Just a quick post to summarize some of the tricks one can use to reduce postprandial glycemia and thus postprandial insulin. I would advise people to have a quick look at the links aswell.
1 ) Eat your protein and fat first, eat your carbs last. Eating your fat and protein first will slow gastric emptying ( 1, 2 ) *the other effect is ofcourse eating protein + fat with your carbs will make the chyme that passes from your stomach into your intestines less carbohydrate dense, reducing the concentration of glucose in the chyme and thereby delaying glucose absorption.
2) Vinegar is an effective way to reduce the glycemic impact of starch. Add 2 tablespoons ( 30ml ) of vinegar to your potatoes/rice, ( or sip it before the meal ) ( 3 ) Im not sure of the mechanism that vinegar helps but I think it may be due to acetic acid being converted to the short chain fatty acid acetate which in turn stimulates GLP-1. The fact that vinegar supplementation increases satiety would support that theory.
3) MSG, as recently posted, the researchers found that 2g of MSG added to a carbohydrate + protein meal significantly reduced postprandial glycemia and insulin. The mechanism is a strong increase in GLP-1 stimulated by the MSG. Enjoy a few tablespoons of soy sauce before downing the carbs.
4) Fructose, the literature indicates that small dose fructose is actually beneficial to glycemic control, with the mechanism being that fructose helps activate glucokinase. ( 4 ) The activation of this enzyme is VERY important for your glycemic control. A study has shown that the consumption of small dose fructose ( 10g ) some 30-60 mins before the carbohydrate meal reduced postprandial glycemia, while the consumption of that same fructose with the meal did not produce any significant change in glycemia. Original link from SuppVersity ( 5 )
So.... take 25g of honey 30-60 minutes before your carbohydrate meal, honey is rich in fructose and has been shown to reduce hyperglycemia in diabetic's ( 6 )
Hepatic glycolysis seems to be important in controlling body fatness, ( 7 ), this study reports that proper handling of the glycolytic enzymes helps control ( lower ) hepatic glucose production, reducing whole-body glucose disposal and therefore enhancing peripheral fatty acid oxidation since the glucose utilization in those tissue's is reduced. This ties in directly with the observed fact that people with higher 24h respiratory quotients are prone to weight gain, because higher 24h respiratory quotients indicates a higher rate of glucose oxidation compared to fat oxidation.
More research in this area is warranted.
5) Eat carbs only late afternoon / nighttime. Again as I posted on before, cortisol is very high in the hours following waking up. Hepatic glucose production will be high during this time, along with insulin resistance. BBC horizon reports that blood pressure is highest upon first waking up in the morning, blood vessels are stiffer during this time, and your blood is even more "sticky" during the morning.
They report that this time in the morning is statistically the highest time of the day for heart attacks to occur.
Let me assure you, chowing on cornflakes, orange juice and toast for breakfast is the most moronic thing you can do for your health. Nothing like spiking your blood sugar and insulin first thing in the morning when your hepatic glucose production is raging, your blood is sticky and your blood pressure is high!!!!
Diurnal Cortisol comes down in the late afternoon and evening, making you more insulin sensitive, so this is naturally the best time to eat carbs. A study has shown greater weight loss for equal calories when carbs are ingested mostly at night ( 8 )
Theres a funny fail in that BBC horizon show btw, later in the show there is some fool woman ranting about how breakfast is the most important meal of the day and is where you should get in most of your daily calories. Did she not watch the first half of the show detailing the increased blood pressure + sticky blood + cortisol? Jeeezzz.....
UPDATE(1) - Yamashita et al report that vinegar ( acetic acid ) is converted to acetate and this suppresses the transcription factor ChREBP in the liver. This is quite promising, as ChREBP is linked to fatty liver and insulin resistance.
Tuesday, 30 October 2012
Saturday, 20 October 2012
How much protein?
One thing I've quickly learned following the warrior diet is that eating enough protein is essential to surviving the 23 hour fast everyday. Those days I didnt pay attention to my protein intake and ate lots of vegetables/rice/potatoes ( which are quickly satiating in the short-term ), I experienced significantly more hunger and food obsession the following day, which starts early afternoon and continues right up until I eat at 6pm.
This heavy hunger and food obsession is absent on days where I had eaten alot of protein + fat the following evening for dinner.
