Insulin and obesity?

Alan Aragon and I have had this conversation a couple of times over the last week and it’s funny that all the experts that blame obesity on elevated insulin levels alone have obviously not looked at the Primary Scientific data as it indicates different. Insulin plays numerous roles in metabolism. Popular diet gurus generally have no idea of the complexity and various effects insulin cause in the body.



From Popular diets: Scientific Review Freedman et al.

Energy restriction, independent of diet composition (e.g., 15% to 73% CHO) improves glycemic control. The ability to lose weight on a calorie restricted diet over a short term period does not vary in obese healthy women as a function of insulin resistance or hyperinsulinemia. Golay et al. reported subjects consuming isocaloric diets (1000 kcal) containing 15% CHO had significantly lower insulin levels as compared with those consuming 45% CHO, yet there was no difference in weight loss between the two groups.

Grey and Kipnis studied 10 obese patients who were fed hypocaloric (1500 kcal/d) liquid-formula diets containing either 72% or 0% CHO for 4 weeks before switching to the other diet. A significant reduction in basal plasma insulin levels was noted when subjects ingested the hypo caloric formula devoid of CHO. Refeeding the hypocaloric, high CHO formula resulted in a marked increase in the basal plasma insulin. However, patients lost 0.75 to 2.0 kg/wk irrespective of caloric distribution.

The role of insulin in the synthesis and storage of fat has obscured its important effects in the central nervous system, where it acts to prevent weight gain, and has led to the misconception that insulin causes obesity. It has recently been shown that selective genetic disruption of insulin signaling in the brain leads to increased food intake and obesity in animals demonstrating that intact insulin signaling in the central nervous system is required for normal body weight regulation.

In my new book I do an extensive key point review of this paper


It should also be noted that hyper insulin sensitivity has been identified as a powerful predictor of weight gain

Also as pointed out above effects on the CNS include reduced food intake as Leptin levels increase (energy expenditure increases, energy intake decreases)

Study be Schwartz Reduced Insulin Secretion: an independent predictor of bdwt gain
Concluded IR and Hyerinsulinemia were not causal factors of obesity

Tons and tons of research the challenges the catch all-phrase “high insulin levels cause obesity”

As I have mentioned often what about ASP powerful stimulator triglyceride


Look at the Primary Research Data it is interesting and challenges much of the much perpetuated information concerning insulin

Thanks

Coach Hale
www.maxcondition.com

I thought i would bump this to the top as there seems to be a over emphasis on insulin causing obesity again

Gary Taubes is wrong


thanks,
coach hale
www.maxcondition.com

But surely glucose levels, and the types of carbohydrates that give rise to glucose levels, matter.

And aren't there studies that do show a difference when macronutrient intake is different?

May I recommend everybody to pick up a copy of Good Calories, Bad Calories by Gary Taubes. Very interesting.

Right. Regardless of whether high insulin levels make you fat:

1. High insulin/glucose levels are thought to result in increases in non-enzymatic glycation which is one of the mechanisms of cellular aging and

2. High insulin/glucose levels are proinflammatory which is not a good thing.

NB: the coach is talking about what diet people need or don't need to lose weight, and I'm coming at this from the optimum health view.

"May I recommend everybody to pick up a copy of Good Calories, Bad Calories by Gary Taubes. Very interesting.'

Why? This book is full of false claims.

This has been discussed extensively on numerous forums and Colpo rips it apart in They are all Mad

Go to www.anthonycolpo.com and download a free copy of the e-book which is presented on the homepage.


thanks
Coach Hale
www.maxcondition.com

I missed this the first time around Coach...does this mean you are in the gluttony and sloth camp then?

If so, what do we do with this sort of research which seems to directly support the idea that the fat loss in a carbohydrate restricted diet is primarily mediated by reductions in insulin levels?

