Martínez-Sánchez Noelia, Alvarez Clara V, Fernø Johan, Nogueiras Rubén, Diéguez Carlos, López Miguel
Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Department of Clinical Science, K. G. Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway.
Best Pract Res Clin Endocrinol Metab. 2014 Oct;28(5):703-12. doi: 10.1016/j.beem.2014.04.004. Epub 2014 Apr 25.
Over the past few decades, obesity and its related metabolic disorders have increased at an epidemic rate in the developed and developing world. New signals and factors involved in the modulation of energy balance and metabolism are continuously being discovered, providing potential novel drug targets for the treatment of metabolic disease. A parallel strategy is to better understand how hormonal signals, with an already established role in energy metabolism, work, and how manipulation of the pathways involved may lead to amelioration of metabolic dysfunction. The thyroid hormones belong to the latter category, with dysregulation of the thyroid axis leading to marked alterations in energy balance. The potential of thyroid hormones in the treatment of obesity has been known for decades, but their therapeutic use has been hampered because of side-effects. Data gleaned over the past few years, however, have uncovered new features at the mechanisms of action involved in thyroid hormones. Sophisticated neurobiological approaches have allowed the identification of specific energy sensors, such as AMP-activated protein kinase and mechanistic target of rapamycin, acting in specific groups of hypothalamic neurons, mediating many of the effects of thyroid hormones on food intake, energy expenditure, glucose, lipid metabolism, and cardiovascular function. More extensive knowledge about these molecular mechanisms will be of great relevance for the treatment of obesity and metabolic syndrome.
在过去几十年中，肥胖及其相关的代谢紊乱在发达国家和发展中国家呈流行趋势增加。参与能量平衡和代谢调节的新信号和因素不断被发现，为代谢疾病的治疗提供了潜在的新型药物靶点。一个并行的策略是更好地理解在能量代谢中已确立作用的激素信号如何发挥作用，以及对相关途径的操控如何可能导致代谢功能障碍的改善。甲状腺激素属于后一类，甲状腺轴的失调会导致能量平衡的显著改变。甲状腺激素在肥胖治疗中的潜力已为人所知数十年，但由于副作用，其治疗应用受到了阻碍。然而，过去几年收集的数据揭示了甲状腺激素作用机制的新特征。先进的神经生物学方法已能够识别特定的能量传感器，如AMP激活的蛋白激酶和雷帕霉素作用靶点，它们在下丘脑特定神经元群中发挥作用，介导甲状腺激素对食物摄入、能量消耗、葡萄糖、脂质代谢和心血管功能的许多影响。对这些分子机制的更广泛了解对于肥胖和代谢综合征的治疗将具有重要意义。