Those studies claiming that boiled potato is the most "satiating" food per calorie are a fucking joke. Yeh sure, in the very immediate short-term plain boiled potato might be quite satiating, but try doing 23/1 IF while relying on that short-term signal from potatoes.
Aint happening dude.
Anyway, I just wanted to dust off this study where the researchers were looking for how protein inhibits AgRP. The graph that most caught my attention in the study was this one.......Rats fed either 10% or 20% protein diet...................
While I cant make any definite conclusions from this graph about exactly how much protein one should eat, what we can certainly say is that 10% protein is probably not enough, as 20% protein greatly suppresses AgRP. As noted by the researchers, low-protein diets increase food intake. ( The researchers also go on to show that it is leucine that has the big affect on suppressing AgRP )
Recall that AgRP is a starvation neuropeptide, it reduces energy expenditure by blocking MC4R signal transduction, it also increases hunger and even reduces fertility ( as evidenced that ob/ob leptin deficient mice have fertility restored if you also knock-out AgRP. )
So if im eating 2500 calories per day, 20% protein means I need to get atleast 125g of protein per day. This fits in with my personal experience quite well, as I have observed I need about 125-150g of protein per day to feel "properly" satiated.
Would there be additional reductions in AgRP if we increased protein to 25% or 30%? Probably, but I suspect it would be subject to severe diminishing returns. From the evidence we have here, its probably best not to let your protein intake drop below 20%. I personally prefer around 25%.
This heavy hunger and food obsession is absent on days where I had eaten alot of protein + fat the following evening for dinner.
Those studies claiming that boiled potato is the most "satiating" food per calorie are a fucking joke. Yeh sure, in the very immediate short-term plain boiled potato might be quite satiating, but try doing 23/1 IF while relying on that short-term signal from potatoes.
Aint happening dude.
Anyway, I just wanted to dust off this study where the researchers were looking for how protein inhibits AgRP. The graph that most caught my attention in the study was this one.......Rats fed either 10% or 20% protein diet...................
While I cant make any definite conclusions from this graph about exactly how much protein one should eat, what we can certainly say is that 10% protein is probably not enough, as 20% protein greatly suppresses AgRP. As noted by the researchers, low-protein diets increase food intake. ( The researchers also go on to show that it is leucine that has the big affect on suppressing AgRP )
Recall that AgRP is a starvation neuropeptide, it reduces energy expenditure by blocking MC4R signal transduction, it also increases hunger and even reduces fertility ( as evidenced that ob/ob leptin deficient mice have fertility restored if you also knock-out AgRP. )
So if im eating 2500 calories per day, 20% protein means I need to get atleast 125g of protein per day. This fits in with my personal experience quite well, as I have observed I need about 125-150g of protein per day to feel "properly" satiated.
Would there be additional reductions in AgRP if we increased protein to 25% or 30%? Probably, but I suspect it would be subject to severe diminishing returns. From the evidence we have here, its probably best not to let your protein intake drop below 20%. I personally prefer around 25%.
Wednesday, 17 October 2012
Too many fat cells
This post from suppveristy clearly explains the problem better than I.
Adipocyte hyperplasia is THE problem why obesity is almost impossible to manage with dietary intervention. The below picture shows the leptin secretion of a fat cell in relation to its volume, the relationship in non-linear, small type I fat cells secrete 200 leptin, while larger type II fat cells secrete 7 times as much leptin, 1400.
.jpg)
Because of the negative feedback loop inherent to all adipocytes that their insulin sensitivity varies with their volume, you will find that adipocytes in the same region of the body are approximately of equal volume. Spreading your bodyfat out over many adipocytes will severely compromise your leptin output. This is why dieted down people have reduced energy expenditure because for a given bodyweight they are leptin insufficient.
Why do weight loss stalls happen? Because you have reached a point where you have reduced adipocyte volume enough to be in balance with 24hour insulin secretion. To continue weight loss some adipocyte apoptosis is probably necessary.
Now we know why overfeeding studies fail to generate the obesity phenotype, because the overfeeding may not be enough to produce the sufficient adipocyte hyperplasia. If during overfeeding all you do is increase adipocyte volume, these stuffed fat cells will become increasingly insulin resistant and leak FFA, increasing energy expenditure ( or increasing ectopic fat accumulation ) until their volume decreases enough to become insulin sensitive again to be in balance with 24hour insulin secretion.
