Fibroblast Growth Factor 21 (Fgf21) Gene Expression Is Elevated in the Liver of Mice Fed a High-Carbohydrate Liquid Diet and Attenuated by a Lipid Emulsion but Is Not Upregulated in the Liver of Mice Fed a High-Fat Obesogenic Diet.
Fibroblast Growth Factor 21 (Fgf21) Gene Expression Is Elevated in the Liver of Mice Fed a High-Carbohydrate Liquid Diet and Attenuated by a Lipid Emulsion but Is Not Upregulated in the Liver of Mice Fed a High-Fat Obesogenic Diet.
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DOI：
10.3945/jn.115.216572
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Lei Hao;Kuan-Hsun Huang;Kyoko Ito;Sudathip Sae‐tan;J. Lambert;A. Ross
中科院分区：
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作者：
Lei Hao;Kuan-Hsun Huang;Kyoko Ito;Sudathip Sae‐tan;J. Lambert;A. Ross
成纤维细胞生长因子21 （FGF21）是碳水化合物和脂质代谢的调节因子；然而，饮食对Fgf21基因表达的调控尚不完全清楚。目的研究高碳水化合物（HC）液体饮食（添加和不添加脂质乳剂（LE））以及高脂肪饮食（HFD）与低脂肪饮食（LFD）对完整小鼠肝脏中Fgf21基因表达的调控作用。方法C57BL/6雄性小鼠分别饲喂标准饲料颗粒（SFPs）、纯化HC液体饲料（热量和蛋白质充足）或含有4%或13.5%能量LE的HC液体饲料5周（实验1）或1周（实验2）。在实验3中，小鼠被喂食纯化的低脂饲料（~ 10%脂肪）或高脂饲料（~ 60%脂肪），或者喂食高脂饲料并让小鼠进入跑步轮进行自愿运动16周。结果HC小鼠肝脏Fgf21 mRNA表达量和血浆Fgf21蛋白表达量较SFP小鼠增加3.5 ~ 7倍（P < 0.001）， LE剂量依赖性减弱Fgf21表达量（P < 0.05）。16周后，肝脏Fgf21 mRNA在LFD和HFD小鼠之间没有差异，但在HFD+运动组中显著降低，低于HFD组的20% （P < 0.0001）。结论：小鼠肝脏Fgf21表达在饲喂致脂性HC饲粮1和5周时上调，而饲喂致肥性HFD饲粮16周时上调不上调，而在HC配方中添加脂肪作为LE可显著降低Fgf21基因表达和血浆Fgf21蛋白浓度。我们的研究结果支持肝脏Fgf21表达对饮食葡萄糖摄入量变化的强烈可逆反应。
BACKGROUND Fibroblast growth factor 21 (FGF21) is a regulator of carbohydrate and lipid metabolism; however, the regulation of Fgf21 gene expression by diet remains incompletely understood. OBJECTIVE We investigated the effect of a high-carbohydrate (HC) liquid diet, with and without supplementation with a lipid emulsion (LE), and of a high-fat diet (HFD) compared with a low-fat diet (LFD) on the regulation of Fgf21 gene expression in the liver of intact mice. METHODS C57BL/6 male mice were fed standard feed pellets (SFPs), a purified HC liquid diet (adequate in calories and protein), or an HC liquid diet containing an LE at either 4% or 13.5% of energy for 5 wk (Expt. 1) or 1 wk (Expt. 2). In Expt. 3, mice were fed a purified LFD (∼10% fat) or HFD (∼60% fat) or were fed an HFD and given access to a running wheel for voluntary exercise for 16 wk. RESULTS Fgf21 mRNA in liver and FGF21 protein in plasma were increased by 3.5- to 7-fold in HC mice compared with SFP mice (P < 0.001), whereas the LE dose-dependently attenuated the induction of Fgf21 expression (P < 0.05). After 16 wk, hepatic Fgf21 mRNA did not differ between LFD and HFD mice but was dramatically reduced in the HFD+exercise group to <20% of the level in the HFD group (P < 0.0001). CONCLUSIONS In mice, hepatic Fgf21 expression was upregulated by 1 and 5 wk of feeding a lipogenic HC diet but not by 16 wk of feeding an obesogenic HFD, whereas the addition of fat as an LE to the HC formula significantly reduced Fgf21 gene expression and the plasma FGF21 protein concentration. Our results support a strong and reversible response of hepatic Fgf21 expression to shifts in dietary glucose intake.