Pineal
melatonin secretion declines with aging, whereas visceral fat, plasma
insulin, and plasma
leptin tend to increase. We have previously demonstrated that daily
melatonin administration at middle age suppressed male rat intraabdominal visceral fat, plasma
leptin, and plasma
insulin to youthful levels; the current study was designed to begin investigating mechanisms that mediate these responses.
Melatonin (0.4 microg/ml) or vehicle was administered in the
drinking water of 10-month-old male Sprague Dawley rats (18/treatment) for 12 weeks. Half (9/treatment) were then killed, and the other half 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% relative to controls), relative intraabdominal adiposity (by 16%), plasma
leptin (by 33%), and plasma
insulin (by 25%) while increasing (P<0.05) locomotor activity (by 19%), core body temperature (by 0.5 C), and morning plasma
corticosterone (by 154%), restoring each of these parameters toward more youthful levels. Food intake and total body fat were not changed by
melatonin treatment.
Melatonin-treated rats that were then crossed over to control treatment for a further 12 weeks gained BW, whereas control rats that were 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 intake), a measure of metabolic function, was negative in
melatonin-treated rats and positive in control rats before cross-over (P<0.001); this relationship 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 results suggest that the decrease in endogenous
melatonin with aging may alter metabolism and physical activity, resulting in increased BW, visceral adiposity, and associated detrimental metabolic consequences.