Whats the cause of the obesity epidemic? I think its as simple as this......
Foods high in glycemic index + glycemic load -> explosive insulin secretion -> adipocyte multiplication!
No need to talk about "calories"!
Spreadbury's Carbohydrate density graph is a correct illustration of the "causes" of the problem, but I think he has the wrong hypothesis, it is not leptin resistance, Rice cake diet anyone?
Adipocyte hyperplasia is THE problem why obesity is almost impossible to manage with dietary intervention. The below picture shows the leptin secretion of a fat cell in relation to its volume, the relationship in non-linear, small type I fat cells secrete 200 leptin, while larger type II fat cells secrete 7 times as much leptin, 1400.
.jpg)
Because of the negative feedback loop inherent to all adipocytes that their insulin sensitivity varies with their volume, you will find that adipocytes in the same region of the body are approximately of equal volume. Spreading your bodyfat out over many adipocytes will severely compromise your leptin output. This is why dieted down people have reduced energy expenditure because for a given bodyweight they are leptin insufficient.
Why do weight loss stalls happen? Because you have reached a point where you have reduced adipocyte volume enough to be in balance with 24hour insulin secretion. To continue weight loss some adipocyte apoptosis is probably necessary.
Now we know why overfeeding studies fail to generate the obesity phenotype, because the overfeeding may not be enough to produce the sufficient adipocyte hyperplasia. If during overfeeding all you do is increase adipocyte volume, these stuffed fat cells will become increasingly insulin resistant and leak FFA, increasing energy expenditure ( or increasing ectopic fat accumulation ) until their volume decreases enough to become insulin sensitive again to be in balance with 24hour insulin secretion.
Whats the cause of the obesity epidemic? I think its as simple as this......
Foods high in glycemic index + glycemic load -> explosive insulin secretion -> adipocyte multiplication!
No need to talk about "calories"!
Spreadbury's Carbohydrate density graph is a correct illustration of the "causes" of the problem, but I think he has the wrong hypothesis, it is not leptin resistance, Rice cake diet anyone?
Monday, 15 October 2012
Starvation induced apoptosis
In the last post I made the claim that fasting and/or very low calorie diet was necessary for starting the apoptosis cascade. For some reason, low insulin does not in itself seem to be enough, otherwise we would expect ketogenic diet's to completely demolish bodyfat. But alot of people easily become weight stable on ketogenic diets, even at still elevated levels of adiposity ( I.E. famous weight loss stall ).
Perhaps part of the reason for this is that GLP-1 signalling in adipocytes also inhibits apoptosis. So even if you achieve very low insulin with ketogenic dieting, you will still inhibit apoptosis because with every meal you eat, you secrete GLP-1. I can't help but wonder if this is partly behind the reason why weight regain is so aggressive after cessation of low-carb dieting and trying to introduce carbs back onto the menu.
The low-carb dieting would likely favour reductions in adipocyte volume and perturb adipocyte apoptosis through continued GLP-1 secretion in response to meals.
There doesnt seem to be any easy way of getting rid of adipocyte over-growth sadly.
Something which has confused researchers for sometime is how shooting a bolus dose of leptin into the brain causes deletion of adipocytes by apoptosis. ( 1 )
Now that my understanding is more up to date, I expect the reason this is happening is because a sudden dose of leptin in the brain causes a sudden surge in sympathetic nervous system stimulation of lipolysis in adipocytes, leading to a surge in beta-oxidation and ROS production. This in turn, can induce apoptosis. ( 2 )
Perhaps part of the reason for this is that GLP-1 signalling in adipocytes also inhibits apoptosis. So even if you achieve very low insulin with ketogenic dieting, you will still inhibit apoptosis because with every meal you eat, you secrete GLP-1. I can't help but wonder if this is partly behind the reason why weight regain is so aggressive after cessation of low-carb dieting and trying to introduce carbs back onto the menu.
The low-carb dieting would likely favour reductions in adipocyte volume and perturb adipocyte apoptosis through continued GLP-1 secretion in response to meals.
There doesnt seem to be any easy way of getting rid of adipocyte over-growth sadly.
Something which has confused researchers for sometime is how shooting a bolus dose of leptin into the brain causes deletion of adipocytes by apoptosis. ( 1 )
Now that my understanding is more up to date, I expect the reason this is happening is because a sudden dose of leptin in the brain causes a sudden surge in sympathetic nervous system stimulation of lipolysis in adipocytes, leading to a surge in beta-oxidation and ROS production. This in turn, can induce apoptosis. ( 2 )
Saturday, 13 October 2012
Is Starvation the cure to obesity?
