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.


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?















12 comments:

  1. This is truefact.

    I developed a similar hypothesis myself 5 years ago, and had the opportunity to test it. If all of the horrible symptoms I have after losing weight are the result of excessive adipocyte numbers making insufficient leptin, then HYPOTHETICALLY the following would be true:

    1) My basal leptin will be severely deficient in spite of adequate body fat in KGs
    2) Leptin replacement will correct all symptoms I associate with weight loss.

    These were proven beyond shadow of doubt, as my basal leptin was in the range of an anoretic, and leptin therapy totally reversed symptoms.

    Why do stalls happen?
    Why are low carb diets not sufficient to correct obesity?

    Because obesity is a permanent disorder, which cannot be energy deprived away. The adipocytes are abnormal, the fat tissue is damaged via adipocyte hyperplasia.

    Please note, though I no longer take leptin therapy (NOOOO) it is much much much easier for me to maintain my weight at this size (120~ pounds) than it was before. I believe the reconstructive surgeries I have had removed a great deal of my excessive adipocytes, and leptin therapy may have helped with adipocyte apoptosis.


    Either way, yes... this explains why people don't get skinny on atkins,
    why they gain weight after losing lots of weight even in ketosis,
    Why people start to feel terrible after awhile of dieting and body fat atrophy.

    First hand personal experience: Leptin therapy stops ALL of this.

    Unfortunately no one gives a shit because leptin therapy is not marketable.

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  2. Leptin resistance is a made up boogey man, which I've advocated for in the past as well.

    High leptin levels do not imply resistance.

    If these people had a medical education even basically they would observe a great many pathophysiologies where something might be elevated but it doesn't mean the body "resists" it... all it means is the marker is elevated as a symptom/result of the pathology.

    High BNP in heart failure doesn't mean patients in heart failure resist the actions of BNP (diuresis). All it means is a primary defect in the heart muscle conductivity or function results in congestion and thus compensatory BNP release. The BNP doesn't work because the heart failure is not related to BNP.

    Obesity and leptin is exactly the same thing.

    Too bad obesity researchers are allergic to observing human patients, knowing anything about medicine, seeing the big picture, thinking abstractly, thinking evens lightly non-linearly, or having basic common frigging sense.

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  3. Great post. Once again my comment disappeared; luckily I'm not on the paranoid spectrum of things.

    This is basically what the so-called setpoint is and that first graph explains pretty much everything about obesity and its treatment resistance. As usual, the key issue is what's going on in the adipocyte/periphery, not the brain. Obesity is an illness of fat tissue dysregulation. This is why no existing therapy really works and when the odd outlier manages to forcefully starve the fat cells down, relapse is pretty close to 100%.

    The only thing I would dispute in Woo's comment is that they don't give a shit. I was reading a recent-ish review paper the other day from mainstream important people and was SHOCKED to find the same stuff about leptin discussed as in the blogosphere. Look:

    http://www.ncbi.nlm.nih.gov/pubmed/20935667

    They even have a neat table showing the reversal of all the horrible metabolic adaptation sx following weight loss with leptin treatment. THEY GET IT.

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  4. Aslong as theres financial profit to be made, someone will find a way. That much you can count on. So I expect at some point leptin supplements to be available, I dont think exogenous leptin is practical because it needs to be injected but rather drugs that stimulate leptin secretion will likely come on the market.

    The problem so far is that they dont seem to know exactly the molecular pathways that cause leptin secretion, the paper I found on the carb->fat pathway is vague at best and likely only half the story as im sure theres other things causing leptin secretion.

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  5. Leptin is primarily released from adipocytes particularly when acted upon by insulin.

    In studies they typically use decline of leptin as a marker for dietary therapy success. Subjects who have the sharpest declines of leptin always lose more body fat / improve met syn because leptin follows insulin follows metabolic FUBARy.

    Fatties have very high leptin because they are hyperinsulinemic, leptin levels can be slashed pretty rapidly just by fasting to reduce insulin levels.

    Obviously low carb diets are the most effective ones for reducing leptin. THey are also similarly effective for reducing insulin thus body fat.

    I agree they will probably try to make up a drug to mimic leptin. Id on't know about you but I won't touch that crap with a ten foot pole. If leptin drugs will be anything like oral insulinogenic (OHA) drugs, it's safe to say the pills will barely work with tons of side effects meanwhile plain old injected insulin is relatively much more effective and w/o long term risks.

    Of course no one makes money from insulin, just like no one can make money from leptin.

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  6. I agree; the pills will be horrible but fat women will still eat them like candy despite the risks because there is almost nothing worse in our society than being fat.

    Whoever comes up with a pill that causes adipocyte apoptosis will be rich, even if the pill happens to also waste heart tissue and brain cells.

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  7. I was reading over the stuff I posted on before about adipose tissue vasculature and killing fat cells by inhibiting angiogenesis. I sometimes wonder if obesity is like a "cancer" of the adipose tissue. They already have drugs that can kill adipocytes. Its quite clear that fat tissue growth drives higher calorie intake as I posted on before, as the drugs that kill the adipocytes result in decreased food intake in the animals.

    http://www.ncbi.nlm.nih.gov/pubmed/22225867
    http://www.ncbi.nlm.nih.gov/pubmed/20103704

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  8. Have there been human trials yet?

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  9. Dunno Sidereal, although there is studies done on monkeys so I suppose quite close to humans....blogged about it here....

    http://kindkehealthnotes.blogspot.co.uk/2012/05/fat-tissue-growth-drives-over-eating.html

    I am utterly convinced that fat tissue growth ( angiogensis/adipocyte hyperplasia ) is the issue with obesity and in particular why obesity and cancer are so strongly associated. Whatever environmental factor is making is susceptible to obesity is also making us susceptible to cancer.

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  10. fructose and omega 6s, plus all those healthywholegrains, i'm convinced!

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  11. This is an excellent post! I really understand how fat tissue works. The comments are helpful as well.

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