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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 9, MAR 27 2018.
• Web of Science Citations: 13

Abstract

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)

• FAPESP's process: 15/26190-6 - Melatonin central role in food control and energy metabolism: interaction of melatonin and leptin
• Grantee: Daniella Do Carmo Buonfiglio
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/24956-4 - Effects of melatonin absence on lactation and maternal behavior
• Grantee: Rafaela Panaiotta Parthimos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/01882-8 - The central role of melatonin receptors on food intake, energy balance and leptin pathway
• Grantee: Daniella Do Carmo Buonfiglio
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 14/50457-0 - Melatonin and the control of energy metabolism: basic, clinical and epidemiological research
• Grantee: José Cipolla Neto
• Support Opportunities: Research Projects - Thematic Grants