Im sure there are many people who would like you to believe this. Something to do with "negative energy balance" im sure they would say, displaying complete ignorance for the fact that biology employees countless homoeostatic feedback loops to keep certain parameters within a tight range.
Myself, I hate calorie restriction, it is nothing but misery and torture. Infact, I would rather straight up fast than subject myself to the inhuman suffering of eating less than what I feel like I want to.
When I eat, I want to continue eating until I get complete satisfaction, until my body naturally tells me ive had enough. I cant just eat a small meal for lunch, eating in this way just makes me MORE hungry. Im pretty sure now, I know why that is....... ( i.e. inhibition of hepatic fatty acid oxidation without the corresponding incretin secretion to offset the hunger ).
Do not under-estimate the contribution of hepatic fatty acid oxidation to whole body energy expenditure, even if organ mass makes up only 5–6% of body mass, it accounts for almost 80% of resting energy expenditure ( 1 ), Contrast this to muscle, which most people says keeps you lean, but according to Mark Sisson, a pound of muscle, at rest, burns about six calories per day. ( 2 )
Instead I expect the way that muscle helps keep you lean is because it helps improve nutrient partitioning towards there and away from adipose tissue by increasing insulin sensitivity and allowing more glucose/GLUT4 disposal in muscle, probably in the same sense that skeletal muscle LPL protects you from fat gain ( 3 )
Anyway,
I want to make a somewhat outrageous speculation that starvation "might" atleast in part be the cure to obesity.
First note, that obesity tends to involve more adipocyte multiplication/differentiation, rather than just an increase in adipocyte volume. ( 4 ) I.e. Fat tissue growth. This is what Thiazolidinediones do, and how they make you fat, new fat cells are born and because the are small, they are exquisitely insulin sensitive. I hope I dont need to convince anyone that adipocyte insulin sensitivity is a determinant of how big it can get......
OK
Something we also know is that weight loss typically only involves reductions in adipocyte volume, not number, a drop in volume makes the adipocytes more insulin sensitive, and thus make you prone to weight gain. Despite all the complications in trying to find out why dieted down people regain weight so easily, I expect the answer to be as simple as this. i.e. a failure to reduce adipocyte number.
Consider the example...
Bob = 15% body fat, 500 adipocytes
Joe = 15% body fat, 1000 adipocytes
In this scenario, both joe and bob are just as fat as each other, by definition their adipose tissue is 15% of mass. Since bob has less adipocytes, it must follow that bob stores MORE TOTAL fat in each of his adipocytes. ( we have to also accept the pre-condition that in general, fat mass is dividend evenly between adipocytes, I.E. We dont store all our 15% fat in our belly and thighs. But the 15% is distributed over the entire body. )
Adipocytes that store more total fat are larger in circumference and so are less insulin sensitive.
Meanwhile joe will store less total fat mass in each of his adipocytes, meaning their circumference will be smaller and therefore meaning they will be more insulin sensitive. Joe will thus be more vulnerable to weight gain.
So a person who has lost weight, in the typical fashion of calorie restriction, can be just as thin as a lean person, but will probably have more total adipocytes, because as we just agreed, weight loss usually only involves reductions in adipocyte volume, not number. A tell tail sign of this is leptin. If your just as thin as someone else, but have less leptin, its most likely because you have more fat cells. Thats why Thiazolidinediones are reported to either leave leptin unchanged or DECREASE leptin, because Thiazolidinediones increase fat cell number.
Reversing obesity is all about reducing your adipocyte number, in addition to their size.
Short of surgical intervention to remove the excess fat cells, is there anything else that can be done? What about adipocyte apoptosis?
OK this is where my speculation gets outrageous, I wouldnt want to get anyone's hope up falsely! zomg!
A curious case of the man who fasted for 1 year ( 5 ), but what is most impressive, is that he only gained back 16 lbs after he stopped dieting. I dont know if he had any kind of surgery, or if he had just hulk like willpower, but I was intrigued after reading also this study ( 6 ). It talks about a protein called CIDEA.
