Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice.
Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice.
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DOI：
10.2337/db08-0392
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发表时间：
2009-01
期刊：
影响因子：
7.7
通讯作者：
Véniant MM
中科院分区：
文献类型：
--
作者：
Xu J;Lloyd DJ;Hale C;Stanislaus S;Chen M;Sivits G;Vonderfecht S;Hecht R;Li YS;Lindberg RA;Chen JL;Jung DY;Zhang Z;Ko HJ;Kim JK;Véniant MM
成纤维细胞生长因子21（FGF 21）已成为葡萄糖和脂质代谢的重要代谢调节剂。本研究的目的是评估FGF 21在能量代谢中的作用，并在高脂饮食诱导的肥胖（DIO）模型中提供其降糖降脂作用的机制见解。研究设计和方法-DIO或正常瘦小鼠用载体或重组鼠FGF 21处理。监测代谢参数，包括体重、葡萄糖和脂质水平，并分析肝脏基因表达。采用间接量热法和高胰岛素-正葡萄糖钳夹技术评估能量代谢和胰岛素敏感性。由于总能量消耗和身体活动水平的显著增加，DIO小鼠中的IGBTS-FGF 21剂量依赖性地降低体重和全身脂肪量。FGF 21还降低血糖、胰岛素和脂质水平，并逆转肝脂肪变性。肝脏甘油三酯水平的显著降低与FGF 21抑制核固醇调节元件结合蛋白-1以及参与脂肪酸和甘油三酯合成的多种基因的表达相关。FGF 21还显著改善了瘦小鼠和DIO小鼠的肝脏和外周胰岛素敏感性，而与体重和肥胖的减轻无关。结论：FGF 21可纠正DIO小鼠的多种代谢紊乱，并有可能成为治疗肝脂肪变性、肥胖和2型糖尿病的有效药物。
OBJECTIVE—Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator of glucose and lipid metabolism. The aims of the current study are to evaluate the role of FGF21 in energy metabolism and to provide mechanistic insights into its glucose and lipid-lowering effects in a high-fat diet–induced obesity (DIO) model. RESEARCH DESIGN AND METHODS—DIO or normal lean mice were treated with vehicle or recombinant murine FGF21. Metabolic parameters including body weight, glucose, and lipid levels were monitored, and hepatic gene expression was analyzed. Energy metabolism and insulin sensitivity were assessed using indirect calorimetry and hyperinsulinemic-euglycemic clamp techniques. RESULTS—FGF21 dose dependently reduced body weight and whole-body fat mass in DIO mice due to marked increases in total energy expenditure and physical activity levels. FGF21 also reduced blood glucose, insulin, and lipid levels and reversed hepatic steatosis. The profound reduction of hepatic triglyceride levels was associated with FGF21 inhibition of nuclear sterol regulatory element binding protein-1 and the expression of a wide array of genes involved in fatty acid and triglyceride synthesis. FGF21 also dramatically improved hepatic and peripheral insulin sensitivity in both lean and DIO mice independently of reduction in body weight and adiposity. CONCLUSIONS—FGF21 corrects multiple metabolic disorders in DIO mice and has the potential to become a powerful therapeutic to treat hepatic steatosis, obesity, and type 2 diabetes.
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DOI：
10.1073/pnas.0701600104
发表时间：
2007-05-01
影响因子：
11.1
作者：
Ogawa, Yasushi;Kurosu, Hiroshi;Kuro-o, Makoto
通讯作者：
Kuro-o, Makoto
影响因子：
5.6
作者：
Kharitonenkov, Alexei;Dunbar, James D.;Shanafelt, Armen B.
通讯作者：
Shanafelt, Armen B.
影响因子：
5.3
作者：
Goetz, Regina;Beenken, Andrew;Mohammadi, Moosa
通讯作者：
Mohammadi, Moosa
DOI：
10.1073/pnas.96.20.11041
发表时间：
1999-09-28
影响因子：
11.1
作者：
Brown, MS;Goldstein, JL
通讯作者：
Goldstein, JL
影响因子：
29
作者：
Badman, Michael K.;Pissios, Pavlos;Maratos-Flier, Eleftheria
通讯作者：
Maratos-Flier, Eleftheria