Chamulitrat, Walee and Jansakun, Chutima and Li, Huili and Liebisch, Gerhard (2020) Rescue of Hepatic Phospholipid Remodeling Defect in iPLA(2)beta-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver. BIOMOLECULES, 10 (9): 1332. ISSN 2218-273X
Full text not available from this repository. (Request a copy)Abstract
Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA(2)beta or PLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. The ubiquitously expressed iPLA(2)beta catalyzes the hydrolysis of phospholipids (PLs) to generate a fatty acid and a lysoPL. We studied the role of iPLA(2)beta on PL metabolism in non-alcoholic fatty liver disease (NAFLD). By using global deletion iPLA(2)beta-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. iPLA(2)beta deficiency rescued these decreases in obese, but not in non-obese, NAFLD models. iPLA(2)beta deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob (sic) 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 iPLA(2)beta-null mice was critical for the protection against NAFLD and obesity. However, iPLA(2)beta deletion in specific cell types such as macrophages may render liver inflammation and fibrosis, independent of steatosis protection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH-THROUGHPUT QUANTIFICATION; DIET-INDUCED OBESITY; ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; METABOLIC SYNDROME; GENETIC PREDISPOSITION; INFLAMMATION MARKERS; CHOLESTERYL ESTER; DIABETES-MELLITUS; PREVENTS OBESITY; PLA2G6; fatty liver; phospholipid remodeling; diet-induced obesity; morbidly obesity; choline and methionine deficiency |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Petra Gürster |
| Date Deposited: | 16 Apr 2021 05:44 |
| Last Modified: | 16 Apr 2021 05:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43880 |
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