[1]Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
[2]Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Canada.
[3]College of Life Science, Chongqing Normal University, Chongqing, China.
Genome-wide association studies suggest that plasma triacylglyceride (TAG) in humans was associated with variation in the PLA2G6 locus, a gene that encodes calcium-independent phospholipase A2 (iPLA2 β). The objective of the present study is to understand the impact of genetic inactivation of iPLA2 β on hepatic TAG metabolism in C57BL/6 mice.;Male iPLA2 β (+) (/-) mice were backcrossed with female iPLA2 β (-/-) mice for up to 10 generations prior to experiments. Lipid and lipoprotein metabolism from plasma, hepatocytes, thigh subcutaneous adipose and thigh skeletal muscle tissues of the mice were determined under various experimental conditions.;The iPLA2 β (-/-) mice, either male or female as compared with iPLA2 β (+) (/) (+) littermates, showed no change in fasted or postprandial plasma TAG or total cholesterol at young (12-15 weeks) or old (40-44 weeks) ages under chow diet or high-fat diet (HFD) conditions. However, fractionation of plasma lipoproteins showed that under HFD conditions, there was a significant increase (by 40%) in apoB-100 association with VLDL1 fractions in iPLA2 β (-/-) mice as compared with iPLA2 β (+) (/) (+) littermates. There was no significant difference in triglyceride or cholesterol contents in the liver, muscle, or adipose tissue between iPLA2 β (-/-) and iPLA2 β (+/+) littermates. Metabolic labeling experiments with cultured primary hepatocytes isolated from iPLA2 β (-/-) mice also showed 2-fold increase in the secretion of [(35)S]methionine-labeled apoB-100 in VLDL1 fractions as compared with that from iPLA2 β (+) (/) (+) hepatocytes. Likewise, secretion of [(3)H]palmitate-labeled TAG from the iPLA2 β (-/-) hepatocytes was increased by 2-fold.;Although iPLA2 β may play a role in TAG-rich VLDL1 production from cultured hepatocytes, there is no evidence that inactivation of iPLA2 β would lead to dyslipidemia in mice in vivo.;
(8.0+极速模式)