And how do we explain the results of this study where the researchers fed the subject increasing amounts of fat over a 45 day period while keeping CHO levels at <60g/day...despite giving them nearly 5,000kcal/day (4,000 of these in the form of fat) the subjects refused to gain weight...if indeed obesity is simply a matter of excess caloric intake, shouldn't these subjects have been gaining weight at a pretty good clip rather than losing it and then leveling out? And if obesity is not insulin-mediated, why when did the researchers note that while subjects lost weight on higher caloric intake diets if those diets were low in carbohydrates, "If fat was exchanged isocalorically for glucose, the weight loss ceased."

I certainly agree that the test subjects on 0 carbohydrates lost more weight, but they definitely didn't lose more fat!

Glycogen and water loss are the reason for rapid weight loss in the first week of a ketogenic diet. If anything, they'll be losing fat at a much slower rate because they've severly impaired their metabolism. Cortisol levels are way higher and t3 levels alot lower in ketogenic diets DESPITE being the same caloric intake as regular diets.

The study continued for 45 days and yet despite enough caloric excess (in the form of liquid corn oil!) to form an additional pound and a half of fat per day, the subjects lost weight for the first two weeks and then plateaued. Seems a bit of a reach to claim this was water and glycogen loss...this is particularly hard to explain if one subscribes to the theory that obesity is a function of a positive energy balance.

Many other studies have demonstrated the efficacy of VLCKD for the sustained weight loss, even when caloric intake is not controlled and they are demonstrably more effective than fat restricted diets at promoting recomp via favorable changes in body composition by promoting fat loss over LBM (Willi 1998, Volek 2004).



Really?...do you have some evidence for this? The first study referenced in my post above indicates no significant change in cortisol or t3 levels although it did note a modest increase in t4 levels in subjects consuming a carbohydrate-restricted diet. Several other studies (Forsythe 2008, Sharmen 2004) have also noted a substantial reduction in whole-body inflammation markers with subjects on a VLCKD.

T-3 levels drop, but this may be compensated with by an increase in receptor density:

Fery R, et al. Hormonal and Metabolic Changes induced by an isocaloric isoprotienic ketogenic diet in healthy subjects. Diabete Metab (1982) 8:299 - 305.

Matzen LE and Kvetny J. The influences of caloric deprivation and food composition on TSH, thyroad hormones, and nuclear binding of T3 in mononuclear blood cells in obese women. Metabolism (1989) 38: 555-561

Lower t-3 levels are one facet of the protein-sparing effect seen during ketosis.

Cortisol is likely lower on a ketogenic diet:

Haymond MW et al. Effects of ketosis on glucose fluxin children and adults. Am J Physiol (1983) 245: E373-E378

But unfortunately also limits protein synthesis.

Correct.

Can this be compensated for with leucine intake?

Not so fast...effects appear to be controlled by caloric intake but in general, T3 levels seem to be positively correlated with ketone production.

J Endocrinol Invest. 1983 Apr;6(2):81-9
Relationships between iodothyronine peripheral metabolism and ketone bodies during hypocaloric dietary manipulations.
Pasquali R, Baraldi G, Biso P, Pasqui F, Mattioli L, Capelli M, Callivá R, Spoto M, Melchionda N, Labò G.

Relationships between iodothyronine and metabolic substrate metabolism during undernutrition were evaluated in four normal subjects who fasted for 48h (Group I) and in four groups (II to V) of obese patients who underwent selective dietary manipulations: 360 calories [carbohydrate (CHO) 40 g/day]; 800 calories containing respectively 19 g/day - ketogenic - (K) and 112 g/day - non ketogenic - (NK) of CHO; and a step-diet programme (during which total calories were progressively reduced from 2500 to 500). Serum T3 levels decreased significantly and constantly during fasting, 360 and 800 K studies, and transiently during the 800 NK diet. During the step-diet programme, a significant fall was found only when 1250 K or less were given. Conversely, serum reverse T3 rose significantly and constantly during 360 and 800 K diets, while a transient increase was found during the 800 NK diet. During the step-diet programme reverse T3 rose only when 750 calories were given. Ketogenesis developed in all studies but one (800 NK), and in the step-diet programme significantly below the 1000 calorie step. Other substrate modifications in each study were also evaluated. Serum T3 levels showed a significant correlation with ketone bodies (KB) in all the ketogenic studies, while no correlation was found in non ketogenic study (800 NK). During the step-diet programme ketone bodies and iodothyronine modifications appeared to be related to the amount of calories. Based on these results, we suggest a relationship between the dietary-induced modifications of iodothyronine metabolism and the development of ketogenesis.

