Next Article in Journal
Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology
Next Article in Special Issue
Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate
Previous Article in Journal
Targeting Receptors on Cancer Cells with Protein Toxins
Previous Article in Special Issue
Lipid Phosphate Phosphatases and Cancer
Open AccessReview

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

1
Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
2
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(9), 1332; https://doi.org/10.3390/biom10091332
Received: 24 August 2020 / Revised: 15 September 2020 / Accepted: 15 September 2020 / Published: 17 September 2020
(This article belongs to the Special Issue Phospholipases: From Structure to Biological Function)
Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β or PLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. The ubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fatty acid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liver disease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mouse models; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) as well as feeding with methionine- and choline-deficient (MCD) diet (representing non-obese NAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acids and a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLD models. 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 even exaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observed in iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2β deletion in specific cell types such as macrophages may render liver inflammation and fibrosis, independent of steatosis protection. View Full-Text
Keywords: PLA2G6; fatty liver; phospholipid remodeling; diet-induced obesity; morbidly obesity; choline and methionine deficiency PLA2G6; fatty liver; phospholipid remodeling; diet-induced obesity; morbidly obesity; choline and methionine deficiency
Show Figures

Graphical abstract

MDPI and ACS Style

Chamulitrat, W.; Jansakun, C.; Li, H.; Liebisch, G. Rescue of Hepatic Phospholipid Remodeling Defect in iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver. Biomolecules 2020, 10, 1332.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop