Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels.

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Citations to this article as recorded by  

• Fibroblast Growth Factor–Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications
  Leigang Jin, Ranyao Yang, Leiluo Geng, Aimin Xu
  Annual Review of Pharmacology and Toxicology.2023; 63(1): 359.     CrossRef
• Efruxifermin, an investigational treatment for fibrotic or cirrhotic nonalcoholic steatohepatitis (NASH)
  Tobias Puengel, Frank Tacke
  Expert Opinion on Investigational Drugs.2023; 32(6): 451.     CrossRef
• The role of perivascular adipose tissue-secreted adipocytokines in cardiovascular disease
  Meichao Cai, Dongsheng Zhao, Xiao Han, Shuang Han, Wenxin Zhang, Zhennan Zang, Chenchen Gai, Rong Rong, Tian Gao
  Frontiers in Immunology.2023;[Epub]     CrossRef
• Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis
  Cong Liu, Milena Schönke, Enchen Zhou, Zhuang Li, Sander Kooijman, Mariëtte R Boon, Mikael Larsson, Kristina Wallenius, Niek Dekker, Louise Barlind, Xiao-Rong Peng, Yanan Wang, Patrick C N Rensen
  Cardiovascular Research.2022; 118(2): 489.     CrossRef
• Relationship between Serum FGF21 and vWF Expression and Carotid Atherosclerosis in Elderly Patients with Hypertension
  Jing Bian, Lairong Chen, Qin Li, Yunfeng Zhao, Delu Yin, Shanhong Sun, Bhagyaveni M.A
  Journal of Healthcare Engineering.2022; 2022: 1.     CrossRef
• Serum FGF21 Levels Predict the MACE in Patients With Myocardial Infarction After Coronary Artery Bypass Graft Surgery
  Wei Xie, Dan Li, Yaru Shi, Ning Yu, Yu Yan, Yingchao Zhang, Qiongli Yu, Yulin Li, Jie Du, Zhuofeng Lin, Fan Wu
  Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
• Adipokines, adiposity, and atherosclerosis
  Longhua Liu, Zunhan Shi, Xiaohui Ji, Wenqian Zhang, Jinwen Luan, Tarik Zahr, Li Qiang
  Cellular and Molecular Life Sciences.2022;[Epub]     CrossRef
• Current understanding and controversies on the clinical implications of fibroblast growth factor 21
  Yasaman Badakhshi, Tianru Jin
  Critical Reviews in Clinical Laboratory Sciences.2021; 58(5): 311.     CrossRef
• The potential role of plasma fibroblast growth factor 21 as a diagnostic biomarker for abdominal aortic aneurysm presence and development
  Ting Xie, Liangying Yin, Dan Guo, Zixin Zhang, Yuexin Chen, Bao Liu, Wei Wang, Yuehong Zheng
  Life Sciences.2021; 274: 119346.     CrossRef
• Ultrasound-assisted C3F8-filled PLGA nanobubbles for enhanced FGF21 delivery and improved prophylactic treatment of diabetic cardiomyopathy
  Jiameng Gao, Jingjing Liu, Zheying Meng, Yanming Li, Yuping Hong, Lirui Wang, Lan He, Bing Hu, Yuanyi Zheng, Tianliang Li, Daxiang Cui, E. Shen
  Acta Biomaterialia.2021; 130: 395.     CrossRef
• Effect of Fibroblast Growth Factor 21 on the Development of Atheromatous Plaque and Lipid Metabolic Profiles in an Atherosclerosis-Prone Mouse Model
  Hyo Jin Maeng, Gha Young Lee, Jae Hyun Bae, Soo Lim
  International Journal of Molecular Sciences.2020; 21(18): 6836.     CrossRef
• The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic
  Leiluo Geng, Karen S. L. Lam, Aimin Xu
  Nature Reviews Endocrinology.2020; 16(11): 654.     CrossRef
• Two-hundred-liter scale fermentation, purification of recombinant human fibroblast growth factor-21, and its anti-diabetic effects on ob/ob mice
  Qi Hui, Zhen Huang, Shucai Pang, Xuanxin Yang, Jinghang Li, Bingjie Yu, Lu Tang, Xiaokun Li, Xiaojie Wang
  Applied Microbiology and Biotechnology.2019; 103(2): 719.     CrossRef
• Fibroblast growth factor 21: A role in cardiometabolic disorders and cardiovascular risk prediction?
