PMID:24511104

Citation	'Ruhanen, H, Perttilä, J Dr, Hölttä-Vuori, M Dr, Zhou, Y Dr, Yki-Järvinen, H Prof, Ikonen, E Prof, Käkelä, R Dr and Olkkonen, VM Dr (2014) PNPLA3 mediates hepatocyte triacylglycerol remodelling. J. Lipid Res. '
Abstract	The I148M substitution in PNPLA3 (PNPLA3(I148M)) determines a genetic form of non-alcoholic fatty liver disease. To elucidate the mode of PNPLA3 action in human hepatocytes, we studied effects of wild-type PNPLA3 (PNPLA3(WT)) and PNPLA3(I148M) on HuH7 cell lipidome after [(13)C]glycerol labelling, cellular turnover of [D17]oleic acid in triacylglycerols (TAGs), and subcellular distribution of the protein variants. PNPLA3(I148M) induced a net accumulation of unlabelled TAGs, but not newly synthesized total [(13)C]TAGs. Principal component analysis (PCA) revealed that both PNPLA3(WT) and PNPLA3(I148M) induced a relative enrichment of TAGs with saturated or monounsaturated fatty acids, with concurrent enrichment of polyunsaturated phosphatidylcholines. PNPLA3(WT) associated in PCA with newly synthesized [(13)C]TAGs, particularly 52:1 and 50:1, while PNPLA3(I148M) associated with similar pre-existing TAGs. PNPLA3(WT) overexpression resulted in increased [D17]oleic acid labelling of TAGs during 24 h, and after longer incubations their turnover was accelerated, effects not detected with PNPLA3(I148M). PNPLA3(I148M) localized more extensively to lipid droplets (LD) than PNPLA3(WT), suggesting that the substitution alters distribution of PNPLA3 between LD and endoplasmic reticulum/cytosol. This study reveals a function of PNPLA3 in fatty acid-selective TAG remodelling, resulting in increased TAG saturation. A defect in TAG remodelling activity likely contributes to the TAG accumulation observed in cells expressing PNPLA3(I148M).
Links	PubMed Online version:10.1194/jlr.M046607
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PLPL3		GO:0036153: triglyceride acyl-chain remodeling	ECO:0000314:		P		Fig 3	complete CACAO 9598
HUMAN:PLPL3	involved_in	GO:0036153: triglyceride acyl-chain remodeling	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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