Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Giessen, Germany.
Lipids Health Dis. 2012 Mar 6;11:34. doi: 10.1186/1476-511X-11-34.
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 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 PPARα target genes acyl-CoA oxidase, carnitine palmitoyltransferase-1 and novel organic cation transporter 2 in the liver (P < 0.05), indicative of PPARα 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 PPARα. Induction of FGF21 could be involved in several effects observed in animals administered an oxidized fat.
成纤维细胞生长因子 21（FGF21）的表达受过氧化物酶体增殖物激活受体α（PPARα）诱导，最近被鉴定为一种新型代谢调节剂，在葡萄糖稳态、脂代谢、胰岛素敏感性和肥胖中发挥着关键作用。先前的研究表明，氧化脂肪的给药会导致肝脏中 PPARα 的激活。因此，本研究假设氧化脂肪的喂养会导致肝脏中 FGF21 的诱导。
将 24 头杂交猪分为两组，每组 12 头，分别用营养充足的饮食喂养新鲜油菜籽油或在 175°C 下加热 72 小时制备的氧化油菜籽油。
与对照组相比，氧化脂肪喂养的猪肝脏中 FGF21 的 mRNA 丰度和蛋白浓度显著增加（P < 0.05），血浆中 FGF21 的蛋白浓度也有增加的趋势（P < 0.1）。此外，氧化脂肪喂养的猪肝脏中 PPARα 靶基因酰基辅酶 A 氧化酶、肉碱棕榈酰转移酶-1 和新型有机阳离子转运体 2 的转录水平升高（P < 0.05），表明 PPARα 激活。
本研究首次表明，氧化脂肪的给药会诱导肝脏中 FGF21 的表达，可能通过激活 PPARα介导。FGF21 的诱导可能参与了给予氧化脂肪的动物中观察到的几种效应。
