Removing melatonin receptor type 1 signaling leads to selective leptin resistance in the arcuate nucleus

Autor(es)

Buonfiglio, Daniella ^{[1, 2, 3]} ; Tchio, Cynthia ^{[2, 3]} ; Furigo, Isadora ^[1] ; Donato, Jr., Jose ^[1] ; Baba, Kenkichi ^{[2, 3]} ; Cipolla-Neto, Jose ^[1] ; Tosini, Gianluca ^{[2, 3]}

Afiliação do(s) autor(es)

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

^[2] Morehouse Sch Med, Dept Pharmacol & Toxicol, Atlanta, GA 30310 - USA

^[3] Morehouse Sch Med, Neurosci Inst, Atlanta, GA 30310 - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pineal Research; v. 67, n. 2 SEP 2019.
• Citações Web of Science: 2

Resumo

Recent studies have highlighted the involvement of melatonin in the regulation of energy homeostasis. In this study, we report that mice lacking melatonin receptor 1 (MT1KO) gained more weight, had a higher cumulative food intake, and were more hyperphagic after fasting compared to controls (WT). In response to a leptin injection, MT1KO mice showed a diminished reduction in body weight and food intake. To evaluate hypothalamic leptin signaling, we tested leptin-induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3). Leptin failed to induce STAT3 phosphorylation in MT1KO mice beyond levels observed in mice injected with phosphate-buffered saline (PBS). Furthermore, STAT3 phosphorylation within the arcuate nucleus (ARH) was decreased in MT1KO mice. Leptin receptor mRNA levels in the hypothalamus of MT1KO were significantly reduced (about 50%) compared to WT. This study shows that: (a) MT1 deficiency causes weight gain and increased food intake; (b) a lack of MT1 signaling induces leptin resistance; (c) leptin resistance is ARH region-specific; and (d) leptin resistance is likely due to down-regulation of the leptin receptor. Our data demonstrate that MT1 signaling is an important modulator of leptin signaling. (AU)

• Processo FAPESP: 14/50457-0 - Melatonina e a regulação do metabolismo energético: estudos básicos, clínicos e epidemiológicos
• Beneficiário: José Cipolla Neto
• Linha de fomento: Auxílio à Pesquisa - Temático
• 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
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
• Beneficiário: Jose Donato Junior
• Linha de fomento: Auxílio à Pesquisa - Temático