make however, is that I have tried on numerous occasions high dose inulin for several days/weeks at a time but did not notice a reduction in fat mass.

sigh..............

More on Fat Cell dynamics, - in response to weight loss/calorie restriction

cba today so ima just copy/paste

Adaptation of human adipose tissue to hypocaloric diet

• In a study on type 2 diabetes patients submitted to 1-year dietary intervention combined with exercise, the authors stratified the adipocytes into four subfractions in respect to the cell size.16 At the end of intervention, the adipocyte size was reduced just in subfraction of ‘large’ adipocytes, while the other three remained unchanged.
• investigations suggest that individuals with hypertrophic obesity—who are at higher metabolic risk6, 18, 19, 20—are more responsive to the adipocyte size-reducing effect of hypocaloric diets in comparison with those with small adipocytes, that is, with hyperplasic obesity.
• In another study, using electron microscopy, the response was variable in a group of six patients submitted to 6 weeks’ LCD: in subjects with higher proportion of large adipocytes (hypertrophic obesity), the authors observed a shift from the fraction of large adipocytes towards the small ones, whereas in subjects with higher proportion of small adipocytes (hyperplasic obesity) no shift between the fractions occurred.
• no reduction of adipocyte size in abdominal (but not in gluteal) SCAT was found after 20 weeks’ LCD in one study.15

Lipogenesis

• insulin stimulation of de novo lipogenesis measured on isolated SCAT adipocytes was blunted after 4-weeks’ VLCD.10 However, in weight-maintenance phase, 1–3 years after initiation of the weight reducing program or after gastric banding, both, the basal- and insulin-stimulated, de novo lipogenesis measured on isolated adipocytes were increased when compared with the pre-diet condition.31

Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction.

• Many of the adipocyte abnormalities associated with obesity improve after weight loss [12–15]. Fat cell size decreases, as does basal lipolysis. Insulin and catecholamine actions are improved. However, it is not known if these actions completely return to normal. A full normalisation would suggest that the abnormalities are secondary to obesity. However, incomplete normalisation would suggest primary defects in adipocyte function that cannot be cured by weight loss
• A prominent finding in this study was a decrease in fat cell volume below the control level in weight-reduced obese subjects. Since BMI, fat distribution and body fat content were similar in obese subjects and their controls, the results imply that adipose hyperplasia (at least in abdominal subcutaneous adipose tissue) is a major feature of weight-reduced obese subjects
• This further strengthens the idea that insulin resistance is secondary to obesity, whereas adipose hypercellularity and low adipose lipolytic rates may be primary factors in obesity.
• In conclusion, adipose tissue hyperplasia (many small fat cells) is present in the weight-reduced state and probably explains the low rates of adipocyte lipolysis in this condition. However, adipocyte insulin resistance is a secondary and fully reversible phenomenon in obesity.

You cant select a random obese person from the population then tell him "fat mass is only about CICO", because you have no idea of the amount of fat cell hyperplasia they are suffering from. The more fat cells you have, the fatter youll be, BY DEFAULT.

Why am I posting this? Because I want it to be apparent that people suffering from significant hyperplasia will be unable to resolve their dysfunctional metabolism with diet and exercise alone, despite what you may hear from high standing medical doctors and bloggers. More likely we will need pharmaceutical intervention or in the worst case scenario, surgery.

How can you tell if your suffering from hyperplasia? Well, while I dont have references to back up these claims, I have several ideas. Firstly, the ease with which you rebound weight gain after weight loss will signify hyperplasia. Also the degree to which you are metabolically healthy despite significant increases in weight will signify significant hyperplasia. If you was very heavy but with no clear signs of diabetes = significant hyperplasia.

Also, just look at your fat tissue, is it very "lumpy" with lots of partitions? or is it very roundish and circular? The former = hyperplasia. See pictures in this post for example. The guy in the left most likely has significantly more hyperplasia than the right.

The dissonance of obesity

I was prompted to write this post after watching a guest video by David Pizzaro on the topic of "disgust".

