Rescue of Hepatic Phospholipid Remodeling Defectin iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver.

Walee Chamulitrat, Chutima Jansakun, Huili Li, Gerhard Liebisch

Biomolecules 2020 Sep 17

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Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β orPLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. Theubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fattyacid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liverdisease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mousemodels; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) aswell as feeding with methionine- and choline-deficient (MCD) diet (representing non-obeseNAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acidsand a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLDmodels. iPLA2β deficiency rescued these decreases in obese, but not in non-obese, NAFLD models.iPLA2β deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob › HFD »MCD. Liver inflammation was not protected in HFD NAFLD, and that liver fibrosis was evenexaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observedin iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2βdeletion in specific cell types such as macrophages may render liver inflammation and fibrosis,independent of steatosis protection.

Citation

Walee Chamulitrat, Chutima Jansakun, Huili Li, Gerhard Liebisch. Rescue of Hepatic Phospholipid Remodeling Defectin iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver. Biomolecules. 2020 Sep 17;10(9)