Depressed patients might one day be asked: Have you had your leptin today?

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Having leptin each day may keep depression away.

Leptin, a hormone produced in fat tissue, regulates our appetite and weight, but it may do a whole lot more. New research in animals at the Health Science Center suggests that low levels of leptin may be correlated with depression-like features, and that leptin possesses antidepressant-like properties.

The findings are in the Jan. 16 online edition of the Proceedings of the National Academy of Sciences.

“We are trying to determine the interplay between circulating metabolic hormones, feeding behavior and emotionality,” said senior author Xin-Yun Lu, M.D., Ph.D., assistant professor of pharmacology at the Health Science Center. “In our study, we used chronic stress, which is a trigger of depression and eating disorders.”

The study was performed in rats. After exposure to chronic unpredictable stress for two weeks, rats drank less of a sweet solution (sucrose). This behavior has been viewed as anhedonia, or lack of pleasure seeking, a sign of depression. The rats also were less likely to explore a new environment, and they showed depression-like behavior in the most widely used animal test for antidepressants. The analysis of hormone levels revealed that blood plasma levels of leptin were low in the stressed animals.

“The ability of leptin to get into the brain, and to bind to leptin receptors in parts of the brain thought to be important in depression, led us to begin to investigate the role of leptin in depression-like behavior,” Dr. Lu said.

Leptin reversed the behavioral deficits of the chronically stressed animals. The research group also found that leptin had antidepressant activity, comparable to that seen with standard antidepressants, in non-stressed animals in a test often used to detect potential antidepressants. These effects seemed to be due to activity of leptin in an area of the brain (the hippocampus) that is separate from another area thought to be responsible for its effects on energy metabolism (the hypothalamus). “This interesting research marks leptin for future study as a potential new type of antidepressant,” said Alan Frazer, Ph.D., professor and chairman of pharmacology at the Health Science Center and a collaborator on the study.

The research team now hopes to explain the neural mechanisms by which leptin modulates depression-like behaviors, and whether leptin interacts with the therapeutic targets of classical antidepressants.

While the researchers emphasize that they do not know whether leptin levels decline when people are chronically stressed or whether leptin will work the same way in depressed people, they speculate that depressed patients with low leptin levels might have a better chance to respond to leptin treatment.

In addition to Drs. Lu and Frazer, study authors from the Health Science Center department of pharmacology include Chung Sub Kim, senior research assistant, and Wei Zhang, M.D., Ph.D., assistant professor.



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