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KMID : 1140220130180030235
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대한암예방학회지
2013 Volume.18 No. 3 p.235 ~ p.248
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Global Inactivation of the Pla2g6 Gene in Mice Does Not Cause Dyslipidemia under Chow or High-fat Diet Conditions
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Zhang Li
Zhong Shumei
Li YIng
Ji Guang
Sundaram Meenakshi
Yao Zemin
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Abstract
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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 (iPLA2β). The objective of the present study is to understand the impact of genetic inactivation of iPLA2β on hepatic TAG metabolism in C57BL/6 mice.
Methods: Male iPLA2β+/? mice were backcrossed with female iPLA2β?/? 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 iPLA2β?/? mice, either male or female as compared with iPLA2β+/+ 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 iPLA2β?/? mice as compared with iPLA2β+/+ littermates. There was no significant difference in triglyceride or cholesterol contents in the liver, muscle, or adipose tissue between iPLA2β?/? and iPLA2β+/+ littermates. Metabolic labeling experiments with cultured primary hepatocytes isolated from iPLA2β?/? mice also showed 2-fold increase in the secretion of [35S]methionine-labeled apoB-100 in VLDL1 fractions as compared with that from iPLA2β+/+ hepatocytes. Likewise, secretion of [3H]palmitate-labeled TAG from the iPLA2β?/? hepatocytes was increased by 2-fold.
Conclusions: Although iPLA2β may play a role in TAG-rich VLDL1 production from cultured hepatocytes, there is no evidence that inactivation of iPLA2β would lead to dyslipidemia in mice in vivo.
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KEYWORD
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Phospholipase A2, iPLA2β, Triglyceride, Cholesterol, VLDL
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