title: Global Inactivation of the Pla2g6 Gene in Mice Does Not Cause Dyslipidemia under Chow or High-fat Diet Conditions.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Canada.
authors.forename: Shumei
authors.initials: S
authors.lastname: Zhong
authors.affiliation: College of Life Science, Chongqing Normal University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Canada.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Sundaram
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Canada.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Yao
keywords: Cholesterol; Phospholipase A2; Triglyceride; VLDL; iPLA2β