Arnould 2018 MiP2018b

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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

COST Action MitoEAGLE

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

Arnould Figure b MiP2018.jpg
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.