This may be the reason for the increase in body temperature noted in the study above where they titrated people up to 6000kcal/day, most of it in the form of corn or olive oil...

Corn oil produced greater degrees of fat loss than olive oil:

Kasper H et al. Response of bodyweight to a low-carbohydrate, high fat diet in normal and obese subjects. Am J Clin Nutr (1973) 26: 197-204

Don't see exactly what's going on here.

If your brain uses a good 20% of your caloric intake, and can only rely on carbohydrates for ATP synthesis, how do you think people survive ketogenic diets?

Obviously your body is smarter than you and catabolizes proteins to keep you alive.

Now, how does your body go about catabolizing proteins?
Through a little process called gluconeogensis.

http://www.elmhurst.edu/~chm/vchembook/604glycogenesis.html



Now which hormone are we all familiar with that stimulates gluconeogenesis in the liver?
of course those damn glucocorticoids.

Now your probably thinking "great, but that's in the liver !"

True, gluconeogensis occurs mostly in the liver, but glucorticoids also act to mobilize amino acids from muscle tissue and other organs, which will later serve for as a substrate for gluconeogensis in the liver.



little contradicting?
remember cortisol is also a potent anti-inflammatory.

I admit I jumped the gun saying t3 would be lowered. I had forgotten that t3 increases glucagon production, which would be required during ketosis to maintain blood sugar.

Umm ... do you know how a ketogenic diet works? The brain adapts to use ketones as an energy source. Brains require 416 calories per day to function, 75% of this can be derived from ketones. Only 26 grams of glucose need to be produced once adaptation has occurred.

according to your link, fat is also a substrate for gluconeogenesis.

and at least according to the wiki, 70% of the brain's metabolism will shift from glucose to ketones. http://en.wikipedia.org/wiki/Ketone_bodies

so, muscle catabolism may happen to some extent during starvation, but not as fast as i think you're implying, and not necessarily even to maintain brain glucose.

So, we need to make 26g of CHO (see my last post). Incoming dietary protein can produce glucose at the rate of 0.58g glucose per gram of protein. Glycerol from fatty acids will be converted to glucose at a rate of 1 gram glucose per 10 grams of TAG's oxidized.

Given a meager rate of fat oxidation, say 160g/day: 16 grams of glucose produced.
Maybe the diet is not zero-carb, as very few are: 10 grams of glucose per day

Still think ketogenic diets are catabolic?

I would suggest picking up a copy of Lyle's The Ketogenic Diet.

EDIT: Proton posted while I was typing.

Don't know where you got those numbers from.

According to my sources, in a normal diet, ATP results almost entirely from glycolysis (99%+).

In starvation mode, demand for ATP becomes so great that the brain will decrease glucose utilization, but it can only do this to an extent!



After discussing this with my prof. who has a PhD in biochemistry, he assured me that under normal conditions the brain will utilize ONLY glucose for ATP synthesis. The greatest extent at which glucose utilization can decrease is 50%! Mind you that is weeks into a starvation diet of 0 calories (when glycogen stores are depleted and only proteins and lipids remain in tissue).

Both docs agree that the minimum carbohydrate intake required to stave off catabolism is 100grams (and that's for your average 160lb joe).

perhaps you didn't notice that no citation was given for that claim on wiki:

http://www.pubmedcentral.nih.gov/articlere...ubmedid=6061736

My biochem professor (PhD and department head) knows a shitload of biochem, but a relative ton of jack shit about human physiology.

