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小分子通过改善脂肪代谢诱导棕色脂肪组织产热的临床应用潜力。

Clinical Application Potential of Small Molecules that Induce Brown Adipose Tissue Thermogenesis by Improving Fat Metabolism.

机构信息

505876Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.

63136Hualien Tzu Chi Hospital, Hualien, Taiwan.

出版信息

Cell Transplant. 2020 Jan-Dec;29:963689720927394. doi: 10.1177/0963689720927394.

Abstract

Mammalian fat comprises white and brown adipose tissue (WAT and BAT, respectively). WAT stores energy, whereas BAT is used for thermogenesis. In recent years, the incidence of obesity and its associated disorders have increased tremendously. Considering the thermogenic capacity and decreased levels of BAT with increasing age, BAT can be used as a suitable therapeutic target for the treatment of obesity and diabetes. In several studies, using positron emission tomography and computed tomography images, adult humans have been shown to have functional BAT in interscapular fat. Results of these basic research studies on BAT have shed light on the new components of transcriptional regulation and the role of hormones in stimulating BAT growth and differentiation. In this review article, we have summarized the thermogenic regulators identified in the past decades by focusing on peroxisome proliferator-activated receptor gamma/uncoupling protein 1 activators, branched-chain amino acids, fatty acids (lipokine), and adenosine monophosphate-activated protein kinase mediators. We have also presented the progress of a few ongoing clinical trials aimed at the treatment of obesity and its associated metabolic disorders. The main purpose of this review was to provide a comprehensive introduction to the latest knowledge of the representative thermogenic regulators for the treatment of obesity. The fat combustion capacity of BAT may have great potential and can be considered as a suitable target for the therapeutic application of drugs from bench-to-bed treatment of obesity and the associated diseases.

摘要

哺乳动物脂肪包括白色和棕色脂肪组织(分别为 WAT 和 BAT)。WAT 储存能量,而 BAT 则用于产热。近年来,肥胖及其相关疾病的发病率急剧上升。考虑到 BAT 的产热能力和随年龄增长而降低的水平,BAT 可作为治疗肥胖和糖尿病的合适治疗靶点。在几项研究中,使用正电子发射断层扫描和计算机断层扫描图像显示,成年人类肩胛间脂肪中有功能性 BAT。这些关于 BAT 的基础研究结果揭示了转录调控的新成分以及激素在刺激 BAT 生长和分化中的作用。在这篇综述文章中,我们通过重点关注过氧化物酶体增殖物激活受体γ/解偶联蛋白 1 激活剂、支链氨基酸、脂肪酸(脂肪因子)和单磷酸腺苷激活蛋白激酶调节剂,总结了过去几十年中发现的产热调节剂。我们还介绍了一些正在进行的旨在治疗肥胖及其相关代谢紊乱的临床试验的进展。本文的主要目的是为治疗肥胖的代表性产热调节剂的最新知识提供全面介绍。BAT 的脂肪燃烧能力可能具有很大的潜力,可以被认为是从肥胖症的基础治疗到药物治疗的肥胖及其相关疾病的治疗应用的合适靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6533/7563884/b7976aeb3bc5/10.1177_0963689720927394-fig1.jpg

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