Hypoxia-inducible lipid droplet-associated protein inhibits adipose triglyceride lipase

Journal of Lipid Research

Monika Oberer¹  Jan Willem Borst¹  Montserrat De la Rosa Rodriguez²  Krishna M. Padmanabha Das³  Roland Viertlmayr³  Sander Kersten³  Gernot F. Grabner³  Márton Liziczai³  Lisa Wechselberger³  Claudia Radler³  Christoph Heier³  Jörg Lichtenegger³  Robert Zimmermann³  Rudolf Zechner⁴ 

[1] BioTechMed-Graz, 8010 Graz, Austria;Division of Human Nutrition Wageningen University, Wageningen, The Netherlands;Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria;Laboratory of Biochemistry and Microspectroscopy Research Facility, Wageningen University, Wageningen, The Netherlands;

关键词: hypoxia-inducible gene-2;    intracellular lipolysis;    adipocytes;    lipolysis and fatty acid metabolism;    triglycerides;   

DOI  :  

来源: DOAJ

【 摘 要 】

Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance of energy homeostasis. Hypoxia-inducible lipid droplet-associated protein (HILPDA)/hypoxia-inducible gene-2 (Hig-2) has been shown to affect intracellular TAG levels, yet, the underlying molecular mechanisms are unclear. Here, we show that HILPDA inhibits adipose triglyceride lipase (ATGL), the enzyme catalyzing the first step of intracellular TAG hydrolysis. HILPDA shares structural similarity with G0/G1 switch gene 2 (G0S2), an established inhibitor of ATGL. HILPDA inhibits ATGL activity in a dose-dependent manner with an IC50 value of ∼2 μM. ATGL inhibition depends on the direct physical interaction of both proteins and involves the N-terminal hydrophobic region of HILPDA and the N-terminal patatin domain-containing segment of ATGL. Finally, confocal microscopy combined with Förster resonance energy transfer-fluorescence lifetime imaging microscopy analysis indicated that HILPDA and ATGL colocalize and physically interact intracellularly. These findings provide a rational biochemical explanation for the tissue-specific increased TAG accumulation in HILPDA-overexpressing transgenic mouse models.

【 授权许可】

Unknown