Journal article
PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle
Rachael R Mason, Ruzaidi Mokhtar, Maria Matzaris, Ahrathy Selathurai, Greg M Kowalski, Nancy Mokbel, Peter J Meikle, Clinton R Bruce, Matthew J Watt
MOLECULAR METABOLISM | ELSEVIER | Published : 2014
Abstract
Defective control of lipid metabolism leading to lipotoxicity causes insulin resistance in skeletal muscle, a major factor leading to diabetes. Here, we demonstrate that perilipin (PLIN) 5 is required to couple intramyocellular triacylglycerol lipolysis with the metabolic demand for fatty acids. PLIN5 ablation depleted triacylglycerol stores but increased sphingolipids including ceramide, hydroxylceramides and sphingomyelin. We generated perilipin 5 (Plin5)(-/-) mice to determine the functional significance of PLIN5 in metabolic control and insulin action. Loss of PLIN5 had no effect on body weight, feeding or adiposity but increased whole-body carbohydrate oxidation. Plin5 (-/-) mice develo..
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Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NIH
Awarded by CSD Consortium
Funding Acknowledgements
We thank Dirk Truman and Leanne Cotton (Monash University) for valuable advice on mouse generation and Adam Costin (Monash Micro Imaging, Monash University) for performing the electron microscopy analysis. These studies were supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (to MJW APP1047138). RRM is supported by Paul McNamee Postgraduate Scholarship and MJW and PJM are supported by research fellowships from the National Health and Medical Research Council (NHMRC, APP 606460). NIH grants to Velocigene at Regeneron Inc (U01HG004085) and The CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells for 8500 genes in the KOMP Program and archived and distributed by the KOMP Repository at UC Davis and CHORI (U42RR024244).