Atkins fat fast is hard

Ive been toying with the Atkins fat fast protocol recently, and I must say it is far more difficult than you might realize. Even eating 2000 calories a day of mostly cream, nuts, avocado, there is an underlying perpetual hunger that calories alone cannot seem to satiate. Over the years ive become very good at recognizing the hormonal and instinctive urges my body conjures and I know what this hunger is, it is hunger for protein.

This is a very good anecdote for the "protein leverage" phenomenon which I have no doubt is absolutely true. Protein causes the release of a different set of hormones ( PYY for example ) from the intestine than fat that interacts with the vagus nerve and this is what satiates and turns off appetite.

My interest in the fat fast was rekindled after seeing this study tweeted...


Subjects were made to compare their weight loss on fasting for 10 days to eating a fat fast style diet ( 82% fat, 14% protein ) of 1000 calories for 10 days. Thats about 35g of protein per day for reference,  just slightly more than a single chicken breast.

So what happened?

The data show that the weight loss while fasting was 64.6% due to loss of lean body tissue and only 35.4% due to loss of adipose tissue. In contrast, the weight change while on the high fat diet was only 3% due to lean tissue loss and the mean total amount of body fat lost exceeded that of fasting (6.4 kg versus 3.4 kg). These results suggest that although clinically desirable weight reduction occurs during fasting, it is at the expense of lean tissue, which is physiologically undesirable.

Let me say that again, more fat is lost on 1000 cals (82% fat) per day than completely fasting. During fasting there is a disproportionate loss of lean(protein) mass,

Im not exactly sure what is going on here but I have an idea. It might be due to PPARa and hepatic amino-acid degrading enzyme ( AADE for short)

Still one of the more fascinating studies ive read comes from Semenkovich CF. , here they deleted the fatty acid synthase enzyme only in the liver,  to find some interesting results. Mice fed a zero fat diet developed hypoglycemia and when they fasted these mice they displayed characteristics equivalent to PPARa knockout mice, I.E. low ketosis and a lack of hepatic fat burning. More importantly, feeding the mice dietary fat seemed to rescue them.

The conclusions from this study are this, body fat released from adipose tissue during fasting is unable to activate PPARa in the liver, instead, a special "activator" molecule is needed that normally would be synthesized from the FAS enzyme. If you do a little digging beyond this paper you can find that one such molecule is Oleoylethanolamide. This explains why feeding the mice dietary fat also rescued them from signs of PPARa deficiency because OEA is also synthesized in the intestine from dietary fat.    

This last bolded part is probably quite important because it doesnt seem like OEA is synthesized in hardly any other tissues except liver and intestine.

Even more intriguing, a recent study has attributed some of the appetite lowering effects of gastric bypass surgery to increased synthesis of OEA in the gut.

OK OK!

so whats this got to do with the more fat loss and less lean mass lost on the fasting vs keto diet mentioned earlier?

Well.....

Hepatic Amino acid degrading enzyme is down-regulated by PPARa ( link1 , link2 ) and the second link there even mentions PPARa acting as a metabolic switch between protein burning and fat burning. Dietary protein on the other hand increases the expression of AADE, so the more protein you eat, the more you burn protein. ( and thus interrupting fat burning )

Im not sure if dietary protein directly down-regulates PPARa, but many people report lower ketosis with increasing dietary protein on a general low carb diet, so this is strong evidence that it does.

All in all, a possible contributing factor to the increased fat loss and protein sparing on a 82% fat diet compared to total fasting could be due to these interactions, I.E. unlike fasting, with dietary fat intake on the 82% fat diet there is increased synthesis of OEA ( and probably other Ethanolamide's ) in the gut which in turn helps activate PPARa . which encourages fat burning and ketosis, and lowers ADEE, which lowers protein burning. ( sparing your muscles )

Although a normal person doesnt have hepatic FAS loss and so can activate PPARa in the liver while fasting, it could well be even higher with increased OEA synthesis from the gut from dietary fat.


The last nagging point that I dont have an answer to is, why on earth is there also greater fat loss on the 1000cal diet compared to fasting?  Theres probably a whole host of reasons but it seems like consuming dietary fat ( i.e. atkins fat fast ) heavily changes your metabolism to fat burning as opposed to a mixture of protein and fat burning when fasting.

