title: Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.
abstract: Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.
authors: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
authors: Hiromi
authors: H
authors: Ii
authors: Naoki
authors: N
authors: Yokoyama
authors: Shintaro
authors: S
authors: Yoshida
authors: Kae
authors: K
authors: Tsutsumi
authors: Shinji
authors: S
authors: Hatakeyama
authors: Takashi
authors: T
authors: Sato
authors: Keiichi
authors: K
authors: Ishihara
authors: Satoshi
authors: S
authors: Akiba
mesh_terms: D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D054513:Group IV Phospholipases A2 / Q000172:deficiency* / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism
chemical_list: D054392:Adipokines; D004041:Dietary Fats; D008074:Lipoproteins; C516390:Pla2g4a protein, mouse; D014280:Triglycerides; D054513:Group IV Phospholipases A2; D015232:Dinoprostone