Demine Stéphane, Tejerina Silvia, Bihin Benoît, Thiry Marc, Reddy Nagabushana, Renard Patricia, Raes Martine, Jadot Michel, Arnould Thierry
Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), Namur, Belgium.
Laboratory of Cell Biology, GIGA-R, University of Liège, Liège, Belgium.
J Cell Physiol. 2018 Feb;233(2):1247-1265. doi: 10.1002/jcp.25994. Epub 2017 Jun 15.
Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling relies on a form of autophagy as lipid droplets are captured by endolysosomal vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed to mild uncoupling provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.
肥胖的特征是白色脂肪细胞中三酰甘油过度积累。人们已经确定了各种机制，通过脂滴相关蛋白以及脂解酶来严格调控三酰甘油的储存和动员。通过诱导脂肪细胞中线粒体轻度解偶联来增加能量消耗，可能是一种颇具前景的抗肥胖策略，因为它通过尚不清楚的机制刺激脂解作用，降低脂肪组织三酰甘油含量（限制细胞肥大引起的改变），从而限制脂肪细胞肥大的不良影响。在此，对白色3T3-L1脂肪细胞中线粒体轻度解偶联诱导脂解作用所涉及的分子机制进行了表征。发现线粒体解偶联诱导的脂解作用独立于涉及脂解酶如激素敏感性脂肪酶（HSL）和脂肪甘油三酯脂肪酶（ATGL）的经典途径。最后，对线粒体解偶联的反应中增强的脂解作用依赖于一种自噬形式，因为脂滴被内溶酶体囊泡捕获。在暴露于轻度解偶联的脂肪细胞中，这种新的三酰甘油分解机制为处理被迫消耗能量的线粒体的脂肪细胞生物学提供了新的见解。
