DescriptionA form of autophagy triggers lipolysis in 3T3-L1 adipocytes exposed to a mitochondrial uncoupling
Arnould T1, Demine S4, Tejerina S5, Bihin B1, Thiry M2, Reddy N1, Raes M1, Renard P1 and Jadot M3.
1 URBC-NARILIS, University of Namur (UNamur), Belgium, 2 Laboratory of Cell Biology, GIGA-R, University of Liège, Belgium, 3 URPhyM-NARILIS, University of Namur (UNamur), Belgium, 4 Center for Diabetes Research, Université Libre de Bruxelles, Belgium, 5 EAT-Eppendorf Array Technology
Introduction: Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the 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 by stimulating lipolysis through yet unknown mechanisms, limiting the systemic adverse effects of adipocyte hypertrophy.
Methods: 3T3-L1 fibroblasts were exposed to a mild uncoupling of mitochondria triggered by 0.5 M carbonyl cyanide-p-trifluoromethoxyphenylhydrazone FCCP or 50 M dinitrophenol (DNP) and several biochemical assays and techniques of microscopy were used to monitor mitochondria uncoupling-induced lipolysis assessed by glycerol release.
Results: Mitochondrial uncoupling-induces lipolysis but does not involve lipolytic enzymes such as hormone-sensitive lipase (HSL) and adipose ATGL . Enhanced lipolysis relies on a form of autophagy as lipid droplets are directly captured by endolysosomal vesicles. In addition, lysosomal poisoning and inhibition of microautophagy by valinomycin inhibit lipolysis.
Conclusions: A new mechanism of triacylglycerol breakdown was identified in adipocytes exposed to mild uncoupling that provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.
 De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T. Mitochondrial (dys)function in adipocyte (de)differentiation and systemic alterations. Am J Pathol. 2009;175(3):927-39.
 Demine S, Tejerina S, Bihin B, Thiry M, Reddy N, Renard P, Raes M, Jadot M, Arnould T. Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a form of autophagy in 3T3-L1 adipocytes. J Cell Physiol. 2018 ;233(2):1247-1265.
|Period||18 Sep 2018 → 21 Sep 2018|
|Event title||MiP : 13th International Meeting of Mitochondrial Physiology and Pathology: MitoEAGLE-Cost Action|