Brite/beige fat and UCP1-is it thermogenesis?

Brite/beige fat and UCP1-is it thermogenesis?
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DOI:
10.1016/j.bbabio.2014.02.008
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发表时间:
2014-07-01
影响因子:
4.3
通讯作者:
Jastroch, Martin
Jastroch, Martin
中科院分区:
生物学2区
文献类型:
--
作者:
Keipert, Susanne;Jastroch, Martin

文献摘要

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几十年来,人们已经知道存在两种不同类型的脂肪组织,它们具有相反的功能。白色脂肪组织(WAT)是能量储存的主要组织,而棕色脂肪组织(BAT)将能量作为热量耗散,并且是非颤抖性体温调节所需的。在过去的几年里,第三种类型的脂肪细胞被确定,称为brite(“棕色和白色”)或米色脂肪细胞。然而,它们的生理控制和作用尚未完全阐明。浅褐色/米色脂肪细胞对全身代谢具有积极影响,这通常由浅褐色/米色脂肪细胞的产热作用来解释;尽管尚未直接测量产热作用,但主要通过典型产热基因(如解偶联蛋白1(UCP 1))的基因表达数据来推断。在这里,我们批判性地审查功能的证据,为brite/米色脂肪细胞的产热潜力,导致的结论,brite/米色脂肪细胞的生物能量学的直接测量,超越基因调控,是关键的量化其产热潜力。特别地,我们举例说明了在体外分离的皮下脂肪细胞的布朗宁期间UCP 1 mRNA的大量诱导并没有反映在细胞生物能量学的显著改变中。在此,我们证明,增加线粒体呼吸响应β-肾上腺素能刺激可以是独立的UCP 1。使用表达UCP 1的HEK 293细胞,我们展示了如何通过在完整细胞中充分激活来直接评估UCP 1功能。最后,我们提供了一个指南,解释UCP 1活性和陷阱,仅使用呼吸测量。米色脂肪细胞生物能量学的功能分析将有助于描绘产热布朗宁的影响,可能阐明额外的生理作用及其对全身代谢的贡献,突出未来研究的可能途径。本文是题为:第18届欧洲生物能源会议特刊的一部分。(C)2014爱思唯尔有限公司版权所有。
The presence of two distinct types of adipose tissue, which have opposing functions, has been known for decades. White adipose tissue (WAT) is the main tissue of energy storage, while brown adipose tissue (BAT) dissipates energy as heat and is required for non-shivering thermoregulation. In the last few years, a third type of adipocyte was identified, termed the brite ("brown and white") or beige adipocyte. Their physiological control and role, however, are not fully clarified. Brite/beige adipocytes have a positive impact on systemic metabolism that is generally explained by the thermogenesis of brite/beige adipocytes; although thermogenesis has not been directly measured but is mostly inferred by gene expression data of typical thermogenic genes such as uncoupling protein 1 (UCP1). Here we critically review functional evidence for the thermogenic potential of brite/beige adipocytes, leading to the conclusion that direct measurements of brite/beige adipocyte bioenergetics, beyond gene regulation, are pivotal to quantify their thermogenic potential. In particular, we exemplified that the massive induction of UCP1 mRNA during the browning of isolated subcutaneous adipocytes in vitro is not reflected in significant alterations of cellular bioenergetics. Herein, we demonstrate that increases in mitochondrial respiration in response to beta-adrenergic stimulus can be independent of UCP1. Using HEK293 cells expressing UCP1, we show how to directly assess UCP1 function by adequate activation in intact cells. Finally, we provide a guide on the interpretation of UCP1 activity and the pitfalls by solely using respiration measurements. The functional analysis of beige adipocyte bioenergetics will assist to delineate the impact of browning on thermogenesis, possibly elucidating additional physiological roles and its contribution to systemic metabolism, highlighting possible avenues for future research. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. (C) 2014 Elsevier B.V. All rights reserved.