Arnould 2018 MiP2018b
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.
3T3-L1 fibroblasts were exposed to a mild uncoupling of mitochondria triggered by 0.5 μM carbonyl cyanide-p-trifluoromethoxyphenylhydrazone FCCP or 50 μM dinitrophenol (DNP) and several biochemical assays and techniques of microscopy were used to monitor mitochondria uncoupling-induced lipolysis assessed by glycerol release.
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.
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.
Labels: Pathology: Obesity
Organism: Mouse Tissue;cell: Fat, Fibroblast Preparation: Intact cells
Regulation: Uncoupler Coupling state: ET
Arnould T(1), Demine S(4), Tejerina S(5), Bihin B(1), Thiry M(2), Reddy N(1), Raes M(1), Renard P(1) and Jadot M(3)
- URBC-NARILIS, Univ Namur
- Lab Cell Biology, GIGA-R, Univ Liège
- URPhyM-NARILIS, Univ Namur
- Center Diabetes Research, Univ Libre Bruxelles; Belgium
- EAT-Eppendorf Array Technology. - [email protected]
Figure 1. Mitochondrial uncoupling increases co-localization between lysosomes and lipid droplets. The co-localization between LDs and lysosomes was visualized by confocal microscopy in cells in which lysosomes, LDs, and nuclei were stained by LysoTracker Red (red), BODIPY 493/503 (green) and TO-PRO3 iodide (blue), respectively. White arrows indicate co-localization events between LDs and lysosomes.
- De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T (2009) Mitochondrial (dys)function in adipocyte (de)differentiation and systemic alterations. Am J Pathol 175:927-39.
- Demine S, Tejerina S, Bihin B, Thiry M, Reddy N, Renard P, Raes M, Jadot M, Arnould T (2018) Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a form of autophagy in 3T3-L1 adipocytes. J Cell Physiol 233:1247-65.