You are confusing a ketogenic diet with sufficient caloric intake with a starvation diet. Provided you supply adequate calories and have the required essential fatty and amino acids (note there are no essential carbohydrates) and you have the micronutrients lined up, you can go on living and hunting walrus and whales forever on a zero carb diet and if any glucose is required, your body can happily make it from protein and fat you consume without resorting to catabolism.



As an aside, just quoting "Steven Harris, MD" or your chemistry prof (or the wiki for that matter) won't get you very far here...stick your nose in Pubmed and find some real research or primary sources to support your position...

why do you all keep bringing up ketosis... not all low carb diets are ketogenic diets. (most aren) its really easy to get out of ketosis and real damn hard to get into.

Are you changing your claims to say that low carb is not the way to go but ketogneic? so Taubes was wrong? now way... yeah I 'm a smart ass sorry.

One more thing, stop brining short terms studies they mean jack shit as many ssytems in the body regulate and manifest their effect over a longer period.

I want to see a research of weight lot, retention of results. comparing several groups with different diets.

I would disagree that its difficult to get into ketosis but the reason we are discussing them is that the argument was being made that ketogenic diets were unhealthy/catabolic/metabolically disadvantageous and its clear they are not.




Not sure how long you want. I've posted links to several six month studies (Brehm 2003, Samaha 2003, Yancy 2004) and 12 month studies (Stern 2004, Nordman 2006) and I think others but I don't know that there are any that have followed participants for more than 12 months, at least that have been published.

So a high-protein diet, without exercise, is more effective at weight loss than a conventional diet with exercise and if you add exercise to HP diet, the effects are roughly 2x the conventional diet...

Appl Physiol Nutr Metab. 2007 Aug;32(4):743-52
A randomized trial of a hypocaloric high-protein diet, with and without exercise, on weight loss, fitness, and markers of the Metabolic Syndrome in overweight and obese women.
Meckling KA, Sherfey R.

The purpose of this study was to examine the effects of 3:1 and 1:1 carbohydrate to protein ratios, hypocaloric diets with and without exercise, and risk factors associated with the Metabolic Syndrome in overweight and obese Canadian women. Groups were designated as control diet (CON), control diet with exercise (CONEx), high-protein (HP), or high-protein with exercise (HPEx). Free-living women from the Guelph community were studied in a university health and fitness facility. The participants were 44 of 60 overweight and obese women who had been randomized to the 4 weight-loss programs. Habitual diets of the subjects were energy restricted and were to contain either a 1:1 or 3:1 ratio of carbohydrate to protein energy. Subjects either exercised 3 times/week or maintained their normal level of activity for 12 weeks. The main outcome measures were weight loss, blood lipids, blood pressure, insulin, body composition, nitrogen balance, fitness, and resting energy expenditure. All groups lost weight over the 12 week period: -2.1 kg for the CON group, -4.0 kg in the CONEx group, -4.6 kg in the HP group, and -7.0 kg in the HPEx. All participants exhibited improved body composition, decreased blood pressure, and decreased waist and hip circumference. Actual diets consumed by the subjects contained ratios of carbohydrate to protein of 3.0:1, 2.7:1, 1.5:1, and 0.96:1 for the CON, CONEx, HP, and HPEx groups, respectively. Cardiovascular fitness improved in both exercise groups. There were no changes in resting energy expenditure. No adverse events were reported. Significant changes in blood lipids included decreased total cholesterol in the HP and CONEx groups, decreased low-density lipoprotein cholesterol in the HP group only, and decreased blood triglycerides in the HPEx group only. High-density lipoprotein cholesterol, fasting blood glucose, and fasting insulin levels were unaltered by diet or exercise. A high-protein diet was superior to a low-fat, high-carbohydrate diet either alone or when combined with an aerobic/resistance-training program in promoting weight loss and nitrogen balance, while similarly improving body composition and risk factors for the Metabolic Syndrome in overweight and obese Canadian women.

PMID: 17622289

"The natural question is, "What regulates fat accumulation?"

