Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Padmanabha, Das, KM; Wechselberger, L; Liziczai, M; De, la, Rosa, Rodriguez, M; Grabner, GF; Heier, C; Viertlmayr, R; Radler, C; Lichtenegger, J; Zimmermann, R; Borst, JW; Zechner, R; Kersten, S; Oberer, M.
Hypoxia-inducible lipid droplet-associated protein inhibits adipose triglyceride lipase.
J Lipid Res. 2018; 59(3): 531-541. Doi: 10.1194/jlr.M082388 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Grabner Gernot
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: 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.
Find related publications in this database (using NLM MeSH Indexing): Adipocytes - enzymology; Adipose Tissue - enzymology; Humans - administration & dosage; Lipase - antagonists & inhibitors, metabolism; Neoplasm Proteins - metabolism; Triglycerides - metabolism
Find related publications in this database (Keywords): hypoxia-inducible gene-2; intracellular lipolysis; adipocytes; lipolysis and fatty acid metabolism; triglycerides