Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United States.
Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States.
Front Endocrinol (Lausanne). 2021 Apr 9;12:653179. doi: 10.3389/fendo.2021.653179. eCollection 2021.
Obesity is a global health problem and a major risk factor for several metabolic conditions including dyslipidemia, diabetes, insulin resistance and cardiovascular diseases. Obesity develops from chronic imbalance between energy intake and energy expenditure. Stimulation of cellular energy burning process has the potential to dissipate excess calories in the form of heat the activation of uncoupling protein-1 (UCP1) in white and brown adipose tissues. Recent studies have shown that of transforming growth factor-β (TGF-β) signaling pathway significantly contributes to the development of obesity, and blockade or inhibition is reported to protect from obesity by promoting white adipose browning and increasing mitochondrial biogenesis. Identification of novel compounds that activate beige/brown adipose characteristics to burn surplus calories and reduce excess storage of fat are actively sought in the fight against obesity. In this review, we present recent developments in our understanding of key modulators of TGF-β signaling pathways including follistatin (FST) and myostatin (MST) in regulating adipose browning and brown adipose mass and activity. While MST is a key ligand for TGF-β family, FST can bind and regulate biological activity of several TGF-β superfamily members including activins, bone morphogenic proteins (BMP) and inhibins. Here, we review the literature supporting the critical roles for FST, MST and other proteins in modulating TGF-β signaling to influence beige and brown adipose characteristics. We further review the potential therapeutic utility of FST for the treatment of obesity and related metabolic disorders.
肥胖是一个全球性的健康问题，也是包括血脂异常、糖尿病、胰岛素抵抗和心血管疾病在内的多种代谢性疾病的主要危险因素。肥胖是由能量摄入和能量消耗之间的慢性失衡引起的。刺激细胞能量燃烧过程有可能以热量的形式消耗多余的卡路里，这是通过激活白色和棕色脂肪组织中的解偶联蛋白 1 (UCP1) 实现的。最近的研究表明，转化生长因子-β (TGF-β) 信号通路的激活显著促进了肥胖的发展，并且据报道通过促进白色脂肪棕色化和增加线粒体生物发生来阻断或抑制该信号通路可以预防肥胖。人们正在积极寻找能够激活米色/棕色脂肪特性以燃烧多余卡路里并减少脂肪过度储存的新型化合物，以对抗肥胖。在这篇综述中，我们介绍了我们对 TGF-β 信号通路关键调节剂的最新理解，包括卵泡抑素 (FST) 和肌肉生长抑制素 (MST) 在调节脂肪棕色化和棕色脂肪质量和活性方面的作用。虽然 MST 是 TGF-β 家族的关键配体，但 FST 可以结合并调节包括激活素、骨形态发生蛋白 (BMP) 和抑制素在内的几种 TGF-β 超家族成员的生物学活性。在这里，我们回顾了支持 FST、MST 和其他蛋白质在调节 TGF-β 信号以影响米色和棕色脂肪特征方面的关键作用的文献。我们进一步综述了 FST 在治疗肥胖和相关代谢性疾病方面的潜在治疗用途。
