MiP : 13th International Meeting of Mitochondrial Physiology and Pathology: MitoEAGLE-Cost Action

Activity: Talk or presentation typesInvited talk

Description

A 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
E-Mail: thierry.arnould@unamur.be

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 [1] 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 [2]. 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.

[1] 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.
[2] 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.

Period18 Sep 201821 Sep 2018
Event title MiP : 13th International Meeting of Mitochondrial Physiology and Pathology: MitoEAGLE-Cost Action
Event typeMeeting
Conference number13th
LocationJurmala, Latvia