| First Author | Zhang L | Year | 2013 |
| Journal | J Cancer Prev | Volume | 18 |
| Issue | 3 | Pages | 235-48 |
| PubMed ID | 25337551 | Mgi Jnum | J:203038 |
| Mgi Id | MGI:5523979 | Doi | 10.15430/JCP.2013.18.3.235 |
| Citation | Zhang L, et al. (2013) Global Inactivation of the Pla2g6 Gene in Mice Does Not Cause Dyslipidemia under Chow or High-fat Diet Conditions. J Cancer Prev 18(3):235-248 |
| abstractText | 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 beta). The objective of the present study is to understand the impact of genetic inactivation of iPLA2 beta on hepatic TAG metabolism in C57BL/6 mice. METHODS: Male iPLA2 beta (+) (/-) mice were backcrossed with female iPLA2 beta (-/-) 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 beta (-/-) mice, either male or female as compared with iPLA2 beta (+) (/) (+) 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 beta (-/-) mice as compared with iPLA2 beta (+) (/) (+) littermates. There was no significant difference in triglyceride or cholesterol contents in the liver, muscle, or adipose tissue between iPLA2 beta (-/-) and iPLA2 beta (+/+) littermates. Metabolic labeling experiments with cultured primary hepatocytes isolated from iPLA2 beta (-/-) 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 beta (+) (/) (+) hepatocytes. Likewise, secretion of [(3)H]palmitate-labeled TAG from the iPLA2 beta (-/-) hepatocytes was increased by 2-fold. CONCLUSIONS: Although iPLA2 beta may play a role in TAG-rich VLDL1 production from cultured hepatocytes, there is no evidence that inactivation of iPLA2 beta would lead to dyslipidemia in mice in vivo. |
