So far, the evidence that supports this hypothesis is quite promising. Leptin levels in the blood do indeed increase with weight gain and decrease with weight loss. Injections of leptin in obese mutant mice cause them to reduce food intake and lose weight (and these injections work even if tiny doses are delivered directly to the hypothalamus). Injections of leptin in db mutant mice have no effect, because there are no leptin receptors in the hypothalamus for the exogenous leptin to activate.

Of those people who are morbidly obese, less than 1 percent harbor DNA mutations that disrupt the function of the leptin gene—a low rate of incidence that is not surprising, as leptin-deficient humans and mice are both in fertile, so these mutations do not pass readily to subsequent generations.

Reprinted by arrangement with Viking, a member of Penguin Group (USA) Inc., from Compass of Pleasure by David Linden. Copyright © 2011 by David J. Linden.

5 Comments

1. 1. robert schmidt 08:09 PM 7/2/11

   So how is it that humans become obese? Does this system not work well in us? Are there other overrides? Why wouldn't similar leptin treatments not work in people?

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2. 2. corriellen in reply to robert schmidt 01:10 AM 7/3/11

   Studies involving leptin supplementation in humans have been done. So far it doesn't cause long term weightloss because the subjects become less sensitive to the hormone over time.
   
   Many obese people do produce large amounts of leptin enough to make them very very thin but for some reason they have developed leptin resistance as well.
   
   Scientists have actually know about leptin's role in the body for some time now. As of now I think they are still trying to figure out ways to overcome resistance or sensitivity, which is what the scientists in this article are probably trying to pinpoint.

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3. 3. Stabby 12:41 PM 7/3/11

   There are some mechanisms that we know about and we can use to our advantage. You can produce leptin resistance with too much leptin acting on the receptors too quickly, and that seems to be what eating too much sugar, like drinking soda does. However leptin sensitivity is controlled by various cytokines and their suppressor molecules as an evolved way to maintain fat mass for a longer period of time, and when those mechanisms are induced at inappropriate times it produces leptin resistance when it's not supposed to be there. For example the adipose tissue secretes the cytokine IL-6 which travels to the hypothalamus and provokes one of its suppressor molecules SOCS-3 (and probably others, I'm not a biochemist) to downregulate leptin receptor expression, the only problem is that there are other ways to get too much IL-6 in your hypothalamus, IL-6 is also part of the inflammatory cascade, so the same chronic inflammation that is a major cause of many of the modern diseases like Alzheimers and CHD also produces leptin resistance, which makes a person fatter, and then that adipose tissue makes inflammation and the conditions caused by it worse, all in a vicious cycle.
   
   You can produce quite potent obesity in animals irrespective of calories consumed with diets high in omega-6 fatty acids or trans fats, that tends to produce an overly inflammatory situation in the cells where the suppression of the pro-inflammatory eicosanoids is too weak. It's run-away inflammation.
   
   Here is a neurosurgeon blogging about this stuff http://jackkruse.com/jacks-blog/

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4. 4. Raghuvanshi1 11:37 PM 7/5/11

   Can this theory apply to man?You don't consider the human irrationality.Every man know taking too much food is harmful to body same is true too much exercises not make you healthy.Till many people behave irrationly.Is there some tissue in brain which govern to our irrationality system?

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5. 5. sunnystrobe 01:23 PM 7/6/11

   Stabby, your entry gives an excellent explanation to the problem; it makes it all the more clear to me,again, that it's the nutritional system overload with the wrong lipids ,let's call it, 'oil slick', that's calling for trouble!
   We are the only creatures on earth to ingest denatured food; heat-damaged & condensed fat -plus- sugar concoctions were never meant to end up as 'sump oil' in our pancreas..
   I did a diet experiment with myself over the past decade or so, by eating more and more 'au naturel', with no more margarines, butter, or oil added, and cutting out biscuits & all junk foods in favour of raw and natural plant food; lost 20 kilos, and feel 20 years younger !
   
   Youthevity.com
   

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