Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high-fat-fed rats.

BACKGROUND: Melatonin is a hormone synthesized mainly by the pineal gland, and secreted only at night. Melatonin has been proposed as a modulator of glucose metabolism. METHODS: Here we studied the metabolic effects of melatonin administration alone (s.c. 10 mg/kg) or in combination with metformin (p.o. 300 mg/kg), a widely used anti-diabetic drug. These treatments were tested on glucose tolerance, insulin sensitivity and food intake in Zucker fatty rats (i.e., bearing a missense mutation in the leptin receptor gene) and high-fat fed Sprague-Dawley rats. RESULTS: Melatonin alone or in combination did not significantly modify glucose tolerance in either model. Melatonin alone in high-fat fed Sprague-Dawley improved insulin sensitivity to the level of metformin. In addition, combined treatment further ameliorated insulin sensitivity (+13%), especially during the late phase of rising glycemia. The lack of similar effects in Zucker rats suggests an involvement of leptin signaling in mediating the positive effects of melatonin. Body mass gain in Sprague-Dawley rats was decreased by both metformin, and combined metformin and melatonin. While melatonin alone did not markedly affect food intake, its combination with metformin led to a more pronounced anorexia (-17% food intake during the last week), as compared to metformin alone. CONCLUSIONS: Melatonin improves the beneficial effects of metformin on insulin sensitivity and body mass gain in high-fat fed Sprague-Dawley rats. Therefore, the combination of melatonin and metformin could be beneficial to develop dual therapies to treat or delay type 2 diabetes associated with obesity.

Food-anticipatory activity in Syrian hamsters: behavioral and molecular responses in the hypothalamus according to photoperiodic conditions.

When food availability is restricted, animals adjust their behavior according to the timing of food access. Most rodents, such as rats and mice, and a wide number of other animals express before timed food access a bout of activity, defined as food-anticipatory activity (FAA). One notable exception amongst rodents is the Syrian hamster, a photoperiodic species that is not prone to express FAA. The present study was designed to understand the reasons for the low FAA in that species. First, we used both wheel-running activity and general cage activity to assess locomotor behavior. Second, the possible effects of photoperiod was tested by challenging hamsters with restricted feeding under long (LP) or short (SP) photoperiods. Third, because daytime light may inhibit voluntary activity, hamsters were also exposed to successive steps of full and skeleton photoperiods (two 1-h light pulses simulating dawn and dusk). When hamsters were exposed to skeleton photoperiods, not full photoperiod, they expressed FAA in the wheel independently of daylength, indicating that FAA in the wheel is masked by daytime light under full photoperiods. During FAA under skeleton photoperiods, c-Fos expression was increased in the arcuate nuclei independently of the photoperiod, but differentially increased in the ventromedial and dorsomedial hypothalamic nuclei according to the photoperiod. FAA in general activity was hardly modulated by daytime light, but was reduced under SP. Together, these findings show that food-restricted Syrian hamsters are not prone to display FAA under common laboratory conditions, because of the presence of light during daytime that suppresses FAA expression in the wheel.