When kekwick and Pawan investigated this increased fat loss in mice their explanation was that fat was not being completely degraded to co2 before being excreted therefore reducing its caloric value.

Insulin Resistance shenanigans

IR is such a bogeyman. I am quite certain it is an effect of 99% of the things it is associated with, not a cause. Glucose disposal is usually the main proxy used to state IR.

Anyway, I thought this was interesting

A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.

As some people may be aware, a big hallmark and feature of T2D and IR is the failure of insulin to suppress hepatic glucose output during glucose ingestion. In this study they are saying subQ fat can help suppress hepatic glucose output by releasing IL6 which is downstream of cAMP in adipocytes.

We also have this study

Insulin disrupts beta-adrenergic signalling to protein kinase A in adipocytes.

So putting 2 and 2 together, what should we do to attack the IR causing us to be fat sick and diabetic?
How can we attack IR ?

By lowering insulin secretion!

it seems plausible that high ( and chronic ) insulin secretion activates PDE3B in adipocytes which degrades cAMP, causing catecholamine resistance in adipcoytes which makes you fat, but also IR through reduced IL6 levels and increased hepatic glucose output.

In theory lowering your insulin secretion should lower PDE3B in adipocytes and increase cAMP there, making you slimmer and lowering blood sugar.

This is why I think IR is the bogeyman, it is insulin secretion causing the problems. And the last thing youll probably want to do is inject yourself with more insulin to lower your blood glucose levels.

I passed my driving test ....... but im still obese!

Thanks to all the public transport links in london I havent needed to have a car or pass my driving test for quite a number of years, im now 34 and finally decided to get it done.

I took an intensive 6 day course for manual transmission and managed to pass my test on the 7th day with 6 minors. I have no prior driving experience, but my instructor was very good all credit to him.

The point being, I had to put in ALOT  of effort, skill, willpower, concentration to learn to drive and pass the test. Especially in such a short amount of time. And I managed it in 6 days.

Meanwhile, I have been trying to diet and get lean for alot longer than 6 days, infact you could say my whole life! I never been in the normal BMI category I was the fat kid at school too.

If I was too take a "dieting test" it would be fail fail fail fail x 1000000




So the question is, why is it I can do a complex willpower thing like learn to drive in such a short amount of time but keep failing miserably to get normal BMI?

The answer is because the former IS mostly under my control, and the latter is not. As much as the diet and exercise industry and guru's would like you to believe you can achieve and sustain weight loss with deliberate intervention, the reality is that you cannot, because weight is largely NOT under your control.

While operating the mechanics of a car ....is.

adipose controls appetite

Compensatory growth of adipose tissue after partial lipectomy: involvement of serum factors.

Abstract
The regulation of body weight/fat was studied by investigating mechanisms for compensatory adipose tissue growth after removal of bilateral epididymal fat pads from male adult Wistar rats. Food intake during the first 4 weeks and energy expenditure on Days 8-10 postsurgery were not different between lipectomized and sham operated rats. During Days 29-31 post surgery, a small (2.4%) but significant (P < 0.05) increase in heat production per metabolic body size was detected in lipectomized as compared with sham operated rats. The carcass composition of lipectomized and sham operated rats was not significantly different 16 weeks after surgery. The compensatory growth was fat pad-specific: mesenteric, retroperitoneal, and inguinal fat pads, but not perirenal fat pads, were heavier in lipectomized rats than in sham operated rats as early as 4 weeks postsurgery. Examination of fat cell size distribution in the compensating pads indicated a shift toward larger cells in retroperitoneal fat, but not in inguinal fat of lipectomized as compared with sham operated rats. Serum from lipectomized rats, but not media conditioned by exposure to retroperitoneal fat pads from lipectomized rats, stimulated proliferation of preadipocytes in vitro more than that from sham operated rats. Thus, compensatory adipose tissue growth after lipectomy may be mediated, in part, by blood-borne factors that are derived from tissues other than adipose tissue.


Food intake and energy expenditure measurements
focused on the early period up to 4 weeks postsurgery
and did not detect measurable increases in food intake or
decreases in energy expenditure that could account for the
lipid deposition associated with compensatory growth.

lol CICO?


