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.
Tuesday, 16 August 2016
Monday, 30 May 2016
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.
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.
Sunday, 29 May 2016
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.
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.
Thursday, 12 May 2016
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
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.
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 synthesisand 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.
Sunday, 1 May 2016
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.
-
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.
-
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