Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat

Pineal melatonin secretion declines with aging, whereas visceral fat, plasm a insulin, and plasma leptin tend to increase. We have previously demonstra ted that daily melatonin administration at middle age suppressed male rat i ntraabdominal visceral fat, plasma leptin, and plasma insulin to youthful l evels; the current study was designed to begin investigating mechanisms tha t mediate these responses. Melatonin (0.4 mu g/ml) or vehicle was administe red in the drinking water of 10-month-old male Sprague Dawley rats (18/trea tment) for 12 weeks. Half (9/treatment) were then killed, and the other hal f were submitted to cross-over treatment for an additional 12 weeks. Twelve weeks of melatonin treatment decreased (P < 0.05) body weight (BW; by 7% r elative to controls), relative intraabdominal adiposity (by 16%), plasma le ptin (by 33%), and plasma insulin (by 25%) while increasing (P < 0.05) loco motor activity (by 19%), core body temperature (by 0.5 C), and morning plas ma corticosterone (by 154%), restoring each of these parameters toward more youthful levels. Food intake and total body fat were not changed by melato nin treatment. Melatonin-treated rats that were then crossed over to contro l treatment for a further 12 weeks gained BW, whereas control rats that wer e crossed to melatonin treatment lost BW, but food intake did not change in either group. Feed efficiency (grams of BW change per g cumulative food in take), a measure of metabolic function, was negative in melatonin-treated r ats and positive in control rats before cross-over (P < 0.001); this relati onship was reversed after cross-over (P < 0.001). Thus, melatonin treatment in middle age decreased BW, intraabdominal adiposity, plasma insulin, and plasma leptin, without altering food intake or total adiposity. These resul ts suggest that the decrease in endogenous melatonin with aging may alter m etabolism and physical activity, resulting in increased BW, visceral adipos ity, and associated detrimental metabolic consequences.