Apparently, CIDEA is involved in adipocyte apoptosis, and is negatively regulated by insulin. Starving fat cells and exposing them to very ( VERY ) low levels of insulin seems to induce, or rather, "allow" apoptosis. To quote....
The adipocytes were incubated with or without insulin, and without insulin they started to self-destruct, this is because without insulin, adipocyte CIDEA starts to increase.
So my question is this, did the complete starvation in the 1-year man allow significant adipocyte apoptosis and thus inhibit his potential weight regain? Now, im not suggesting that you need to completely fast from food until you reach your goal weight.
Instead, what im thinking is that short bursts of fasting, perhaps 48-72 hours, could possibly enhance adipocyte apoptosis. And adipocyte apoptosis is absolutely necessary for "curing" obesity. Ofcourse at this moment in time, I dont have any in vivo evidence of this. Extrapolating from cell culture to in vivo has many flaws, not least of which is that nobody has zero insulin, even when fasting. But complete fasting is one of the few ways to get insulin to its lowest.
At this point, its worth remembering that Peter thinks that obesity can result from a failure to generate superoxide in adipose tissue, I.E. from a failure to make adipocytes insulin resistant. Mice that are deficient in NADPH oxidase 4 ( NOX4 ) in adipose tissue display increased susceptibility to obesity. What does NOX4 do? It is involved in the generation of superoxide. NOX4-derived ROS is a key modulator of adipocyte differentiation and mediates insulin receptor signaling in mature adipocytes in vitro.
Obesity in NOX4 deficient mice results from accelerated adipocyte differentiation and hypertrophy, and an increase in whole body energy efficiency.
Bingo!
So reduced superoxide in adipocytes leads to them multiplying and growing faster. But why am I talking about this? Is there a connection with CIDEA?
Besides the point that genetic Polymorphism in CIDEA is associated with obesity, Another team of researchers had a very interesting hypothesis, that CIDEA regulates fatty acid oxidation in adipocytes. And we know that fatty acid oxidation in adipocytes produces superoxide, making adipocytes insulin resistant and protecting us from obesity. Further the researchers speculate that it is calorie restriction per se, that increases CIDEA.
The last link in the chain is if there is a connection between superoxide production and apoptosis. And I think the answer to this question could be yes, anti-HIV drugs are associated with lipodystrophy, and there are also associated with oxidative stress and ROS. This study reports that anti-HIV drugs increase oxidative stress and subsequently overwhelm antioxidant capacity and that this can lead to apoptosis.
Summary :-
For the TL:DR newbs, here is my theory..( its just a theory, I welcome criticism/feedback )
1) Fasting ( or SEVERE calorie restriction ) leads to increased CIDEA in adipocytes.
2) Increased lipolysis occurs along with increased fatty acid oxidation actually inside the adipocyte
3) Generation of oxidative stress and superoxide, leading to insulin resistance in adipocyte
4) Adipocyte insulin resistance along with low insulin from fasting leads to complete insulin insufficiency in adipocytes
5) Blindless to insulin removes protection of insulin mediated anti-apoptosis. ( i.e. insulin protects adipocytes from apoptosis )
6) Superoxide production overwhelms antioxidant capacity, eventually leading to apoptosis.
Myself, I hate calorie restriction, it is nothing but misery and torture. Infact, I would rather straight up fast than subject myself to the inhuman suffering of eating less than what I feel like I want to.
When I eat, I want to continue eating until I get complete satisfaction, until my body naturally tells me ive had enough. I cant just eat a small meal for lunch, eating in this way just makes me MORE hungry. Im pretty sure now, I know why that is....... ( i.e. inhibition of hepatic fatty acid oxidation without the corresponding incretin secretion to offset the hunger ).
Do not under-estimate the contribution of hepatic fatty acid oxidation to whole body energy expenditure, even if organ mass makes up only 5–6% of body mass, it accounts for almost 80% of resting energy expenditure ( 1 ), Contrast this to muscle, which most people says keeps you lean, but according to Mark Sisson, a pound of muscle, at rest, burns about six calories per day. ( 2 )
Instead I expect the way that muscle helps keep you lean is because it helps improve nutrient partitioning towards there and away from adipose tissue by increasing insulin sensitivity and allowing more glucose/GLUT4 disposal in muscle, probably in the same sense that skeletal muscle LPL protects you from fat gain ( 3 )
Anyway,
I want to make a somewhat outrageous speculation that starvation "might" atleast in part be the cure to obesity.
