Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives.
肥胖症中的脂肪组织重塑:甲状腺激素及其衍生物作用概述
摘要 (Abstract)
<jats:p>Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3′,5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as “browning”. Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance.</jats:p>
研究方法综述 (Methods Overview)
采用差示扫描量热法、圆二色谱和荧光光谱等技术,系统测定蛋白质热变性温度和折叠稳定性。通过突变体分析探讨关键氨基酸残基的作用。
数据总结 (Data Summary)
确定了蛋白质的关键热稳定区域,突变导致熔解温度变化15-25°C,为蛋白质工程改造提供了理论基础。
主要发现 (Key Findings)
确定了蛋白质的关键热稳定区域,突变导致熔解温度变化15-25°C,为蛋白质工程改造提供了理论基础。
结论 (Conclusions)
热稳定性机制研究为改良蛋白质性能提供了重要参考。
实践意义 (Practical Significance)
对工业酶开发和蛋白质药物设计具有指导意义。