Energy balance, exercise and P-ratio

" Raise insulin levels and you accumulate fat;"

Not true under hypocaloric conditions.

"lower insulin levels and you lose fat."

In general you can expect higher fat oxidation. This does not necessarily mean you are losing bodyfat. The higher ffa oxidation can be be derived from dietary fat ingestion.

"And we secrete insulin as a response to carbohydrates in the diet"

What about amino acids that cause an increased stimulation of insulin?

thanks
Coach Hale
www.maxcondition.com




...[and] because insulin determines fat accumulation, it's quite possible that we get fat not because we eat too much or exercise too little, but because we secrete too much insulin..."-Gary Taubes

Jamie, what do you think about the varying insulin responses from amino acids vs. carbs, i.e. monophasic and biphasic, and the second phase inhibition capbilities of certain AA's?

It's ketosis a "gradient"? We all produce ketones at undetectable levels all day long. Alcohol, exercise, low carbs, lots of things can increase ketone synthesis.

All diets are ketogenic diets. Just not all bring ketones up to extra high levels. Right?


Coach Hale -- if insulin's suppression of lipolysis is so potent (as it seems to be), how would one lose fat with elevated insulin even while hypocaloric?




Second phase inhibition? I didn't know they could do that. What AAs? Where can I learn more?

ketosis is easy. all it takes is a little weightlifting to get my pee smelling like nail polish remover.

If that's the case, perhaps you can explain the earlier study I posted where they fed the subjects 6,000kcal/day, the vast majority of it in the form of fat, for over a month and yet, without exercise this huge positive energy balance resulted in....weight loss

Or the study I posted today that indicated that simply changing macro ratios in favor of protein and away from carbs, the subjects lost more weight than the high carb/low fat exercising group who were, one would presume, expending more calories?

If fat accumulation is really regulated by the degree of sloth and gluttony in our lives, how can we explain these results?

I see ASP was brought up again, but no expert can seem to give me a concrete answer about it's effectiveness and, if the studies and journals I've read were interpreted properly, the degree of the effect of ASP increases as insulin increases.

Another study that is very difficult to make sense of if you are using an energy balance model of obesity; an ad libum low carb diet causes weight loss while a calorie-restricted low fat diet actually caused weight gain...

It's interesting that we are discussing ways to spike insulin in two other threads...

It is frequently claimed that a VLCARB sets the stage for a significant loss of muscle mass as the body recruits amino acids from muscle protein to maintain blood glucose via gluconeogenesis. It is true that animals share the metabolic deficiency of the total (or almost total) inability to convert fatty acids to glucose [18]. Thus, the primary source for a substrate for gluconeogenesis is amino acid, with some help from glycerol from fat tissue triglycerides. However, when the rate of mobilization of fatty acids from fat tissue is accelerated, as, for example, during a VLCARB, the liver produces ketone bodies. The liver cannot utilize ketone bodies and thus, they flow from the liver to extra-hepatic tissues (e.g., brain, muscle) for use as a fuel. Simply stated, ketone body metabolism by the brain displaces glucose utilization and thus spares muscle mass. In other words, the brain derives energy from storage fat during a VLCARB.

Glycolytic cells and tissues (e.g., erythrocytes, renal medulla) will still need some glucose, because they do not have aerobic oxidative capacity and thus cannot use ketone bodies. However, glycolysis in these tissues leads to the release of lactate that is returned to the liver and then reconverted into glucose (the Cori cycle). Energy for this process comes from the increased oxidation of fatty acids in the liver. Thus, glycolytic tissues indirectly also run on energy derived from the fat stores.

The hormonal changes associated with a VLCARB include a reduction in the circulating levels of insulin along with increased levels of glucagon. Insulin has many actions, the most well-known of which is stimulation of glucose and amino acid uptake from the blood to various tissues. This is coupled with stimulation of anabolic processes such as protein, glycogen and fat synthesis. Glucagon has opposing effects, causing the release of glucose from glycogen and stimulation of gluconeogenesis and fat mobilization. Thus, the net stimulus would seem to be for increasing muscle protein breakdown. However, a number of studies indicate that a VLCARB results in body composition changes that favour loss of fat mass and preservation in muscle mass.