First note, that obesity tends to involve more adipocyte multiplication/differentiation, rather than just an increase in adipocyte volume. ( 4 ) I.e. Fat tissue growth. This is what Thiazolidinediones do, and how they make you fat, new fat cells are born and because the are small, they are exquisitely insulin sensitive. I hope I dont need to convince anyone that adipocyte insulin sensitivity is a determinant of how big it can get......
OK
Something we also know is that weight loss typically only involves reductions in adipocyte volume, not number, a drop in volume makes the adipocytes more insulin sensitive, and thus make you prone to weight gain. Despite all the complications in trying to find out why dieted down people regain weight so easily, I expect the answer to be as simple as this. i.e. a failure to reduce adipocyte number.
Consider the example...
Bob = 15% body fat, 500 adipocytes
Joe = 15% body fat, 1000 adipocytes
In this scenario, both joe and bob are just as fat as each other, by definition their adipose tissue is 15% of mass. Since bob has less adipocytes, it must follow that bob stores MORE TOTAL fat in each of his adipocytes. ( we have to also accept the pre-condition that in general, fat mass is dividend evenly between adipocytes, I.E. We dont store all our 15% fat in our belly and thighs. But the 15% is distributed over the entire body. )
Adipocytes that store more total fat are larger in circumference and so are less insulin sensitive.
Meanwhile joe will store less total fat mass in each of his adipocytes, meaning their circumference will be smaller and therefore meaning they will be more insulin sensitive. Joe will thus be more vulnerable to weight gain.
So a person who has lost weight, in the typical fashion of calorie restriction, can be just as thin as a lean person, but will probably have more total adipocytes, because as we just agreed, weight loss usually only involves reductions in adipocyte volume, not number. A tell tail sign of this is leptin. If your just as thin as someone else, but have less leptin, its most likely because you have more fat cells. Thats why Thiazolidinediones are reported to either leave leptin unchanged or DECREASE leptin, because Thiazolidinediones increase fat cell number.
Reversing obesity is all about reducing your adipocyte number, in addition to their size.
Short of surgical intervention to remove the excess fat cells, is there anything else that can be done? What about adipocyte apoptosis?
OK this is where my speculation gets outrageous, I wouldnt want to get anyone's hope up falsely! zomg!
A curious case of the man who fasted for 1 year ( 5 ), but what is most impressive, is that he only gained back 16 lbs after he stopped dieting. I dont know if he had any kind of surgery, or if he had just hulk like willpower, but I was intrigued after reading also this study ( 6 ). It talks about a protein called CIDEA.
Apparently, CIDEA is involved in adipocyte apoptosis, and is negatively regulated by insulin. Starving fat cells and exposing them to very ( VERY ) low levels of insulin seems to induce, or rather, "allow" apoptosis. To quote....
After starvation for 72 h, numbers of adipocytes were decreased by 18.0 ± 7.7% and 6.6 ± 0.6% of adipocytes were TUNEL-positive
The adipocytes were incubated with or without insulin, and without insulin they started to self-destruct, this is because without insulin, adipocyte CIDEA starts to increase.
So my question is this, did the complete starvation in the 1-year man allow significant adipocyte apoptosis and thus inhibit his potential weight regain? Now, im not suggesting that you need to completely fast from food until you reach your goal weight.
Instead, what im thinking is that short bursts of fasting, perhaps 48-72 hours, could possibly enhance adipocyte apoptosis. And adipocyte apoptosis is absolutely necessary for "curing" obesity. Ofcourse at this moment in time, I dont have any in vivo evidence of this. Extrapolating from cell culture to in vivo has many flaws, not least of which is that nobody has zero insulin, even when fasting. But complete fasting is one of the few ways to get insulin to its lowest.
At this point, its worth remembering that Peter thinks that obesity can result from a failure to generate superoxide in adipose tissue, I.E. from a failure to make adipocytes insulin resistant. Mice that are deficient in NADPH oxidase 4 ( NOX4 ) in adipose tissue display increased susceptibility to obesity. What does NOX4 do? It is involved in the generation of superoxide. NOX4-derived ROS is a key modulator of adipocyte differentiation and mediates insulin receptor signaling in mature adipocytes in vitro.
Obesity in NOX4 deficient mice results from accelerated adipocyte differentiation and hypertrophy, and an increase in whole body energy efficiency.