He describes the emotion of disgust as a universal response, i.e. it is similarly present throughout many different culture's, and so this is good evidence that it is hardwired into our biology.

"people seem to have a natural aversion response to things that are gross, i.e. things that might contaminate us or give us diseases"

Obviously the emotion disgust has survival benefits, by making us avoid things which "disgust" us decreases our likelihood of infection. A key point here is "avoidance". Usually, "avoidance" is the primary action we take when our emotion of disgust is invoked. But there are ofcourse other actions we might take depending on how it directly affects us.

For example, imagine you wake up one morning and find a pile of dog shit right in the middle of your doorstep. What action will you take? Now ofcourse, upon first contact, your very likely to experience the emotion of disgust and your natural instinct will be to "avoid" the poop. But there is a problem, it affects you because its on YOUR doorstep. Avoiding it forever is not a viable option. So instead, you will most likely, reluctantly,  clean it up, using plastic gloves ( avoidance again ).

But now lets say one morning you wake up and find a pile of dog shit on your neighbor's doorstep. What action will you take here? It will ofcourse be complete avoidance, you certainly wouldn't clean it up for your neighbor would you? Since its not on your doorstep, it doesnt directly affect you, and so complete avoidance is likely to be the ONLY action you will take.

Anyway, cut to the chase, something which I have long noticed, and cant seem to shake, is that fat people, especially morbidly obese people, seem to invoke the disgust reflex. I cant speak for others, but when I see the severely obese people, I am revolted. This is despite every logical and rational thought telling me that these people are essentially, victims.

When I see a severely obese person in the street the first thought that comes to mind is "how could you let yourself get like that, its gross" But this is not me thinking, its not my conscious logical rational mind coming up with this, but rather this thought is coming deep from the hindbrain.

The question is, why ? WHY does obesity invoke the disgust reflex? Well, if we go back to the definition etc, we know the disgust emotion has been designed to make us avoid things that could contaminate us, infect us, or things that are likely to be diseased. In this light, it seems as if the body instinctively regards the state of obesity as one of disease. We all know that obesity reduces sexual attractiveness, being disgusted by obese people could be one way our biology protects us from mating with potentially poor gene's. 

As an example, physicians are less likely to 'Bond' with overweight patients. Why is that? Does the state of obesity in the patients subconsciously invoke the disgust reflex and subtly guide the physicians to action "avoidance" with them?

'Most' of us who has studied the subject of obesity intensely know all too well the truth. I.E. that obesity is a disease. Something about the adipose tissue has malfunctioned. The dissonance part is what I find interesting.  I.E. the dissonance between our bodies instinctively regarding obesity as a disease and the idea that "over-feeding" causes obesity.

The dissonance is that I believe that these 2 points ( i.e. obesity being a disease and simultaneously being caused by over-eating ) are evolutionary incompatible.

In an uncertain, unpredictable, and aggressive world, it should be advantageous to have access to a large of amount of calories. Having a consistent and bulky supply of nutritious food would surely be of benefit to those organisms who can access it. You might even expect this advantage to propagate and advertise itself through the organism by having the organism display a physically and sexually appealing phenotype. Afterall, we all know that emaciation is a massive sexual turn off.

And the more, the better, right? I.E. The greater the quantity of nutritious food we have access to, the more likely it is that we should survive in a harsh world. Right ? And we should advertise that increased chance of survival through consumption of that food which will gives us a physically pleasing phenotype.

But here's the paradox, because apparently, taking advantage of that large cache of food and consuming it leads ( allegedly ) to the state known as obesity, which accordingly, decreases our chance of reproduction through reduced sexual appeal, aswell as ( again, allegedly ) predisposing us to a whole host of other ailments that reduce our chance of survival.

If you believe that over-eating causes obesity, then essentially what your saying is that,  paradoxically, having access to and taking advantage of large caches of food which would normally increase an organisms survival, actually leads to a state that reduces survival and chance of gene propagation.

Having access to something which normally increases your survival, actually, decreases your survival if that something ( food ) is overindulged in.

Does that make sense?

