Our "Frenemy" Leptin


When I talk to fellow nonscientists about my job here at SiS, I find that many folks are most interested in topics that span the murky divide between things like nature and nurture, the conscious and unconscious, what we can control and what we cannot. Basically, which parts of us are governed by things like active decision-making and willpower, and what is simply controlled by our biology.

To get even murkier, that distinction is not cut and dried. Most things are controlled by...both. One of the best examples of this is weight loss. At first glance, it really should just be simple math - control your intake, burn more calories than you consume on a daily basis, and you will lose weight. At the very root of the issue, this is true.

But there are complicating biological factors, as covered by NPR's Morning Edition today. Even though our active minds might be telling our body one thing, hormones could be telling it something different. One of these hormones, called leptin, is produced by fat cells. When you start dieting and begin depleting your fat reserves, leptin levels drop. This tells your brain to brace itself for starvation. While our conscious brain knows this isn't true - we're not starving at all, just trying to become more healthy - our biology overrides and slows down our metabolism, which makes losing weight even more difficult. Then, to kick us while we're down, the brain sends a signal to stimulate the appetite. So, while one part of our brain is sending you to bed without dessert, the other is sending you screaming to McDonald's. Thanks, biology.

The researcher interviewed for the piece, Donna Ryan of the Pennington Biomedical Research Center in Baton Rouge, said that this biological disconnect amounts to what she calls a "caloric handicap" for people who diet. Essentially, if someone loses 50 pounds to hit a goal of 150, that person can't eat the same amount of calories in a day to maintain that weight as a friend who has always weighed around 150. So it's not about hitting a target once and then resuming past behaviors; it's about adopting a lifelong strategy of healthy eating and exercising. This, of course, requires a lot of willpower.

If you'd like to learn more about our frenemy leptin, check out this video from the Center for Genetic Medicine's Silverstein Lecture Series. It features Jeffrey Friedman, a professor at The Rockefeller University who first discovered the hormone.




Listen, it is believed that leptin acts as a lipostato: when the amount of fat stored in adipocytes rises, leptin is released into the bloodstream, which is a signal (negative feedback) that informs the hypothalamus that the body has enough reserves and should suppress the appetite. With increasing mass of adipose tissue beyond the point of balance, increases the synthesis and secretion of leptin are stimulated so many offsetting effects in the hypothalamus: decreased appetite by stimulating anorexigenic peptides (which cause loss of appetite) and suppressing the production of orexigenic peptides (from the Greek orexis means appetite), increased energy expenditure by increasing the basal metabolic rate and body temperature changes in addition to the hormonal equilibrium point to decrease lipogenesis (fat production) and increase lipolysis (use stored fat for energy) in adipose tissue. The regulation of leptin secretion is a long-term, primarily due to changes in the level of body mass and stimulating effects of insulin. However, many obese people have high serum concentrations of leptin or leptin resistance, suggesting that other molecules such as ghrelin, serotonin, cholecystokinin and neuropeptide Y also have an effect on satiety and contribute to the regulation of body weight.
Michael Feder

As I have understood Leptin is a hormone produced and mostly by adipocytes (fat cells) that also occur in the hypothalamus in the placenta and ovaries. I can not understand that there is so much misinformation about this issue as it was discovered in 1994. I wish someone would answer me because it is so common in young people lately ...

Certain foods can sent a signal to the brain that the body is full. From my own experience I would include : low fat greek yougurt, low fat cottage cheese, and sugar free fudgsicles. I also think that lasting weight-loss is not a function of willpower but is acheived by using one's imagination

from what i have heard: this does not work in humans, because humans are not lacking leptin. these "ob mice" are modified to lack leptin. obese humans are insensitive to leptin not lacking. adding leptin would most likely worsen the insensitivity, long term. much like with insulin: injecting insulin is the least ideal treatment for the insensitive.

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