Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Previously we demonstrated that melatonin browns subcutaneous fat in Zücker diabetic fatty (ZDF) rats. Other works pointed to melatonin as a signal that increases brown adipose tissue (BAT) mass and function in rodents. However, direct proof of thermogenic properties (uncoupled mitochondria) of the newly recruited BAT in response to melatonin is still lacking. Therefore, in this work, we investigated if melatonin recruits thermogenic BAT in ZDF rats. Zücker lean (ZL) and ZDF animals were subdivided into two groups, control (C) and treated with oral melatonin (M) for 6 weeks. Mitochondrial mass, activity of citrate synthase (CS), and respiratory chain complexes I and IV were lower in C‐ZDF than in C‐ZL animals (P < .001). Melatonin treatment increased BAT weight in ZDF rats (P < .001). Also, it rose mitochondrial mass (P < .01) and activities of CS and complexes I and IV (P < .001) in both, ZDF and ZL rats. Uncoupling protein 1 (UCP1) mRNA and protein were 50% lower in BAT from obese rats. Also, guanosine diphosphate (GDP) binding was lower in ZDF than in lean rats (P < .01). Melatonin treatment of obese rats restored the expression of UCP1 and GDP binding to levels of lean rats and sensitized the thermogenic response to cold exposure. These data demonstrated that melatonin recruits thermogenic BAT in ZDF rats. This may contribute to melatonin's control of body weight and its metabolic benefits.

中文翻译：

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褪黑素增加了Zücker糖尿病脂肪大鼠的棕色脂肪组织质量和功能：对肥胖控制的意义

褪黑激素可限制啮齿类动物的肥胖，而不会影响食物的摄入和活动，这表明具有产热作用。先前，我们证明了褪黑素使Zücker糖尿病脂肪（ZDF）大鼠的皮下脂肪变褐。其他工作指出褪黑激素是增加棕色脂肪组织（BAT）质量和在啮齿动物中起作用的信号。但是，仍然缺乏直接证实新近募集的BAT对褪黑激素反应的生热特性（线粒体解偶联）的直接证据。因此，在这项工作中，我们调查了褪黑激素是否在ZDF大鼠中募集了产热BAT。将Zückerlean（ZL）和ZDF动物分为对照组（C）和两组，然后口服褪黑激素（M）治疗6周。C-ZDF中的线粒体质量，柠檬酸合酶（CS）活性以及呼吸链复合体I和IV低于C-ZL动物（P  <  .001）。褪黑素治疗可增加ZDF大鼠的BAT体重（P  <  .001）。此外，在ZDF和ZL大鼠中，其线粒体质量（P  <  .01）以及CS和复合物I和IV的活性（P  <  .001）均升高。肥胖大鼠的BAT中解偶联蛋白1（UCP1）mRNA和蛋白降低了50％。此外，ZDF中的鸟苷二磷酸（GDP）结合率比瘦大鼠低（P  < .01）。肥胖大鼠的褪黑激素治疗恢复了UCP1的表达和GDP与瘦鼠水平的结合，并使对冷暴露的产热反应敏感。这些数据证明褪黑激素在ZDF大鼠中募集产热BAT。这可能有助于褪黑激素控制体重及其代谢益处。