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Removing melatonin receptor type 1 signaling leads to selective leptin resistance in the arcuate nucleus
Author(s) -
Buonfiglio Daniella,
Tchio Cynthia,
Furigo Isadora,
Donato José,
Baba Kenkichi,
CipollaNeto José,
Tosini Gianluca
Publication year - 2019
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12580
Subject(s) - leptin , medicine , endocrinology , leptin receptor , melatonin , stat3 , phosphorylation , hypothalamus , signal transduction , energy homeostasis , receptor , stat protein , biology , chemistry , microbiology and biotechnology , obesity
Abstract 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 (MT 1 KO) 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, MT 1 KO 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 MT 1 KO mice beyond levels observed in mice injected with phosphate‐buffered saline (PBS). Furthermore, STAT3 phosphorylation within the arcuate nucleus (ARH) was decreased in MT 1 KO mice. Leptin receptor mRNA levels in the hypothalamus of MT 1 KO were significantly reduced (about 50%) compared to WT. This study shows that: (a) MT 1 deficiency causes weight gain and increased food intake; (b) a lack of MT 1 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 MT 1 signaling is an important modulator of leptin signaling.