Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice

Circulation
Zhuofeng LinAimin Xu

Abstract

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. It acts as a key downstream target of both peroxisome proliferator-activated receptor α and γ, the agonists of which have been used for lipid lowering and insulin sensitization, respectively. However, the role of FGF21 in the cardiovascular system remains elusive. The roles of FGF21 in atherosclerosis were investigated by evaluating the impact of FGF21 deficiency and replenishment with recombinant FGF21 in apolipoprotein E(-/-) mice. FGF21 deficiency causes a marked exacerbation of atherosclerotic plaque formation and premature death in apolipoprotein E(-/-) mice, which is accompanied by hypoadiponectinemia and severe hypercholesterolemia. Replenishment of FGF21 protects against atherosclerosis in apolipoprotein E(-/-)mice via 2 independent mechanisms, inducing the adipocyte production of adiponectin, which in turn acts on the blood vessels to inhibit neointima formation and macrophage inflammation, and suppressing the hepatic expression of the transcription factor sterol regulatory element-binding protein-2, thereby leading to reduced cholesterol synthesis and attenuation of hypercholeste...Continue Reading

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Citations

Apr 9, 2016·International Journal of Cardiology·Yuan GuoDanyan Xu
Mar 20, 2016·Journal of Molecular Cell Biology·Xiaoyan HuiAimin Xu
Apr 20, 2016·Expert Review of Gastroenterology & Hepatology·Fa-Ling WuMing-Hua Zheng
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Jan 26, 2018·Journal of Atherosclerosis and Thrombosis·Yoshichika MiyazakiYukihiko Momiyama
Dec 6, 2018·Journal of Diabetes Investigation·Masato FuruhashiTetsuji Miura
Sep 25, 2017·Endocrine Reviews·Harald StaigerHans-Ulrich Häring
May 17, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·John E Mindur, Filip K Swirski
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Jan 4, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yeonsoo JoeHun Taeg Chung
Jul 18, 2020·Clinical Science·Lei ZhangXiao-Jing Zhang

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