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The Lowdown on Leptin

Why this natural hormone may someday unlock the key to weight control.

Researchers once thought that body fat was as sedentary as the people who accumulated it. Through animal studies, scientists subsequently learned that adipose tissue is quite active in the way our bodies balance energy and control weight (Harris 2000). Further investigation ultimately led to the discovery of leptin, a hormone that is produced by and resides in adipose tissue (Baile, Della-Fera & Martin 2000). In the decade or so since leptin was identified, more and more studies have focused on how this hormone affects energy balance, obesity and multiple body systems. Here’s what researchers have uncovered.

The Leptin Loop

The human body works diligently to maintain an energy balance, known as homeostasis. One player in this balancing effort is the naturally occurring hormone leptin (a term derived from the Greek root leptos, meaning thin). Leptin acts as a messenger to the hypothalamus (a part of the brain also known as the satiety center), letting it know how much energy is stored in the body at any given time. This constant tracking regulates energy intake and expenditure, helping to maintain a steady body weight (Jéquier 2002).

It appears that, in response to this regulatory loop, leptin levels decrease when body weight drops and increase when body weight rises. As leptin levels go up, leptin receptors signal the hypothalamus to stop eating and increase energy expenditure. Essentially, the brain hears this message: The body’s energy stores are adequate, and there is no need to eat to increase them.

How much leptin is expressed in the body is affected by how much adipose tissue is present; greater body fat is correlated with increased synthesis and secretion of leptin in both rodent and human subjects (Ahima & Flier 2000).

Of Mice and Men

Studies involving mice have advanced the theory of how leptin works. When leptin was administered to obese mice that lacked the hormone because of a genetic mutation, the mice did, in fact, lose weight (Jéquier 2002). Unfortunately, the way leptin acts in humans is far less straightforward.

Leptin levels are influenced not only by body fat but also by how much an individual consumes. For example, after fasting, leptin levels decrease within hours in both humans and rodents. However, whereas leptin levels increase in mice soon after they consume food, levels do not change immediately after human subjects eat (Ahima & Flier 2000). This difference between mice and men suggests that leptin is not involved in satiation (the suppression of hunger by eating) or satiety (the absence of hunger) in humans (Jéquier 2002).

Independent of when rodents or humans consume food, leptin levels appear to fluctuate throughout the course of the day. Concentrations tend to be lower at noon and then increase after 3:00 pm (Jéquier 2002). Leptin is typically expressed at a higher degree at night in both humans and rodents (Baile, Della-Fera & Martin 2000).

Fat Chat

If greater stores of adipose tissue signal greater secretion of leptin, it would stand to reason that increased leptin levels would assist in weight loss, right? Again, researchers examined our furry rodent friends to test this hypothesis. When given leptin, rats ate less and expended more energy (Ahima & Flier 2000). In fact, in addition to promoting weight loss, leptin destroyed fat cells in the rodents, but lean body mass was spared, which typically does not happen during starvation.

Needless to say, these promising results led to high hopes among scientists that leptin might be the “antiobesity hormone.” Unfortunately, this bubble burst when subsequent human studies did not yield the same results. When leptin was administered to obese people, it did not lead to weight reduction or obesity prevention (Ahima & Flier 2000). And while further human studies confirmed that leptin concentrations are higher in obese people, subjects given extra leptin did not eat less or expend more energy as expected (Jéquier 2002).

These disappointing results led to the next chapter in the leptin investigation, in which scientists turned their focus to leptin resistance, which occurs when the body fails to respond to increased levels of the hormone.

Preliminary investigations involving rats suggest that leptin resistance may occur because of defects in the leptin receptors and transporters. Obese rats given leptin via the bloodstream failed to respond with weight loss (Jéquier 2002). However, when the hormone was administered directly to the brain, the rats did lose weight. This finding has led scientists to believe that obese humans may have a defect in the way their bodies signal the leptin receptors and transport leptin through the bloodstream to the brain.

To further confuse matters, some obese human beings appear to have low levels of leptin despite having high levels of body fat (Ahima & Flier 2000). It has not been determined whether these people have a defect in the way their bodies synthesize or secrete the hormone. However, it has been theorized that low levels of leptin may contribute to weight gain by enhancing appetite and increasing energy efficiency.

Although the jury is still out on how leptin works, it is no longer considered the antiobesity hormone. It is now thought that the body originally produced leptin to help avert starvation during times when food was scarce but now uses the hormone differently when food is readily available (Jéquier 2002).

Leptin and Food Intake

What do all these findings on leptin have to do with your clients who are trying to lose weight? Well, if leptin levels drop when food scarcity restricts intake, won’t something similar happen when clients are dieting? My educated guess is yes. It just may turn out that the kind of self-imposed starvation we call “dieting” prompts the body to fight a perceived “famine” by eating more! If this proves to be true, it is one more reason why people who severely restrict their caloric intake may be fighting a losing battle.

But what about clients who don’t restrict their caloric intake? Studies have shown that chronic high-fat diets can also contribute to leptin resistance if individuals don’t increase their energy expenditure (Heshka & Jones 2000). If it turns out that dietary fat adversely affects the way the leptin receptors function, clients will have one more reason to maintain a lower-fat diet (Heshka & Jones 2000).