Remember that our biology regards the state of obesity as a disease. So its almost like saying your body regards the state of having access to large quantities of food as a disease.

hhhhhhmmmmmmmm.

calorie counting is just dumb

The more I think about the idea of CICO the more I realize just how full retard it is. I mean, firstly, lets say you decide to cut your calorie intake to 1200 per day. Have you even thought about what it is exactly that your trying to achieve by doing this? You have NO IDEA what your energy expenditure is, and even if you did, the act of changing your calorie intake will change that expenditure.

This is exactly like a dog chasing its own tail going round in circles, because while your busy trying to lower your calories to decrease fat stores, your body is constantly monitoring your energy intake and adjusting your energy expenditure to match that energy intake so that fat stores are preserved and held constant.

The very moment you start consciously cutting calories, you become the dog chasing its own tail. Your chasing something which is in turn chasing you back.  Your trying to create a large gap between energy in and energy out, meanwhile your body is constantly trying to close that same gap,

Referring back to the Myths/presumptions paper on obesity, we can quite easily see why Myth #1 is false.....

Myth number 1: Small sustained changes in energy intake or expenditure will produce large, long-term weight changes.

This notion that if you over-eat 10 calories per day youll gain 1lb of fat in 350 days is completely backwards logic and putting the cart before the horse. The faulty logic is that "we need to regulate our energy intake to match our energy expenditure" to be weight stable. This is NOT how it works. This is backwards. Whats REALLY happening is that energy expenditure is constantly being tweaked to match energy intake. Its not that we have to fine tune our energy intake to match our energy expenditure over the long term to remain weight stable.

Instead, our energy expenditure is constantly being fine tuned to match energy intake over the longterm. THATS why normal lean people remain weight stable despite wild fluctuations in energy intake.

The reason it works this way is simple. Energy availability from the environment is unpredictable. The organisms body cannot force the organism to intake a certain amount of calories per day because that calorie availability is completely unknown and uncertain. Instead biology has evolved to manipulate its energy expenditure based on the energy intake the organism can achieve in that day.

To correct myth 1, it should be re-stated as....

Changes in energy expenditure will occur in response to changes in energy intake such that over the long-term energy expenditure will match energy intake..

All the evidence I have seen indicates that fat stores are the most protected commodity in the body. Long term starvation usually results in death from organ failure due to loss of lean mass, Death from starvation never results from fat mass reaching zero. I.E. , you never run out of calories. Your body values its fat stores more than the lean mass. But we also have to remember that lean mass loss in starvation is because your body is reducing energy output, like a crew on a sinking ship thats throwing stuff over-board so as to reduce its weight and keep it afloat, your body throws out stuff that contributes to energy expenditure.

I enjoyed the latest spark form Gary Taubes,  he makes the same point that many of us have been throwing around for yonks, i.e. that the overeating causes obesity type of thinking is circular logic.

Why do we get fat? Because we overeat.
How do we know we’re overeating? Because we’re getting fatter.
And why are we getting fatter? Because we’re overeating.
And so it goes, round and round.

I have argued previously that even the concept and word "overeating" is all but impossible to define. At no point can you feed someone amount of calories X and then confidently say whether or not you have "overfed" them.    This is because, the current way "overfed" is defined  is if you feed someone X amount of calories and that they gain weight from it. But it is (nigh) impossible to predict how much weight someone will gain from feeding them X calories.

Lets say I take a random person off the street, and feed them 5000 calories for the day. But thats the ONLY information I give you. How are you gonna predict if and how much weight they will gain? You cant, because I havent told you anything about the persons genetic and/or metabolic status, nor have I told you what im feeding them with. I could be feeding them with 5000 calories of doughnuts or 5000 calories of fatty meat and vegetables. Simply focusing on caloric intake alone gets you NOWHERE.

Slept well last night

Took 9mg melatonin last night about 2hrs before bed, felt drowsy within about 30 minutes then couldn't stay awake at 2hr mark. Had good deep sleep. I have noticed that I feel most refreshed when I get quality REM sleep, that is, that period near the end of sleep where your half-awake, half asleep, and also dreaming. If this final phase of sleep goes well, I just feel amazing, I get up feeling full of energy and brain works exceptionally well.