Relationship of adipocyte size to hyperphagia in developing male obese Zucker rats.


Abstract
In growing male obese Zucker rats, hyperphagia reaches a maximum or "breakpoint" and declines at an earlier age with high fat than with chow-type diets. A serial adipose tissue biopsy technique was used to correlate changes of retroperitoneal adipocyte size and feeding behavior in 5- to 7-wk-old male lean and obese rats fed laboratory chow or a 35% fat diet until 30 wk of age. Although chow-fed groups had significantly greater cumulative intake, fat-fed groups had significantly greater body weight gain, retroperitoneal depot weight, and adipocyte number. Mean adipocyte size increased continuously in chow-fed groups but decreased over weeks 20-30 in fat-fed groups, reflecting increased adipocyte number. In fat-fed obese rats, hyperphagia reached a breakpoint at 11 wk and disappeared by 13 wk. In chow-fed obese rats, hyperphagia reached a breakpoint at 15-16 wk and disappeared by 19 wk. Biopsy samples revealed that adipocyte size of fat-fed obese rats was already close to maximal at 10 wk (1.12 micrograms lipid), while that of chow-fed obese rats only approached maximal at 20 wk (0.81 microgram lipid). At these time points, lipoprotein lipase activity paralleled adipocyte size. These data indicate that the duration of the growing obese rat's hyperphagia coincides with adipocyte filling and suggest the existence of feeding stimulatory and inhibitory signals from adipose tissue.


So again more evidence adipose tissue is controlling appetite and since this is in zucker rats something other than leptin is involved.

Why do obese regain weight ?

http://www.nytimes.com/2016/05/02/health/biggest-loser-weight-loss.html?_r=0

I suppose this question has been done and answered to death, including here on this blog, but theres a very very simple reason why obese people regain weight, and its EXACTLY the same reason that they got to their obese state in the first place.

I recently watched this excellent video by  Brian  who describes his theory of the "sponge syndrome" which is basically just another way of phrasing what I have been trying to say here on this blog. I.E. obesity involves recruitment of stem cells in adipose tissue called "pre-adipocytes" which morph into fully mature adipocytes and accumulate fat. And diet/exercise DOES not cause them to un-morph back into fat-less stem cell preadipocytes.

The reason reduced obese regain weight is exactly the same reason they got fat in the first place, with induction of adipogenesis in pre-adipocytes, ( adipogenesis being the phrase meaning the pathway of a pre-adipocyte morphing into an adipocyte ) the activity and load of enzymes involved in triglyceride synthesis increase massively, its been described here

When cells of the established preadipose line 3T3-L1 enter a resting state, they accumulate triglyceride and convert to adipose cells. The adipose conversion is brought about by a large increase in the rate of triglyceride synthesis

and this 

Glycerophosphate acyltransferase activity rises sharply during the conversion and reaches a level of 80 times higher than that of another 3T3 subline in which practically no adipose conversion takes place

And I blogged here about this.

So... a pre-adipocyte stores no fat....  CICO is irrelevant

Suddenly adipogenesis pathway activated, lipogenesis gene's switched on, Glycerophosphate acyltransferase activity rises, and Triglycerides accumulate........ again CICO irrelevant.

Go on a diet and exercise heavily, empty most of your fat cells to a smaller volume, but guess what, the excess adipocytes are still there, and because the excess number of adipocytes are still there.... excess amount of Glycerophosphate acyltransferase activity IS STILL THERE.

So guess what happens with time as Glycerophosphate acyltransferase activity remains elevated? Triglycerides ( fat ) accumulates again, and you regain weight.

Its really not hard at all.

P.S. I know Glycerophosphate acyltransferase is not the only enzyme involved in trig synthesis etc. Im just picking it out as an easy to understand example.

The truth about obesity - and my weight loss recommendations

Everyday I read more bullshit and stupidness from people who are suppose to be clever and well researched about obesity, including doctors and research authors themselves. Your all wrong. You dont know jack fuck shit.

Having said that, there are a handful of lab guys out there who kinda know what they are doing and it is from their studies that I have gained the most insight and formed my own conclusions.

