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Endoplasmic reticulum-localized hepatic lipase decreases triacylglycerol storage and VLDL secretion |
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| Authors: | Bruce Erickson Senthamil Paramadayalan Selvan Kerry WS Ko Karen Kelly Ariel D Quiroga Lena Li Randy Nelson Kirst King-Jones René L Jacobs Richard Lehner |
| Institution: | 1. Group on Molecular and Cell Biology of Lipids, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2S2;2. Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2S2;3. Department of Agricultural, Food & Nutritional Sciences, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2S2;4. Faculty of Science, Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E9;5. Department of Cell Biology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 |
| Abstract: | Hepatic triacylglycerol levels are governed through synthesis, degradation and export of this lipid. Here we demonstrate that enforced expression of hepatic lipase in the endoplasmic reticulum in McArdle RH7777 hepatocytes resulted in a significant decrease in the incorporation of fatty acids into cellular triacylglycerol and cholesteryl ester accompanied by attenuation of secretion of apolipoprotein B-containing lipoproteins. Hepatic lipase-mediated depletion of intracellular lipid storage increased the expression of peroxisome proliferator-activated receptor α and its target genes and augmented oxidation of fatty acids. These data show that 1) hepatic lipase is active in the endoplasmic reticulum and 2) intracellular hepatic lipase modulates cellular lipid metabolism and lipoprotein secretion. |
| Keywords: | apoB apolipoprotein B ATGL adipose triglyceride lipase CE cholesteryl ester DG diacylglycerol ER endoplasmic reticulum E600 diethyl-p-nitrophenylphosphate FA fatty acid HL hepatic lipase HL-R ER-retained hepatic lipase McA McArdle-RH7777 PBS phosphate-buffered saline MTP microsomal triglyceride transfer protein OA oleic acid PC phosphatidylcholine PDI protein disulfide isomerase PL phospholipids Ppia cyclophilin R12 McArdle cells expressing HL-R TG triacylglycerol VLDL very-low density lipoprotein |
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