  Niki Katsiki, Christos Mantzoros
  Metabolism.2019; 93: iii.     CrossRef
• Heparin‐poloxamer hydrogel‐encapsulated rhFGF21 enhances wound healing in diabetic mice
  Huan Liu, Yeli Zhao, Yuchi Zou, Wenting Huang, Liyun Zhu, Fei Liu, Dongxue Wang, Kaiming Guo, Jian Hu, Jun Chen, Lixia Ye, Xiaokun Li, Li Lin
  The FASEB Journal.2019; 33(9): 9858.     CrossRef
• Fibroblast growth factor 21 association with subclinical atherosclerosis and arterial stiffness in type 2 diabetes
  Saeed Yafei, Fathy Elsewy, Eman Youssef, Mohammed Ayman, Mohamed El-Shafei
  Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2019; 13(1): 882.     CrossRef
• Myokines in metabolic homeostasis and diabetes
  Jürgen Eckel
  Diabetologia.2019; 62(9): 1523.     CrossRef
• Inhibition of vascular neointima hyperplasia by FGF21 associated with FGFR1/Syk/NLRP3 inflammasome pathway in diabetic mice
  Wei Wei, Xiao-Xue Li, Ming Xu
  Atherosclerosis.2019; 289: 132.     CrossRef
• LY2405319, an analog of fibroblast growth factor 21 ameliorates α-smooth muscle actin production through inhibition of the succinate—G-protein couple receptor 91 (GPR91) pathway in mice
  Cong Thuc Le, Giang Nguyen, So Young Park, Dae Hee Choi, Eun-Hee Cho, Partha Mukhopadhyay
  PLOS ONE.2018; 13(2): e0192146.     CrossRef
• Relationship of Selected Adipokines with Markers of Vascular Damage in Patients with Type 2 Diabetes
  Jaromíra Spurná, David Karásek, Veronika Kubíčková, Dominika Goldmannová, Ondřej Krystyník, Jan Schovánek, Josef Zadražil
  Metabolic Syndrome and Related Disorders.2018; 16(5): 246.     CrossRef
• Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease
  Yun Shen, Xueli Zhang, Yiting Xu, Qin Xiong, Zhigang Lu, Xiaojing Ma, Yuqian Bao, Weiping Jia
  Cardiology.2018; 139(4): 212.     CrossRef
• Relationship between Circulating FGF21 Concentrations and the Severity of Coronary Artery Damage in Subjects with Cardiovascular Disease
  Sung Don Park, Kwi-Hyun Bae, Yeon-Kyung Choi, Jae-Han Jeon, Jung Beom Seo, Namkyun Kim, Chang-Yeon Kim, Sung Woo Kim, Won Kee Lee, Jung Guk Kim, In-Kyu Lee, Jang Hoon Lee, Keun-Gyu Park
  Journal of Lipid and Atherosclerosis.2018; 7(1): 42.     CrossRef
• Fibroblast growth factor 21 regulates foam cells formation and inflammatory response in Ox-LDL-induced THP-1 macrophages
  Nan Wang, Jun-yan Li, Shuai Li, Xiao-chen Guo, Tong Wu, Wen-fei Wang, De-shan Li
  Biomedicine & Pharmacotherapy.2018; 108: 1825.     CrossRef
• Chip‐based high resolution tandem mass spectrometric determination of fibroblast growth factor—chondroitin sulfate disaccharides noncovalent interaction
  Adrian C. Robu, Laurentiu Popescu, Daniela G. Seidler, Alina D. Zamfir
  Journal of Mass Spectrometry.2018; 53(7): 624.     CrossRef
• Conditioned medium from contracting skeletal muscle cells reverses insulin resistance and dysfunction of endothelial cells
  Yihe Zhao, Nana Li, Zhu Li, Da Zhang, Liming Chen, Zhi Yao, Wenyan Niu
  Metabolism.2018; 82: 36.     CrossRef
• Dietary n-3 long-chain polyunsaturated fatty acids upregulate energy dissipating metabolic pathways conveying anti-obesogenic effects in mice
  Stefanie Worsch, Mathias Heikenwalder, Hans Hauner, Bernhard L. Bader
  Nutrition & Metabolism.2018;[Epub]     CrossRef
• Metabolic Values of Fibroblasts Growth Factor 21 in Patients with Coronary Artery Disease and Obesity
  L. M. Pasiyeshvili, K. V. Ivanova
  Ukraïnsʹkij žurnal medicini, bìologìï ta sportu.2018; 3(4): 110.     CrossRef
• FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process
  Antero Salminen, Anu Kauppinen, Kai Kaarniranta
  Journal of Molecular Medicine.2017; 95(2): 123.     CrossRef
• Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses
  Antero Salminen, Kai Kaarniranta, Anu Kauppinen
  Ageing Research Reviews.2017; 37: 79.     CrossRef
• Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death
  Yun Shen, Xueli Zhang, Xiaoping Pan, Yiting Xu, Qin Xiong, Zhigang Lu, Xiaojing Ma, Yuqian Bao, Weiping Jia
  Cardiovascular Diabetology.2017;[Epub]     CrossRef
• Fibroblast growth factor 21 – a key player in cardiovascular disorders?
  Monika Lenart-Lipińska, Dariusz Duma, Magdalena Hałabiś, Marcin Dziedzic, Janusz Solski
  Hormone Molecular Biology and Clinical Investigation.2017;[Epub]     CrossRef
• The role of fibroblast growth factor 21 in atherosclerosis
  John Kokkinos, Shudi Tang, Kerry-Anne Rye, Kwok Leung Ong
  Atherosclerosis.2017; 257: 259.     CrossRef