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Daily Melatonin Administration at Middle Age Suppresses Male Rate Visceral Fat, Plasma Leptin, and Plasma Insulin to Youthful Levels

Mental health Service (D.D.R) and Geriatric Research, Education and Clinical Center (C.W.W., A.M.M.), Va Puget Sound Health Care System, and Departments of Medicine (D.D.R., B.M.B., A.M.M.) and Psychiatry (D.D.R., C.W.W.) University of Washington, Seattle, Washington 98195; and Department of Physiology (S.M.Y.), Loma Linda University, Loma Linda, California, 92350

Address all correspondence and requests for reprints to: Dennis D. Rasmussen, Va Medical Center, Research Service 151, American Lake, Tacoma, Washington 98403. E-mail: drasmuss{at}u.washington.edu

Human and rat pineal melatonin secretion decline with aging, wheras visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplemntation to male Sprague Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92%) of which was consumed at night) at a dose (4 µg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as a 10-fold lower doase. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 months) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor i (IGF-I) and total triiodothyrone (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results suggest that appropriate melatonin supplementation may potentially provide prophylaxis or therapy for some prominent pathologies associated with aging.

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