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

Biomolecules. 2020 Sep 17;10(9):1332. doi: 10.3390/biom10091332.


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.

Keywords: PLA2G6; choline and methionine deficiency; diet-induced obesity; fatty liver; morbidly obesity; phospholipid remodeling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Fibrosis
  • Group VI Phospholipases A2 / genetics
  • Group VI Phospholipases A2 / metabolism*
  • Inflammation / genetics
  • Inflammation / metabolism
  • Liver / metabolism*
  • Liver / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / genetics
  • Obesity / metabolism*
  • Phospholipids / metabolism*


  • Phospholipids
  • Group VI Phospholipases A2
  • Pla2g6 protein, mouse