Rabiee Atefeh
Department of Chemical and Systems Biology, Stanford University, Stanford, CA, United States.
Front Endocrinol (Lausanne). 2020 Sep 4;11:634. doi: 10.3389/fendo.2020.00634. eCollection 2020.
Understanding the mammalian energy balance can pave the way for future therapeutics that enhance energy expenditure as an anti-obesity and anti-diabetic strategy. Several studies showed that brown adipose tissue activity increases daily energy expenditure. However, the size and activity of brown adipose tissue is reduced in individuals with obesity and type two diabetes. Humans have an abundance of functionally similar beige adipocytes that have the potential to contribute to increased energy expenditure. This makes beige adipocytes a promising target for metabolic disease therapies. While brown adipocytes tend to be stable, beige adipocytes have a high level of plasticity that allows for the rapid and dynamic induction of thermogenesis by external stimuli such as low environmental temperatures. This means that after browning stimuli have been withdrawn beige adipocytes quickly transition back to their white adipose state. The detailed molecular mechanisms regulating beige adipocytes development, function, and reversibility are not fully understood. The goal of this review is to give a comprehensive overview of beige fat development and origins, along with the transcriptional and epigenetic programs that lead to beige fat formation, and subsequent thermogenesis in humans. An improved understanding of the molecular pathways of beige adipocyte plasticity will enable us to selectively manipulate beige cells to induce and maintain their thermogenic output thus improving the whole-body energy homeostasis.
了解哺乳动物的能量平衡可为未来通过增加能量消耗来实现抗肥胖和抗糖尿病策略的治疗方法铺平道路。多项研究表明，棕色脂肪组织的活性可增加每日能量消耗。然而，肥胖和2型糖尿病患者的棕色脂肪组织大小和活性会降低。人类拥有大量功能相似的米色脂肪细胞，它们有可能促进能量消耗增加。这使得米色脂肪细胞成为代谢疾病治疗的一个有前景的靶点。虽然棕色脂肪细胞往往较为稳定，但米色脂肪细胞具有高度可塑性，能够通过外部刺激（如低环境温度）快速动态地诱导产热。这意味着在去分化刺激撤除后，米色脂肪细胞会迅速转变回白色脂肪状态。调节米色脂肪细胞发育、功能和可逆性的详细分子机制尚未完全了解。本综述的目的是全面概述米色脂肪的发育和起源，以及导致米色脂肪形成和随后人类产热的转录和表观遗传程序。对米色脂肪细胞可塑性分子途径的深入理解将使我们能够选择性地操纵米色细胞，诱导并维持其产热输出，从而改善全身能量稳态。
