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 )


  1. along with the previous post, this is intriguing.... do you think that a two-day "fat fast" (i.e., coconut oil in my coffee) is enough to do the job? i'm under the impression that one doesn't get the metabolic slowdown till after the third day ... not that i'd be worried about the slower calorie-burning at rest, but i do hate lower energy!

  2. Im in two-minds about the fat fast now, although it does produce astounding weight loss its probably only just adipocyte volume because fat is a strong GLP-1 stimulant. Dunno about coconut oil in the coffee, I guess if overall calorie intake is very low it shouldnt matter.

    Metabolic slowdown during fasting is a bit of a myth, especially if its only a few days, I actually few super energetic while fasting. This makes sense, catecholamines and nervous system tone should be elevated while your fasting because your body needs you to get out and about to find food :)

  3. yes, what Peter wrote about FIAF has been inspirational to me. since i'm so close to goal, just about any gimmick i can use to get results is "pie" ... figuratively speaking!

  4. I would be careful at jumping to hasty conclusions because the bulk of evidence suggests starvation and calorie deprivation long term elevates body weight if it has any effect. See crash dieters; they progressively gain weight partly because of the neuroendocrine disorders induced by starving.

    GLP-1 is given therapeutically for diabetes and those diabetic patients typically lose tons of weight because GLP-1 regulates appetite and blood glucose. they are investigating it as an anti-obesity therapy now. Obese patients and diabetic patients tend to have too little GLP-1.

    This is one of those things the CW seems to be right about: GLP-1 reduces weight, not increases it. Contrast this to insulin which invariably makes people fatter and sometimes hungrier when they begin insulin therapy.

  5. Wooo yes its a bit of a paradox, I know GLP-1 is strongly associated with weight loss and a lean phenotype, I was surprised when I found that study myself tbh. long-term starvation up-regulates AgRP/NPY in the brain which invariably promotes weight gain hence why crash dieters fail.

  6. I suppose one way of looking at it is that GLP-1 protects you from severe lipodystrophy while ketogenic dieting. Your adipocytes should be highly insulin resistant during ketogenic dieting from high rates of beta-oxidation inside them, without the anti-apoptoic protection of GLP-1 you may end up completely wasting away!

  7. I just realised Blogger ate my comment on your previous post. What I was saying is that your Scotsman anecdote sent me on a midnight PubMed crawl (pub crawl so to speak). Most of the papers are ancient and I can't get full-text but still: unlike the successful year-long starvation of the guy in Dundee, I came across reports of at least five fatalities after much shorter fasts. I read one study in particular where they starved nine women and while they lost weight, relapse rate into obesity was 50%, and the tolerance of fasting was nowhere near as good as the Scottish guy.

    I think this may be one of those things that works great in theory (autophagy! immortality! adipocyte apoptosis!) and in undamaged people like the Kitavans but not in practice for a lot of Western people who have been eating carb-laden meals every few hours all their lives. In my zeal to get to my "goal weight", I did IF for about six months on and off and let me tell you, the results have been devastating long-term. I felt GREAT initially, thought I'd found the holy grail, could forget about food essentially. Just as you describe, you feel invincible and euphoric, fuelled by catecholamines, but this wears off and what remains is a burning pile of ashes. For women at least, you're more likely to die or end up infertile, hairless and with adrenals shot to shit (or just regain all your weight eventually) if you follow extreme, unsustainable plans like this. The blogosphere is littered with examples.

    Ruper of all people had an excellent post calling Sisson out on his male-centred view of fasting. He completely ignored the fact that most studies show fasting to be ineffective or actually harmful to women. He is what he is - a marketeer. For this reason I do not read any paleo websites anymore, too many dangerous fads being pushed and I don't have the time to read the literature on every claim they make.

    I know CW is wrong about a lot of things but generally clinicians who actually treat obese patients are against people using fasting as a weight loss strategy. Reminds me of a recent Phinney podcast with JM where he seemed quite perturbed by it and he is a veteran of LC.

  8. Sidereal indeed i know that women struggle with fasting, and that men lap it up. I was hesitant to make these posts because I didnt want to be seen as promoting some kind of crash diet epidemic.

    Overall im frustrated with all the recommendations of "calorie restriction" and "calorie counting" to control weight. That is an exercise in futility because all you do is manipulate adipocyte volume, when it is adipocyte hyperplasia that is the issue in obesity.