Leptin and Exercise

There is also a growing body of research to consider on leptin and exercise in both mice and men. Studies on rodents have found that acute bouts of exercise lead to decreases in plasma leptin levels (Houmard et al. 2000). While some human research involving obese males has shown that endurance exercise training can decrease leptin levels (Pasman, Westerterp-Plantenga & Saris 1998), other research has not reached the same conclusion (Houmard et al. 2000).

Researchers have found a link between leptin and insulin resistance, which can lead to obesity and type 2 diabetes. A preliminary investigation suggested that increased leptin levels may negatively affect insulin resistance (Harris 2000). However, a later study found that insulin action could improve in people who participated in a 7-day training program without any associated change in leptin levels (Houmard et al. 2000). Still another study found that subjects who completed an intensive 3-week exercise course showed significantly reduced leptin levels, which correlated with lower insulin levels (Gomez-Merino et al. 2000). This led the researchers to suggest that leptin and insulin may work together to control energy balance; it also led to the belief that leptin may assist in the recovery from prolonged, exhaustive exercise by helping to restore body fuel (Gomez-Merino et al. 2002). ‰

Like studies on leptin and diet, research on exercise and leptin remains inconclusive. For example, no one has been able to quantify how much or how long you would need to exercise to affect leptin behavior. It is also unknown why exercise appears to affect leptin levels in men and women in significantly different ways (see “Ladies and Leptin” on page 32). However, research has shown that long-term changes in diet and exercise can decrease leptin levels and improve the cardiovascular disease risk profile (blood pressure and lipid concentrations) in sedentary people (Reseland et al. 2001).

The Leptin Leap

Much research needs to be done before we can really understand how leptin contributes to weight gain in humans. Until that time, remind your clients that exercise helps us lose body fat, in addition to providing other health benefits. In the final analysis, it just may turn out that an active lifestyle and a sound diet assist in normalizing leptin action and help us achieve our desired energy balance.

Ladies and Leptin

Low and behold, leptin is one more arena in which men and women differ. For example, studies have shown that leptin levels are higher in women than in men—regardless of percent body fat (Harris 2000). Since leptin appears to be active in maintaining energy balance, the higher levels may help explain why women tend to maintain a greater percentage of body fat than men.

Studies have also shown that leptin is essential for female reproduction. Although found mostly in adipose tissue, the hormone is also found in the female reproductive organs and plays a role in the release of reproductive hormones. In addition, leptin appears to correlate to the ebb and flow of estrogen during a woman’s menstrual cycle (Harris 2000).

When it comes to exercise, leptin studies have also uncovered gender differences. Researchers examined whether exercise training would alter the relationship between leptin and body fat differently in male and female subjects (Hickey et al. 1997). The study involved sedentary middle-aged men and women with similar aerobic capacities, although the females had significantly lower body fat than the men at the start of the study. After 12 weeks of aerobic exercise training, the investigators evaluated and compared leptin concentrations. Levels had not changed in the men, but had decreased by 17.5 percent in the women, even after the researchers allowed for the female subjects’ lower body fat. Neither group experienced changes in body composition (Hickey et al. 1997). However, another study that compared leptin levels in men and women found no gender differences after short-term exercise training (Houmard et al. 2000).

Although more studies are needed in this area, these preliminary findings may begin to explain why women and men respond differently to diet and exercise. Because leptin is linked to fertility, the female body may actually lower its levels of this hormone—thereby stimulating food intake—in order to protect reproductive function. If this is so, losing weight could be that much harder for women than for men, despite any willpower or desire to shed pounds.

Until more is known about leptin, the message to convey to your female clients is this: The reason real women have real curves is to ensure the continuation of our species!


Ahima, R.S., & Flier, J.S. 2000. Leptin. Annual Review of Physiology, 62, 413-37.
Baile, C.A., Della-Fera, M.A., & Martin, R.J. 2000. Regulation of metabolism and body fat mass by leptin. Annual Review of Physiology, 20, 105-27.
Gomez-Merino, D., et al. 2002. Decrease in serum leptin after prolonged physical activity in men. Medicine & Science in Sports & Exercise, 34 (10), 1594-9.
Harris, R.B.S. 2000. Leptin—much more than a satiety signal. Annual Review of Nutrition, 20, 45-75.
Heshka, J.T., & Jones, P.J.H. 2000. A role for dietary fat in leptin receptor, OB-Rb, function. Life Sciences, 69, 987-1003.
Hickey, M.S., et al. 1997. Gender-dependent effects of exercise training on serum leptin levels in humans. American Journal of Physiology, Endocrinology & Metabolism, 272 (35), E562-6.
Houmard, J.A., et al. 2000. Effect of short-term exercise training on leptin and insulin action. Metabolism, 49 (7), 858-61.
Jéquier, E. 2002. Leptin signaling, adiposity and energy balance. Annals of New York Academy of Sciences, 967, 379-88.
Pasman, W.J., Westerterp-Plantenga, M.S., & Saris, W.H.M. 1998. The effect of exercise training on leptin levels in obese males. American Journal of Physiology, Endocrinology and Metabolism, 274 (37), E280-6.
Reseland, J.E., et al. 2001. Effect of long-term changes in diet and exercise on plasma leptin concentrations. American Journal of Clinical Nutrition, 72, 240-5.


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Jenna A. Bell, PhD, RD

Jenna A. Bell, PhD, RD, holds a doctorate degree in exercise science and a master's degree in nutrition. She is a popular speaker and writer for IDEA Fitness Journal.

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