- obesity has an extremely large genetic component, and the analogy I like to compare it to is tanning, the response to tanning is a graded scale due to genetics and MC1R polymorphism, likewise Im pretty sure the susceptibility of pre-adipocytes to differentiate into fully mature adipocytes probably also has a graded scale.

- overeating is not the "cause" of obesity, signal transduction in pre-adipocytes to differentiate and high insulin are the causes of obesity.

- obesity is basically a "growth" of the adipose tissue depot. exactly like a mole on the skin is a growth or the growth of breat tissue in males as gyno. the reason adipose depots are large and heavy and store fat is because thats what adipocytes do, their chromatin is unraveled to expose gene's that synthesize large amounts of triglyceride and package it in central lipid droplet. Uuder-eating may temporarily reduce the amount of triglyceride an adipocyte can hoard, but it wont last, the solution is to dedifferentiate or kill the adipocyte

- obesity is best thought of as a disease of excess fat retention. That last word being absolutely key.

- obesity is largely irreversible because it is a growth of the tissue, tissue growths are permanent in most cases i can think of.

- starving yourself or cutting calories is futile, neither of these mechanisms have been shown to cause adipocyte dedifferentiation or apoptosis. It will shrink adipocytes from their hypertrophic state, but that is all.

- fat people eat more because they have more adipose tissue to feed. This is back to Taubes logic and it is correct, people eat more because they are getting fat.

- fat people have higher energy expenditures because they have more tissue, and this is another reason they eat more, they are eating enough to satisfy their higher energy expenditures.

- obesity resistance is real, just like tanning resistance is real. There is no such thing as will power when  it comes to controlling eating, if you think otherwise, take a shot of GHRP6 and try to stop yourself eating.

- weight regain after dieting is the norm because the adipose tissue depot genetic profile remains intact, The size of an adipocyte is determined by the epigenetic configuration of its adipogenic gene's, such as PPARg,  glut4, caveolin-1,  SREBP1c ,   etc.  Adipocytes do not accumulate fat indefinitely, they accumulate as much as the adipogenic gene's dictate and then stop, this is why adipocytes incubated under identical cultures come out all different sizes.

- insulin causes adipocyte hypertrophy aswell as differentiation of pre-adipcoytes, this is why its the key hormone to control.

Weight loss Recommendations

Keeping in mind that weight loss is extremely difficult and maintaining that weight loss is next to impossible, but if you still want to have a go my recommendation is basically atkins with some intermittent fasting and weight lifting in the gym.

- minimize insulin secretion, low carbs but also watch the dairy, cheese , cream, butter is ok, milk and yogurt and even whey should be avoided.

- stick to whole foods with minimal processing.

- small amounts of fruit is ok, no bananas though.

- high protein, I dont recommend low protein at all even if its ketogenic, forget about ketones, the goal of fat loss is to minimize insulin signal transduction in adipocytes, this also allows higher beta-adrenergic signal transduction which is what causes the weight loss!

- protein is important for satiation, another reason to keep it high, Hungry dieters will be unsuccessful.

- intermittent fasting helps but low carbing gets your most of the way there. 8-16 is fine imo.

- try to go to the gym and lift weights, HIIT style exercise is also good.

If you stick to all these points and still find yourself fat or failing to get to your goal weight, its not your fault, you have just created so much fat tissue growth that its not reversible,  only liposuction will help.

-

Do these people need to go on a diet?

And if so, what diet should they go on? Should we fast them? starve them? low-carb them? haul them to the gym?

Also, what kind of increased fatness are they appearing to suffer from? adipocyte hypertrophy? hyperplasia? ( I suppose the one on the right is quite typical of what you would find in western women these days )

How did they get like that? Did they eat too much? Exercise too little?.......   Think about what kind of initial "intuitive"  judgement youd pass on these people.





The picture was pulled from this paper  where the subjects have a genetic condition referred to as "cohen syndrome".   But you didnt know that from just looking at the picture. I bet you just thought they ate too much , or maybe too many carbs?

What I find interesting is how they could just pass for normal random fatties by todays public standards, despite the fact the have an underlying genetic condition that makes their preadipocytes more sensitive to differentiation into mature adipocytes, they appear quite symbolic of the kind of increased fatness you can expect in "normal" people.

