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Ligand‐induced expression of peroxisome proliferator‐activated receptor α and activation of fatty acid oxidation enzymes in fatty liver
Author(s) -
Akbiyik F.,
Cinar K.,
Demirpence E.,
Ozsullu T.,
Tunca R.,
Haziroglu R.,
Yurdaydin C.,
Uzunalimoglu O.,
Bozkaya H.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01359.x
Subject(s) - clofibrate , peroxisome , medicine , endocrinology , peroxisome proliferator activated receptor , peroxisome proliferator activated receptor alpha , beta oxidation , catalase , chemistry , fatty acid , receptor , biology , biochemistry , metabolism , oxidative stress , nuclear receptor , gene , transcription factor
Background Peroxisome proliferator‐activated receptor alpha (PPARα) regulates lipid metabolism upon activation by ligands. Peroxisome proliferator‐activated receptor α may play a role in the pathogenesis of fatty liver disease. The aim of this study was to assess the PPARα expression pattern and mitochondrial/peroxisomal enzyme activities in response to high fat diet (HFD) and clofibrate, a well known PPARα ligand. Materials and methods Four groups of Wistar‐Albino rats were included: (1) rats fed a control diet (CD) for 6 weeks, (2) rats fed CD (6 weeks) plus clofibrate (last 2 weeks), (3) rats fed HFD for 6 weeks, and (4) rats fed HFD (6 weeks) plus clofibrate (last 2 weeks). Peroxisome proliferator‐activated receptor α expression was evaluated by immunohistochemistry. Fatty acid β‐oxidation (peroxisomal‐acyl‐CoA‐oxidase and mitochondrial‐acyl‐CoA‐dehydrogenase) and catalase enzyme activities, and malondialdehyde and glutathion levels were measured spectrophotometrically in liver tissues. Results All animals were fed HFD but only 2/12 animals were fed HFD plus clofibrate‐developed fatty liver. Both HFD and clofibrate induced PPARα expression, clofibrate induction being more prominent than HFD. Clofibrate plus HFD did not further increase PPARα expression. Activities of peroxisomal‐acyl‐CoA‐oxidase and mitochondrial‐acyl‐CoA‐dehydrogenase enzymes were not induced by HFD alone. Clofibrate increased the activity of these enzymes in both CD‐ and HFD‐fed animals. However, an increase of acyl‐CoA‐oxidase activity was blunted in rats fed HFD. Catalase activity and malondialdehyde levels were increased but glutathion levels were unchanged in rats fed HFD plus clofibrate. Conclusions Clofibrate was a more potent inducer of PPARα expression than HFD in our rat fatty liver model. The finding of blunted peroxisomal enzyme response to clofibrate in fatty livers suggests that alterations in postreceptor events may exist and further contribute to liver steatosis. Clofibrate seems to stabilize glutathion content and this might contribute to the prevention of liver steatosis.