Service of Endocrinology, University Clinical Hospital La Paz, Madrid, Spain.
Department of Cellular and Structural Biology, University of Texas Health Science at San Antonio, San Antonio, TX, USA.
J Pineal Res. 2018 May;64(4):e12472. doi: 10.1111/jpi.12472. Epub 2018 Mar 25.
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.
褪黑素限制了啮齿动物的肥胖而不影响食物摄入和活动，表明其具有产热作用。先前我们证明，褪黑素可使 Zücker 糖尿病肥胖（ZDF）大鼠的皮下脂肪褐变。其他研究表明，褪黑素是一种信号，可以增加啮齿动物的棕色脂肪组织（BAT）质量和功能。然而，直接证明褪黑素对新募集的 BAT 的产热特性（解偶联线粒体）仍然缺乏。因此，在这项工作中，我们研究了褪黑素是否能招募 ZDF 大鼠的产热 BAT。将 Zücker 瘦（ZL）和 ZDF 动物分为两组，对照组（C）和口服褪黑素（M）治疗 6 周。C-ZDF 动物的线粒体质量、柠檬酸合酶（CS）活性以及呼吸链复合物 I 和 IV 均低于 C-ZL 动物（P<0.001）。褪黑素治疗增加了 ZDF 大鼠的 BAT 重量（P<0.001）。此外，它还增加了线粒体质量（P<0.01）以及 CS 和复合物 I 和 IV 的活性（P<0.001），无论是在 ZDF 还是 ZL 大鼠中。BAT 中的解偶联蛋白 1（UCP1）mRNA 和蛋白水平在肥胖大鼠中降低了 50%。此外，G 二磷酸（GDP）结合在 ZDF 大鼠中低于瘦大鼠（P<0.01）。褪黑素治疗肥胖大鼠恢复了 UCP1 的表达和 GDP 结合水平，达到瘦大鼠的水平，并使冷暴露的产热反应敏感化。这些数据表明，褪黑素可招募 ZDF 大鼠的产热 BAT。这可能有助于褪黑素控制体重和代谢益处。