Felt a bit groggy in the morning which I know was due to the melatonin dose, but it wore off within 2 hrs. I had to take the melatonin because the Cabergoline was giving me insomnia. 2 things I have noticed about Cabergoline is that, I get severe anxiety on it, but also libido is massively increased!

Im struggling a bit with this blog at the moment, its getting harder and harder to find stuff to blog on because there are TONS of health/nutrition blogs out there. Competition for novel information is fierce. Although im not trying to turn this blog into some public guru know it all website. This place is for me to document my personal thoughts/theories aswell as information that I find valuable. Dont get me wrong, I appreciate feedback ALOT, but I want to avoid falling into the mindset of blogging to appease an audience, but instead I want to blog for myself. Then again, I dont want to blog on things that others have blogged on elsewhere, and so this further makes new content very difficult to come up with, also my occupation is not the field of nutrition/medicine so im not "in the loop".


I want to throw up some info from Dan's video here.....


22:00 minute mark

• How do we avoid making the same mistakes over and over and over again?

The idea is, that we have a natural way of looking at the information that comes at us. And when we rely on this natural way of looking at this information, there's a good chance we'll get it wrong, because our natural ways of dealing with the information can be biased. However, the question is can we get over these natural tendencies and under what conditions can we?

This reminds of the problem in Metabolic Syndrome and biased obesity research. Basically  alot of health issues are "mistakenly" attributed to as being "caused" by obesity, and I think this is happening because of how we are being fed information. Humans are massively biased towards visual information, seeing is believing.  For example, when we see an obese person, we automatically attribute all health problems that person has to their weight, because the weight is the thing we "see" has changed so dramatically from a healthy normal lean person. 

We dont "see" all the little things going on inside an obese person with metabolic syndrome, like hepatic IR, insulin hyper-secretion  + all the other biochemical changes going on. In this case it is thus very easy to fall into the trap of thinking that obesity "causes" all these health problems because the increase in bodyweight is so glaringly obvious meanwhile the biochemical changes are massively obscure and difficult to measure. 

31:00

• Should we trust our intuitions?

Our intuitions are often wrong, but also, we often dont recognize our faults. The only way to get reliable information to get the correct answer to a problem is through experimentation, measurement etc. If you want the right answer, it is best to remove all human intuition, remove all human judgement, and bias, and just follow the dots. 

For example the other day I was texting a lady friend, and I didnt get a reply. My intuition was to think, she was ignoring me, she didnt like me. Or something. Turns out that she was replying to my texts, but they got stuck in the network, and several days later I got her texts all together simultaneously ( the delayed text problem ). My intuition was wrong you see, she was not ignoring me, it was a stupid mobile phone network error that was the issue. 

I want to take this opportunity to link to another example of this. This little post by Armstrong is so true. Peoples "intuition" was wrong about 

Chernobyl. 

You have to just follow the breadcrumbs and stop trying to further theories that support what someone wants to happen. 

Also in 31:00 segment of the video Dan also talks about the best way to learn, ( which can also be ascribed to "the best way to get the right answer" )  The best way is to try lots of times, with changing different variables, and to have immediate feedback, and for that feedback to be precise.

This is a good explanation for why obesity research is a mess, and why figuring out sleep is difficult. Lots of variables, some randomness due to genetics etc. 

43:22

• Can we avoid emotional interference's in our daily decision making?

Emotions are designed to take over cognition, override "free will" in a sense. Dan says emotions are designed to aggressively take over and execute a specific sequence of events. But most importantly, he says emotions are "hard to fight"

Infact Dan then argues that trying to fight your emotions is kind of pointless. The best you can do is instead modify your situation so that you will not be put in a place where those emotions are invoked and so you do not have to fight them.

I think this bears significance for LC and dieting. If you want to avoid falling off the LC bandwagon, the best you can do is avoid situations where carby food is going to be available. I notice people often report succumbing to carbs during holidays. In these situations I dont think you should blame yourself.