Taken from here.

Obese children.

this is a good review.
PS
The author fail to notice thr group of high performance/high intensity athletes and micronutrient choice.

further more, no long term research was done to assess immune, performance and aging effects of a VLCD ehich gives little regard to micronutrient choice.

And no one is just VLCDing. everybody eats carbs once in a while. there are issues combination of saturated fats/omega 6 and even a little carbs, the issues of going in and out of ketosis frequently.

I've shown the same effect demonstrated in adult men and women. VLCD with higher caloric intake result in more fat loss than calorie-restricted high-CHO diets.

In fact, when CHO are controlled, there appears to be almost no positive correlation between calories consumed and body weight or fat mass and even subjects consuming huge amounts of fat do not gain appreciable amounts of weight while otherwise limiting CHO intake. Which brings us right back around full circle to the Taubes hypothesis.

ASP increases triglyceride synthesis in fat-storing cells. The effects of ASP are additive and independent of those of insulin. In the studies by Van Harmelen et al., in the presence of both insulin and ASP, the combined effect was a reduction in net fatty acid output from the adipocytes, with almost complete (97%) reesterification and storage of the fatty acid available. Therefore, in combination with insulin, ASP can provide a powerful drive for fat storage. ASP also inhibits HSL (Cianflone 2002).

On the topic of insulin.

Inuslin elevation does decrease fat oxidation, but even in fasted states insulin is present. The body normally alters between the Feed/Fast cycle (anabolism and catabolism). The question is which is more prevelant at the end of the day. As i mentioned earlier even under conditions of hyperinsulinemia assuming cal defiict weight loss occurs. Insulin secretion is closely coordinated with the release of glucagon by pancreatic beta cells. In the fed state insulin increases and glucagon decreases (balancing hepatic glulcose production with the rate used by peripheral tissues)

There is a correlation between gi index and insulin prodution but this is not always the case (demonstrated with insulin index)

Some amino acids are potent stimulus' of insulin secretion (ex: leucine, and arginine)

Yes, many obese people have high insulin. But that does not mean insulin was the causative factor regarding obesity. This is a very common logical fallacy (correlation & causation effect)

thanks
Coach Hale
www.maxcondition.com

any evidence in the non-morbidly obese?

Yes. As I have posted before.

Body composition and hormonal responses to a carbohydrate-restricted diet.
Volek JS, Sharman MJ, Love DM, Avery NG, Gómez AL, Scheett TP, Kraemer WJ.
Metabolism. 2002 Jul;51(7):864-70


It should come as no surprise, however, that there are not a lot of diet studies involving normal weight individuals.

Of course I would argue that the data I have presented in this thread and elsewhere supports the opposite position. Namely that blaming obesity on gluttony and sloth is the true confusion between correlation and causation...fat people are not fat because they eat too much and exercise too little, they eat more and exercise less because they cannot access the energy they have in storage and thus are also fat.

You have yet to respond to any of my earlier queries...how do we explain weight loss in the face of thousands of 'excess' fat calories using an energy balance model of obesity? How can non-exercising individuals on a VLCD lose more weight than exercising matched controls eating a low-fat diet? If insulin is not key to fat storage, how do we explain the inability of Type I diabetics to maintain body weight without exogenous insulin under any caloric intake condition? Why do people lose more weight on ad libum low-carb diets that they do on energy restricted high-carb diets?

Yes that part is understood (ASP + insulin increase = storage city). However, I've not found a paper yet indicating if, absent of insulin, ASP is a very potent driver of fat storage. I just haven't found any evidence of such.

Not indicating this proves anything Taubes says, but I'm rather curious about it.

An oral fat load does not cause an insulin response. C3-ASP is active and traps FFA's in adipocytes. Probably not as efficient as your body would like. This is the situation in lean subjects with good insulin sensitivity.

