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Leptin Prevents Anorexics From Putting on Pounds?

Patients recovering from anorexia nervosa appear to have abnormal levels of the weight-regulating hormone leptin. The findings, reported in two pilot trials, suggest that body chemistry--in addition to mental state--impedes anorexic patients from reaching a healthy weight.

Produced in fat cells, leptin is part of a feedback loop that helps to regulate food intake and metabolism. In mice, high leptin levels suppress appetite, raise body temperature, and speed up metabolism, resulting in weight loss. Mice with abnormally low leptin levels become obese. Two research teams, one at the University of Marburg in Germany and the other at the Beth Israel Deaconess Medical Center in Boston, set out to see whether leptin plays a role in anorexia nervosa, an eating disorder in which patients essentially starve themselves.

Johannes Hebebrand and his colleagues in Marburg measured leptin levels in the blood of 13 teenage women who were undergoing treatment for anorexia. The patients, they found, had very low leptin levels at the beginning of treatment, which suggests that leptin doesn't play a role in the condition's onset. As the patients gained weight, however, the hormone shot up to above-normal levels. Although Hebebrand cautions that the results are preliminary, he says the leptin rise may leave patients vulnerable to losing weight during treatment, as high leptin levels would suppress appetite. The researchers describe their results in the current issue of Molecular Psychiatry.

The Beth Israel group measured leptin in the cerebrospinal fluid, which indicates brain levels of the hormone, of 11 patients with anorexia and 15 controls. They report in the June issue of the Journal of Clinical Endocrinology and Metabolism that the anorexic patients had normal leptin levels after treatment, even though they were still too skinny. The findings suggest, says Beth Israel endocrinologist Jeffrey Flier, that the central nervous system of recovering anorexic patients receives an erroneous signal that their weight is normal.

The studies may help explain why it is so difficult for anorexic patients to maintain a normal weight, says neuroendocrinologist Julio Licinio of the National Institute of Mental Health. "This suggests there is a biological basis for that struggle," he says. "When you put that on top of the psychological issues with anorexia, it makes it very difficult for them to gain weight."