Even more interesting, I expect youd be less inclined to recommend "lifestyle" interventions to these people now you know they have a genetic condition, yet "lifestyle" interventions are recommended to normal obese people everyday despite the fact we are all suffering from the same condition, I.E. excess preadipcoyte recruitment. When it comes to obesity, it seems we are more inclined to prescribe treatment that is dependent on how we view the causality to have progressed.

Got fat by eating too much/exercising too little/ too much carbs? -> solution is to cut cals/carbs/exercise more! Trying fasting for a month maybe.

Got fat by having an underlying genetic condition ???? -> hmm probably need medical intervention.

Anyway I want to talk a bit more about what exactly is increased adiposity. Lately I have been reading more on adipocyte differentiation / adipogenesis, and I really feel this is primarily whats happening in all forms of obesity regardless if it is genetic or ,  :cough:,  "lifestyle" induced.

I wrote a another post on this idea here   I think theres probably a few people in the literature that also think hyperplasia is the primary thing in obesity.

Adipogenesis, the differentiation of precursor cells into mature, terminally-differentiated adipocytes, occurs throughout the human life cycle and is believed to be the primary cause of increases in body fat.*

If preadipocyte recruitment is the primary lesion in increased fatness , this ties together so many loose ends, It fits in with bauer's "lipophilia" hypothesis, and helps explain why obesity is persistent, ( dieting probably doesnt cause adipocyte de-differentiation )

Personally I think low-carbing only works to solve the adipocyte hypertrophy part of obesity, that part of your increased bodyweight that is due to insulin induced hypertrophy rapidly resolves upon low-carbing, but the part of your increased weight that comes from new pre-adipocyte differentiation is ""sticky" and doesnt resolve after lowering your insulin.**

I always make the analogy with MT2 and freakles/moles, with super levels of melanocortin receptor agonism I differentiated additional stem cells in my skin into melanocytes but they didnt go away when I stopped MT2. Similarly with super levels of insulin from carbs I differentiated additional preadipocytes into mature adipocytes that dont go away when I lowered insulin with low carb.

Is there any hope?

I remain highly pessimistic but anyway, another paper caught my eye recently.. Now I didnt know this but apparently most in vitro work on adipose study is done with newly differentiated preadipocytes, and the reason being because mature adipocytes harvested from living organisms rapidly undergo de-differentiation in cell culture.

That is, they turn back into preadipocytes and relinquish their lipid hoard ( I.E. you lose wt )  and regain their ability to differentiate into other cell types.

Since adipocytes are terminally differentiated, they can be used immediately for test purposes.6 

Several studies have been performed to establish the isolation and characterization of mature adipocytes in between the 1960s and 1990s.7–10 Since then, mature adipocytes were only rarely used, probably because of their mainly cited drawbacks such as vulnerability and dedifferentiation under in vitro conditions. 

It is well known that these cells start to dedifferentiate after 1 or 2 weeks,7,11,12 at which point, the cells reach a multivacuolar morphology while they are diminishing their cell volume.9,13 Elongated, nonlipid filled dedifferentiated fat cells (DFAT) are further able to proliferate and exhibit multilineage potential.14,15 These cells are known to express stem cell markers, such as CD73.

My earlier work on adipocyte apoptosis was probably a bit pointless now as I realize its probably not necessary to kill excess fat cells with apoptosis but rather just make them de-differentiate back into their preadipocyte non-lipid filled state.

Easier said than done though I suppose ! So the big question is if we can get fat cells to de-differentiate so easily in cell culture how can we do it in vivo and lose weight?

I dont know the answer and neither do the authors, although they mention that agents/hormones that promote lipolysis seem to be facilitating de- differentiation this is just speculation, and I'd be quite surprised if the reason adipocytes de-differentiate just because they lose lipid from increased lipolysis, and more likely the agents/hormones are causing epigenetic chromatin changes to the adipocyte gene's, re-coiling up those parts of the DNA and silencing those adipocyte markers.

adipocyte dedifferentiation in pubmed yields 141 search results. its not a well studied area, and perhaps thats why we still have an obesity epidemic.

* I need to check his references to make sure they actually support that statement

**I think its possible that some adipocytes may de-differentiate while dieting, I cant rule things out without experimental data, I think we have to assume though that most people dont experience this as when dieting they reach a plateau.