Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats

作者：Buonfiglio Daniella; Parthimos Rafaela; Dantas Rosana; Silva Raysa Cerqueira; Gomes Guilherme; Andrade Silva Jessica; Ramos Lobo Angela; Amaral Fernanda Gaspar; Matos Raphael; Sinesio Jose Jr; Motta Teixeira Livia Clemente; Donato Jose Jr; Reiter Russel J; Cipolla Neto Jose^*

来源：Frontiers in Endocrinology, 2018, 9: 122.

DOI：10.3389/fendo.2018.00122

• melatonin
• feeding behavior
• pinealectomy
• leptin resistance
• signal-transducer and activator of transcription 3
• brown adipose tissue
• thermogenesis
• overweight

Melatonin (Mel), a molecule that conveys photoperiodic information to the organisms, is also involved in the regulation of energy homeostasis. Mechanisms of action of Mel in the energy balance remain unclear; herein we investigated how Mel regulates energy intake and expenditure to promote a proper energy balance. Male Wistar rats were assigned to control, control + Mel, pinealectomized (PINX) and PINX + Mel groups. To restore a 24-h rhythm, Mel (1 mg/kg) was added to the drinking water exclusively during the dark phase for 13 weeks. After this treatment period, rats were subjected to a 24-h fasting test, an acute leptin responsiveness test and cold challenge. Mel treatment reduced food intake, body weight, and adiposity. When challenged to 24-h fasting, Mel-treated rats also showed reduced hyperphagia when the food was replaced. Remarkably, PINX rats exhibited leptin resistance; this was likely related to the capacity of leptin to affect body weight, food intake, and hypothalamic signal-transducer and activator of transcription 3 phosphorylation, all of which were reduced. Mel treatment restored leptin sensitivity in PINX rats. An increased hypothalamic expression of agouti-related peptide (Agrp), neuropeptide Y, and Orexin was observed in the PINX group while Mel treatment reduced the expression of Agrp and Orexin. In addition, PINX rats presented lower UCP1 protein levels in the brown adipose tissue and required higher tail vasoconstriction to get a proper thermogenic response to cold challenge. Our findings reveal a previously unrecognized interaction of Mel and leptin in the hypothalamus to regulate the energy balance. These findings may help to explain the high incidence of metabolic diseases in individuals exposed to light at night.

• 出版日期2018-3-27