When glucose and insulin are present, as after consumption of a mixed meal, the ASP system does not function because insulin's actions are more efficient. This is the situation in lean subjects with good insulin sensitivity.

But pity the poor fatty ... impaired glucose and fatty acid uptake means that both ASP and insulin are acting in a synergistic manner to squirrel away those calories after a meal. C3-ASP and insulin are active during fasting as well, making fat loss a rather challenging proposition.

The take-home message for the obese seems to be: reduce circulating insulin levels and make life a whole lot easier.

For the lean, the results show that fat storage does indeed occur after a pure oral fat load. (Again, C3-ASP is not as effective as insulin.) How this meshes with Benson's abstracts on mass-fat consumption and lack of weigth gain is not clear.

-------------------------------------------------------------------

The plasma C3 increment after a fat meal seems to be a physiologic process because it occurs in healthy people. This phenomenon could reflect less effective FFA trapping because of a lack of sufficient plasma glucose and insulin, which results in
stimulation of the C3-ASP system. Consequently, in insulin resistance, impaired peripheral glucose and FFA uptake could explain the higher fasting and postprandial plasma C3 concentrations observed in patients with type 2 diabetes and subjects with familial combined hyperlipidemia than in healthy, insulinsensitive subjects (19, 29, 30). Under these conditions, we cannot rule out the possibility that sources other than adipose tissue may be responsible for the postprandial C3 increment in vivo. The present study shows that in insulin-sensitive subjects, the postprandial FFA response is reduced and complement changes are prevented when glucose is added to an oral fat load. These data may explain the controversy in the literature about postprandial C3 concentrations because they depend on the type of test meal administered. We postulate that when glucose is available as a glycerol source for intracellular triacylglycerol synthesis, peripheral postprandial FFA trapping is more efficient than when glucose is not available, and the C3-ASP system is overruled.

-----------------------------------------------

Addition of glucose to an oral fat load reduces postprandial free fatty acids and prevents the postprandial increase in complement component

ABSTRACT

Background: Elevated fasting plasma concentrations of complement component 3 (C3) are associated with elevated fasting and postprandial triacylglycerol concentrations, insulin resistance, obesity, and coronary artery disease. C3 is the central component of the complement system and the precursor of acylation-stimulating protein (ASP). Insulin and ASP are principal determinants of free fatty acid (FFA) trapping by adipose tissue.

Objective: Because controversy exists concerning postprandial changes in C3 and because meal composition may influence complement activation, we studied postprandial lipemia in relation to changes in plasma C3.


Design: After an overnight fast, 6 healthy men (x_ _ SD age: 23 _2 y) underwent 4 oral liquid challenges: fat (50 g/m2 body surface), glucose (37.5 g/m2), fat and glucose (mixed test), and water (as a control test) in a random, crossover design. Results: Plasma ASP concentrations did not change postprandially in any test. Changes inC3concentration were observed only after the fat challenge: elevated concentrations occurred between 1 and 3 h, and a maximum increase of 11% occurred at 2 h (P _ 0.05). Postprandial
triacylglycerolemia did not differ significantly between the fat and mixed tests. The FFA response after the fat challenge was the highest of all the tests (P _ 0.05 for all comparisons) and was accompanied by an increase in ketone bodies (maximum at 6 h); this increase did not occur after the mixed test, which suggests less hepatic FFA delivery.

Conclusions: When glucose is added to an oral fat load, the postprandial FFA response is reduced, and the fat-specific increase in C3 is prevented. After ingestion of fat without glucose, the lack of insulin response may lead to C3-mediated peripheral FFA trapping,
which probably serves as a backup system in case of insufficient or inefficient insulin-dependent FFA trapping.

The above study has been cited numerous times (http://www.ajcn.org/cgi/citemap?id=ajcn;79/3/510) - as good a place as any to find the answer. Many of the citation have free full-text.

I cannot afford to spend any more time on this until tomorrow morning. Later 'gents.