Arnould 2018 MiP2018b

A form of autophagy triggers lipolysis in 3T3-L1 adipocytes exposed to a mitochondrial uncoupling.

Link: MiP2018

Arnould T, Demine S, Tejerina S, Bihin B, Thiry M, Reddy N, Raes M, Renard P, Jadot M (2018)

Event: MiP2018

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.

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 [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.

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.

• Bioblast editor: Plangger M, Kandolf G

Labels: Pathology: Obesity 

Organism: Mouse  Tissue;cell: Fat, Fibroblast  Preparation: Intact cells 

Regulation: Uncoupler  Coupling state: ET 

Affiliations

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)

1. URBC-NARILIS, Univ Namur
2. Lab Cell Biology, GIGA-R, Univ Liège
3. URPhyM-NARILIS, Univ Namur
4. Center Diabetes Research, Univ Libre Bruxelles; Belgium
5. EAT-Eppendorf Array Technology. - thierry.arnould@unamur.be

Figures

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.

References

1. 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.
2. 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.