Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats
| Autor: | Fernanda Gaspar do Amaral, Guilherme Gomes, José Cipolla-Neto, Daniella do Carmo Buonfiglio, Jéssica Andrade-Silva, José Sinésio, Lívia Clemente Motta-Teixeira, Rosana Aparecida Spadoti Dantas, Russel J. Reiter, Angela M. Ramos-Lobo, Jose Donato, Raysa Cerqueira Silva, Rafaela Parthimos, Raphael Afonso Matos |
|---|---|
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism feeding behavior melatonin Biology lcsh:Diseases of the endocrine glands. Clinical endocrinology Energy homeostasis Melatonin 03 medical and health sciences Endocrinology 0302 clinical medicine hemic and lymphatic diseases Internal medicine medicine overweight neoplasms Original Research lcsh:RC648-665 signal-transducer and activator of transcription 3 Leptin digestive oral and skin physiology brown adipose tissue thermogenesis Neuropeptide Y receptor leptin resistance Thermogenin Orexin 030104 developmental biology Hypothalamus pinealectomy Thermogenesis hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | ResearcherID Frontiers in Endocrinology Frontiers in Endocrinology, Vol 9 (2018) |
| DOI: | 10.3389/fendo.2018.00122 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|