Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels

Human and rat pineal melatonin secretion decline with aging, whereas viscer al fat and plasma insulin levels increase. Melatonin modulates fat metaboli sm 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 supplementation 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 dosage (4 mu g/ml) previously reported to attenuate the aging-a ssociated decrease in survival rate in male rats, as well as at a 10-fold l ower dosage. The higher dosage produced nocturnal plasma melatonin levels i n 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 pla sma insulin and leptin levels, were all significantly increased at middle a ge when compared to young rats. All were restored within 10 weeks to youthf ul (4 month) levels in response to both dosages of melatonin. Continued tre atment until old age maintained suppression of visceral (retroperitoneal epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) leve ls were not significantly altered by aging or melatonin treatment. Plasma t estosterone, insulin-like growth factor 1 (IGF-1) and total triiodothyronin e (T3) decreased by middle age; these aging-associated decreases were not s ignificantly altered by melatonin treatment. Thus, visceral fat, insulin an d leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since inc reased visceral fat is associated with increased insulin resistance, diabet es, and cardiovascular disease, these results suggest that appropriate mela tonin supplementation may potentially provide prophylaxis or therapy for so me prominent pathologies associated with aging.