Bingo!
So reduced superoxide in adipocytes leads to them multiplying and growing faster. But why am I talking about this? Is there a connection with CIDEA?
Besides the point that genetic Polymorphism in CIDEA is associated with obesity, Another team of researchers had a very interesting hypothesis, that CIDEA regulates fatty acid oxidation in adipocytes. And we know that fatty acid oxidation in adipocytes produces superoxide, making adipocytes insulin resistant and protecting us from obesity. Further the researchers speculate that it is calorie restriction per se, that increases CIDEA.
The last link in the chain is if there is a connection between superoxide production and apoptosis. And I think the answer to this question could be yes, anti-HIV drugs are associated with lipodystrophy, and there are also associated with oxidative stress and ROS. This study reports that anti-HIV drugs increase oxidative stress and subsequently overwhelm antioxidant capacity and that this can lead to apoptosis.
Summary :-
For the TL:DR newbs, here is my theory..( its just a theory, I welcome criticism/feedback )
1) Fasting ( or SEVERE calorie restriction ) leads to increased CIDEA in adipocytes.
2) Increased lipolysis occurs along with increased fatty acid oxidation actually inside the adipocyte
3) Generation of oxidative stress and superoxide, leading to insulin resistance in adipocyte
4) Adipocyte insulin resistance along with low insulin from fasting leads to complete insulin insufficiency in adipocytes
5) Blindless to insulin removes protection of insulin mediated anti-apoptosis. ( i.e. insulin protects adipocytes from apoptosis )
6) Superoxide production overwhelms antioxidant capacity, eventually leading to apoptosis.
Monday, 8 October 2012
Overfeeding does not imitate obesity + Diet Update
One of the more common arguments we often see is that "over-eating" causes obesity by the mechanism of "positive energy balance", and part of the evidence for this is overfeeding studies, whereby we force feed animals or humans extra calories, and lo and behold, they gain fat mass and become "obese".
Or do they?
Do they really become obese?
Well, that really depends on how exactly you define "obesity". One of the most important characteristics of obesity, in addition to the obvious elevation in fat mass, is that this elevated fat mass is homoeostatically defended against by the body. Obesity is MORE than just a simple increase in fat mass. This is why overfeeding does not imitate obesity, because although we can successfully elevate the fat mass of organisms by overfeeding them, that elevated level of fat mass is NOT defended against. Instead, the organism easily returns to their original weight once the over-feeding ends.
This really is a critical distinction that is often overlooked in obesity discussions, and is exactly why obesity should be treated as a disease.
This paper is where I got this argument from, the paper also has many other interesting observations about the misconceptions of obesity, if you click on the PDF link its free access, the paper is not at all technical and is very accessible to the lay-person.
Diet Update
So ive been on the warrior diet ( 23/1 IF ) for 3 weeks now, and I think its going well. Lost about 6lbs so far, not amazing, I know I would of lost significantly more if I had been strict ketogenic but the advantage is that currently im not restricting any food groups and as such the diet is more sustainable. Im doing about 50/50 high-carb to low-carb days, the fact that ive lost weight while eating in excess of 2500 calories per day is especially motivating.
This is the longest ive ever been on 23/1 IF, in the past I tried to do it with strict low-carb but I always fell off the wagon because combining low-carb with 23/1 was too restrictive. Maybe its time for me to finally accept that I cant do low-carb for life, ive been on and off low-carb for the last 10 years because I cant sustain it longterm. Although I still gain weight easily from carbs, my weight is far more manageable doing intermittent fasting.
Im amazed at how the diet has changed my feelings towards food. I no longer get any sort of food cravings, the desire to eat during the day has waned greatly, the desire to eat for pleasure, to eat out of boredom etc those feelings towards food have completely vanished. Now I eat to satisfy hunger, and it feels great.
Sometimes I get very heavy hunger pangs around lunchtime, 2pm, but it quickly goes away within 30 minutes if you can resist it. Alternatively I can just take 25g of coconut oil and the hunger will go away. Coconut oil will not take you out of the fasting state because the short and medium chain fats directly enhance liver fat oxidation.
I eat my meal between 5pm-8pm everyday, I make sure its always high protein, something like 120g, eating low protein makes it very hard to do the 23hour fast. If I dont feel im going to get enough protein from the meal I supplement 60g of whey. Despite whey being highly insulinogenic, it seems to be very favourable for body composition ( 1, 2 ), in the past I had thought of whey as just a gimmick, but there is some science to back it up.
