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

Autor(es):Mostrar menos -

Buonfiglio, Daniella ^[1] ; Parthimos, Rafaela ^[1] ; Dantas, Rosana ^[1] ; Silva, Raysa Cerqueira ^[1] ; Gomes, Guilherme ^[2] ; Andrade-Silva, Jessica ^[1] ; Ramos-Lobo, Angela ^[1] ; Amaral, Fernanda Gaspar ^[3] ; Matos, Raphael ^[1] ; Sinesio, Jr., Jose ^[1] ; Motta-Teixeira, Livia Clemente ^[1] ; Donato, Jr., Jose ^[1] ; Reiter, Russel J. ^[4] ; Cipolla-Neto, Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci 1, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sao Carlos Inst Phys IFSC, Dept Phys & Interdisciplinary Sci FCI, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Physiol, Sao Paulo - Brazil

^[4] UT Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX - USA

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 9, MAR 27 2018.
• Citações Web of Science: 13

Resumo

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. (AU)

• Processo FAPESP: 15/26190-6 - O papel central da melatonina no controle alimentar e metabolismo energético: interação da melatonina e leptina
• Beneficiário: Daniella Do Carmo Buonfiglio
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/24956-4 - Efeitos da ausência da melatonina na lactação e no comportamento maternal
• Beneficiário: Rafaela Panaiotta Parthimos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/01882-8 - O papel dos receptores de melatonina no consumo alimentar, balanço energético e na via de sinalização da leptina
• Beneficiário: Daniella Do Carmo Buonfiglio
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/50457-0 - Melatonina e a regulação do metabolismo energético: estudos básicos, clínicos e epidemiológicos
• Beneficiário: José Cipolla Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático