Beranger Guillaume E, Karbiener Michael, Barquissau Valentin, Pisani Didier F, Scheideler Marcel, Langin Dominique, Amri Ez-Zoubir
University of Nice Sophia Antipolis, UFR Sciences, Nice, F-06108, France.
Biochim Biophys Acta. 2013 May;1831(5):905-14. doi: 10.1016/j.bbalip.2012.11.001. Epub 2012 Nov 10.
Brown adipose tissue (BAT) has long been thought to be absent or very scarce in human adults so that its contribution to energy expenditure was not considered as relevant. The recent discovery of thermogenic BAT in human adults opened the field for innovative strategies to combat overweight/obesity and associated diseases. This energy-dissipating function of BAT is responsible for adaptive thermogenesis in response to cold stimulation. In this context, adipocytes can be converted, within white adipose tissue (WAT), into multilocular adipocytes expressing UCP1, a mitochondrial protein that plays a key role in heat production by uncoupling the activity of the respiratory chain from ATP synthesis. These adipocytes have been named "brite" or "beige" adipocytes. Whereas BAT has been studied for a long time in murine models both in vivo and in vitro, there is now a strong demand for human cellular models to validate and/or identify critical factors involved in the induction of a thermogenic program within adipocytes. In this review we will discuss the different human cellular models described in the literature and what is known regarding the regulation of their differentiation and/or activation process. In addition, the role of microRNAs as novel regulators of brown/"brite" adipocyte differentiation and conversion will be depicted. Finally, investigation of both the conversion and the metabolism of white-to-brown converted adipocytes is required for the development of therapeutic strategies targeting overweight/obesity and associated diseases. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.
长期以来,人们一直认为成人棕色脂肪组织(BAT)不存在或非常稀少,因此其对能量消耗的贡献被认为无关紧要。成人产热BAT的最新发现为对抗超重/肥胖及相关疾病的创新策略开辟了领域。BAT的这种能量消耗功能负责对冷刺激的适应性产热。在这种情况下,白色脂肪组织(WAT)中的脂肪细胞可转化为表达UCP1的多泡脂肪细胞,UCP1是一种线粒体蛋白,通过使呼吸链活性与ATP合成解偶联,在产热中起关键作用。这些脂肪细胞被称为“brite”或“米色”脂肪细胞。尽管在小鼠模型中,BAT已在体内和体外被研究了很长时间,但现在迫切需要人类细胞模型来验证和/或确定参与脂肪细胞中产热程序诱导的关键因素。在这篇综述中,我们将讨论文献中描述的不同人类细胞模型,以及关于其分化和/或激活过程调控的已知信息。此外,还将描述微小RNA作为棕色/“brite”脂肪细胞分化和转化新调节因子的作用。最后,针对超重/肥胖及相关疾病的治疗策略的开发需要对白色脂肪细胞向棕色脂肪细胞的转化和代谢进行研究。本文是名为“棕色和白色脂肪:从信号传导到疾病”的特刊的一部分。