Something else that seems to be important is the order of eating, I feel much better if I eat the carbs AFTER the protein + fat. If I eat the carbs first it takes more food to satiate me and I feel more hungry the next day. My first impression is that the protein + fat first delays gastric emptying and potentially lowers the glycemic index of the carbs.
A big disadvantage to this style of eating is the large meals at night can completely sedate you, youll be lying on the couch / bed for 2 hours after eating waiting for the food digest and your big stomach to shrink.
Or do they?
Do they really become obese?
Well, that really depends on how exactly you define "obesity". One of the most important characteristics of obesity, in addition to the obvious elevation in fat mass, is that this elevated fat mass is homoeostatically defended against by the body. Obesity is MORE than just a simple increase in fat mass. This is why overfeeding does not imitate obesity, because although we can successfully elevate the fat mass of organisms by overfeeding them, that elevated level of fat mass is NOT defended against. Instead, the organism easily returns to their original weight once the over-feeding ends.
This really is a critical distinction that is often overlooked in obesity discussions, and is exactly why obesity should be treated as a disease.
This paper is where I got this argument from, the paper also has many other interesting observations about the misconceptions of obesity, if you click on the PDF link its free access, the paper is not at all technical and is very accessible to the lay-person.
Diet Update
So ive been on the warrior diet ( 23/1 IF ) for 3 weeks now, and I think its going well. Lost about 6lbs so far, not amazing, I know I would of lost significantly more if I had been strict ketogenic but the advantage is that currently im not restricting any food groups and as such the diet is more sustainable. Im doing about 50/50 high-carb to low-carb days, the fact that ive lost weight while eating in excess of 2500 calories per day is especially motivating.
This is the longest ive ever been on 23/1 IF, in the past I tried to do it with strict low-carb but I always fell off the wagon because combining low-carb with 23/1 was too restrictive. Maybe its time for me to finally accept that I cant do low-carb for life, ive been on and off low-carb for the last 10 years because I cant sustain it longterm. Although I still gain weight easily from carbs, my weight is far more manageable doing intermittent fasting.
Im amazed at how the diet has changed my feelings towards food. I no longer get any sort of food cravings, the desire to eat during the day has waned greatly, the desire to eat for pleasure, to eat out of boredom etc those feelings towards food have completely vanished. Now I eat to satisfy hunger, and it feels great.
Sometimes I get very heavy hunger pangs around lunchtime, 2pm, but it quickly goes away within 30 minutes if you can resist it. Alternatively I can just take 25g of coconut oil and the hunger will go away. Coconut oil will not take you out of the fasting state because the short and medium chain fats directly enhance liver fat oxidation.
I eat my meal between 5pm-8pm everyday, I make sure its always high protein, something like 120g, eating low protein makes it very hard to do the 23hour fast. If I dont feel im going to get enough protein from the meal I supplement 60g of whey. Despite whey being highly insulinogenic, it seems to be very favourable for body composition ( 1, 2 ), in the past I had thought of whey as just a gimmick, but there is some science to back it up.
Something else that seems to be important is the order of eating, I feel much better if I eat the carbs AFTER the protein + fat. If I eat the carbs first it takes more food to satiate me and I feel more hungry the next day. My first impression is that the protein + fat first delays gastric emptying and potentially lowers the glycemic index of the carbs.
A big disadvantage to this style of eating is the large meals at night can completely sedate you, youll be lying on the couch / bed for 2 hours after eating waiting for the food digest and your big stomach to shrink.
Thursday, 4 October 2012
Viagra for shift-work?
Well well, wonders never cease, I read a curious article today about how Viagra can actually help circadian phase shift advancement ( recall that advancing the circadian rhythm is substantially harder than delaying it ) , and was lead to this study
I love self experimentation, so now I just gotta pluck up the balls to go into my local boots store and get some. I think Ill use it in the morning right when im advancing the circadian rhythm with the light box.
In other news, im contemplating getting a Vitamin D lamp.
I love self experimentation, so now I just gotta pluck up the balls to go into my local boots store and get some. I think Ill use it in the morning right when im advancing the circadian rhythm with the light box.
In other news, im contemplating getting a Vitamin D lamp.
Subscribe to:
Posts (Atom)