Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore.
Nat Metab. 2024 Apr;6(4):639-650. doi: 10.1038/s42255-024-00986-0. Epub 2024 Apr 26.
Thyroid hormones (THs) are key hormones that regulate development and metabolism in mammals. In man, the major target tissues for TH action are the brain, liver, muscle, heart, and adipose tissue. Defects in TH synthesis, transport, metabolism, and nuclear action have been associated with genetic and endocrine diseases in man. Over the past few years, there has been renewed interest in TH action and the therapeutic potential of THs and thyromimetics to treat several metabolic disorders such as hypercholesterolemia, dyslipidaemia, non-alcoholic fatty liver disease (NAFLD), and TH transporter defects. Recent advances in the development of tissue and TH receptor isoform-targeted thyromimetics have kindled new hope for translating our fundamental understanding of TH action into an effective therapy. This review provides a concise overview of the historical development of our understanding of TH action, its physiological and pathophysiological effects on metabolism, and future therapeutic applications to treat metabolic dysfunction.
甲状腺激素(THs)是调节哺乳动物发育和代谢的关键激素。在人类中,TH 作用的主要靶组织是脑、肝、肌肉、心脏和脂肪组织。TH 合成、转运、代谢和核作用的缺陷与人类的遗传和内分泌疾病有关。在过去的几年中,人们对 TH 作用以及 TH 和甲状腺刺激素治疗几种代谢紊乱(如高胆固醇血症、血脂异常、非酒精性脂肪肝疾病(NAFLD)和 TH 转运蛋白缺陷)的治疗潜力重新产生了兴趣。在组织和 TH 受体亚型靶向甲状腺刺激剂的开发方面的最新进展,为将我们对 TH 作用的基本理解转化为有效的治疗方法带来了新的希望。本文综述了我们对 TH 作用的认识的历史发展,及其对代谢的生理和病理生理影响,以及未来治疗代谢功能障碍的应用。