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Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs.

ABSTRACT: Fibroblast growth factor 21 (FGF21), whose expression is induced by peroxisome proliferator-activated receptor ? (PPAR?), has been recently identified as a novel metabolic regulator which plays a crucial role in glucose homeostasis, lipid metabolism, insulin sensitivity and obesity. Previous studies have shown that administration of oxidized fats leads to an activation of PPAR? in the liver. Therefore, the present study investigated the hypothesis that feeding of oxidized fats causes an induction of FGF21 in the liver.Twenty four crossbred pigs were allocated to two groups of 12 pigs each and fed nutritionally adequate diets with either fresh rapeseed oil or oxidized rapeseed oil prepared by heating at a temperature of 175°C for 72 h.In pigs fed the oxidized fat mRNA abundance and protein concentrations of FGF21 in liver were significantly increased (P < 0.05), and the protein concentrations of FGF21 in plasma tended to be increased (P < 0.1) in comparison to control pigs. Moreover, pigs fed the oxidized fat had increased transcript levels of the PPAR? target genes acyl-CoA oxidase, carnitine palmitoyltransferase-1 and novel organic cation transporter 2 in the liver (P < 0.05), indicative of PPAR? activation.The present study shows for the first time that administration of an oxidized fat induces the expression of FGF21 in the liver, probably mediated by activation of PPAR?. Induction of FGF21 could be involved in several effects observed in animals administered an oxidized fat.

SUBMITTER: Varady J

PROVIDER: S-EPMC3807756 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs.

Varady Juliane J Ringseis Robert R Eder Klaus K

Lipids in health and disease 20120306

<h4>Background</h4>Fibroblast growth factor 21 (FGF21), whose expression is induced by peroxisome proliferator-activated receptor α (PPARα), has been recently identified as a novel metabolic regulator which plays a crucial role in glucose homeostasis, lipid metabolism, insulin sensitivity and obesity. Previous studies have shown that administration of oxidized fats leads to an activation of PPARα in the liver. Therefore, the present study investigated the hypothesis that feeding of oxidized fats ...[more]

PMID: 22394566

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Project description:Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4-/- mice with deficiency of the hepatobiliary phospholipid transporter. Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4-/- (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group). A total of 58 human subjects were recruited into the study, including patients with alcohol-associated liver disease (AALD; n = 31) and healthy controls (n = 27). The hepatic and ileal expressions of genes involved in bile acid metabolism, plasma FGF levels, and bile acid and its precursors 7α- and 27-hydroxycholesterol (7α- and 27-OHC) concentrations were determined. Primary mouse hepatocytes were isolated for cell culture experiments. Alcohol feeding significantly induced plasma FGF21 and decreased hepatic Cyp7a1 levels. Hepatic expression levels of Fibroblast growth factor receptor 1 (Fgfr1), Fgfr4, Farnesoid X-activated receptor (Fxr), and Small heterodimer partner (Shp) and plasma FGF15/FGF19 levels did not differ with alcohol challenge. Exogenous FGF21 treatment suppressed Cyp7a1 in a dose-dependent manner in vitro. AALD patients showed markedly higher FGF21 and lower 7α-OHC plasma levels while FGF19 did not differ. The simultaneous upregulation of FGF21 and downregulation of Cyp7a1 expressions upon chronic plus binge alcohol feeding together with the invariant plasma FGF15 and hepatic Shp and Fxr levels suggest the presence of a direct regulatory mechanism of FGF21 on bile acid homeostasis through inhibition of CYP7A1 by an FGF15-independent pathway in this ACLI model. Lay Summary: Alcohol challenge results in the upregulation of FGF21 and repression of Cyp7a1 expressions while circulating FGF15 and hepatic Shp and Fxr levels remain constant both in healthy and pre-injured livers, suggesting the presence of an alternative FGF15-independent regulatory mechanism of FGF21 on bile acid homeostasis through the inhibition of Cyp7a1.

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Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs.

Publications

Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs.

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