Leptin, Ghrelin, Cortisol and Weight

We take a look at leptin, ghrelin and cortisol, three of the most talked about hormones related to weight and weight-related behaviors. There are literally hundreds of hormones and neuropeptides (e.g. chemical signals that transmit information) involved in the regulation of weight and weight related-behaviors like hunger and satiety. This article will take a look at three of the most common (leptin, ghrelin and cortisol).

Leptin
Leptin is a hormone produced in the fat cells. It plays a role in regulating body weight by signaling to the brain to reduce appetite and burn more calories. Some studies have shown that losing weight causes a marked decrease in leptin levels, which may in turn increase appetite.² More extensive research is needed, however, to confirm these findings.

Surprisingly, obesity is linked to unusually high concentrations of leptin. Some research suggests that these high, sustained concentrations make the receptor for leptin inactive and impair the very mechanism that should eliminate excess fat. ¹ In other words, although plenty of leptin is produced, it is unable to function properly. It has been theorized that medications that target leptin receptors may be helpful for weight loss, however a great deal more research is needed and must be replicated in human trials before any firm conclusions can be drawn.

Ghrelin
Ghrelin is a hormone released by the stomach that increases hunger,² slows metabolism and decreases the body's ability to burn fat. During weight loss, some studies have found that individuals who lose weight and try to keep it off make more ghrelin than they did before losing weight, as if their bodies are fighting to regain the lost fat. By contrast, those who undergo a type of bariatric surgery, where part of the stomach is removed, wind up with relatively little ghrelin which may help explain why their appetites decrease markedly after surgery.^3,4

Similar to leptin, ghrelin appears to work differently with excess weight. In a study that analyzed ghrelin concentrations, the researchers hypothesized that obese individuals would overproduce ghrelin. Unexpectedly, they were found to have less ghrelin in their blood than subjects at a normal weight. ⁵ An explanation for these findings is that excess weight may increase sensitivity to ghrelin. For example, there may be more receptors for the hormone, so not as much is needed to stimulate hunger.

Again, more research is needed before firm conclusions can be drawn about the effects of ghrelin.

Cortisol
Cortisol is a steroid hormone produced by the adrenal gland that increases as part of the body's response to stress. Some research suggests that cortisol levels may affect where body fat is stored. For example, one study found that baseline levels of cortisol had no relation to women's fat distribution. However, those women in the study whose cortisol levels jumped the most in response to stress, tended to have proportionally more abdominal fat—even if they were at a normal weight. ⁶ Other studies, however, suggest that cortisol plays a very small role or is not related at all to body fat distribution and excess weight. Additionally, no research has found that taking cortisol-suppressing supplements are beneficial for weight loss.

Bottom Line
While there is some research to suggest a connection between leptin, ghrelin, cortisol and weight, it is important to understand that the human body has a complex system of hormones that interact in a myriad of different ways. Therefore, it is not likely a simple one-to-one relationship between these hormones and weight, but rather part of a chain of physiological processes. Furthermore, there is not enough substantial evidence at this time to draw any firm conclusions.

This content is reviewed regularly. Last updated September 24, 2009.

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FOOTNOTES

¹ Wang MY, Orci L, Ravazzola M, Unger RH. Fat storage in adipocytes requires inactivation of leptin's paracrine activity: implications for treatment of human obesity. Proc Natl Acad Sci U S A. 2005 Dec13;102(50):18011-6. Epub 2005 Dec 2.

² Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001 Dec; 86(12):5992.

³ Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002 May 23; 346(21):1623-30.

⁴ Stylopoulos N, Davis P, Pettit JD, Rattner DW, Kaplan LM. Changes in serum ghrelin predict weight loss after Roux-en-Y gastric bypass in rats. Surg Endosc. 2005 Jul;19(7):942-6. Epub 2005 May 19.

⁵ Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001 Apr;50(4):707-

⁶ Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR. Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat. Psychosom Med. 2000 Sep-Oct;62(5):623-32

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