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Why Losing Weight is Unnatural or the “Holy Grail” of Weight-Loss Maintenance

I am currently at the 27th Annual Scientific Meeting of The Obesity Society (TOS) here in Washington DC.

Among the many excellent presentations, the one that I found of particular interest, was a keynote talk on the weight-reduced state by Rudulph Leibel, Columbia University, New York). This presentation addressed the important issue of why weight loss is so difficult to maintain and relapse (or weight regain) is the rule rather than the exception.

As Leibel and colleagues demonstrated in a now classic paper published in the New England Journal of Medicine back in 1995, even a 5 or 10% weight loss can lead to a rapid and sometimes drastic reduction in total energy expenditure, thereby very quickly canceling out the energy deficit created by caloric restriction.

The clinical expression of this reduction in energy expenditure is of course the infamous weight-loss plateau, which ultimately limits the magnitude of virtually every weight-loss attempt.

In his talk Leibel attributed this weight-loss-associated fall in energy expenditure to an “asymmetric” physiological response to leptin. Thus, although leptin appears to have little effect on the homeostatic system across a wide range of levels, when leptin levels drop below a putative “threshold” (as in weight loss), it triggers a powerful anabolic response resulting in a reduction in energy expenditure and an increase in orexegenic signals.

In his presentation, Leibel described how administration of low-dose leptin, just enough to raise leptin back to the levels that existed prior to weight loss, can prevent this anabolic and orexogenic response.

Functional MRI studies now show that leptin administration after weight loss also reduces activation of the hypothalamus and limbic systems, thus restoring the function of both the homeostatic and hedonic systems to the preweight-loss state.

There is some evidence to suggest that obese individuals may have higher “leptin” thresholds making them more sensitive to weight loss and perhaps more efficient in defending their body weight. It appears that once a higher bodyweight is maintained this threshold is changed to a higher level, perhaps because higher leptin levels result in structural changes in hypothalamic excitory synapses.

Once this higher threshold is established, any attempt at weight loss essentially moves the patient into a “non-physiological” hypometabolic state which not only reduces energy expenditure but also activates counter-regulatory “anabolic” behaviour. This makes it so difficult, if not impossible, for patients to maintain weight-loss in the long-term without continued caloric restriction and considerable amounts of exercise.

Clearly, the ability to restore the anabolic physiological metabolic state following weight loss back to a eumetabolic state at a lower body weight would be the “Holy Grail” of weight loss maintenance.

Whether or not administration of leptin (or a leptin analogue) can ultimately provide a safe and effective solution to this conundrum remains to be seen.

Washington DC


  1. So, gaining weight means a higher leptin threshold, and then loosing weight below that threshold puts a person into a “non-physiological hypometabolic state which not only reduces energy expenditure but also activates counter regulatory anabolic behavior.”

    The popular notion is that being overweight is like having a broken bone:
    You go through treatment (you diet and exercise, or you wear a cast) and then you’re healed. You’re back to normal, and as long as you don’t do something really stupid (like binge on donuts, or ski diamonds when you’re a novice) you’ll be fine.

    In fact, to gain weight is to permanently damage your metabolism.

    People think that after they loose the weight they’ll be healed and healthy.

    No wonder people regain weight they’ve lost. They think they’re now ok, so they can eat like everybody else, and be fine as long as they don’t overdo the donuts. They don’t know they’re in a hypometabolic state.

    People in the National Weight Control Registry who loose weight and keep it off, eat fewer calories than most people just to stay the same weight. It seems to me they have to eat a diet that compensates for their damaged metabolism, like a diabetic has to be picky about sugar intake, or someone with kidney disease limits potassium, or a celiac avoids wheat. The fat is gone, but the altered metabolism still needs a special diet.

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  2. Leptin manipulation has often been the subject of discussion among bodybuilding populations as well. In fact, many leading nutrition coaches for competitive bodybuilders attempt to stave off reductions in leptin with periodic “refeeds”. Since some have demonstrated that significant carbohydrate ingestion can increase leptin levels these periods of higher carbohydrate intake are used to prevent metabolic changes that lead to a weight loss plateau.

    Whether this actually works is subject to debate as there are many factors that influence fat loss in this population, but there is no doubt that having scheduled higher calorie intakes consisting of higher glycemic foods provides a psychological break from “dieting”.

    If this method does work, perhaps it could serve as a viable option to prevent the slowing of the metabolism in obese people when on a calorically restrictive program.

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  3. That’s very interesting.

    Bodybuilders, and other athletes, show the amazing range of possibility for a human body. For these people, changing body composition and skills is the norm. We who try to go from obese to ordinary, can take inspiration from people who put in the hard work to go from ordinary to exceptional.

    I wonder if “refeeds”, perhaps by another name, are used by those devising diets to treat obesity.

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  4. I really like your writing style, superb information, regards for putting up : D.

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