Diabetes Metab J.  2016 Feb;40(1):22-31. 10.4093/dmj.2016.40.1.22.

Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk

• Jin L
• Lin Z
• Xu A

• KMID: 2383311
• DOI: http://doi.org/10.4093/dmj.2016.40.1.22

Abstract

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.

Keyword

Adiponectin; Fibroblast growth factor 21; Hypercholesterolemia; Metabolic syndrome; Vascular diseases

MeSH Terms

Adipocytes
Adiponectin
Adipose Tissue
Animals
Apolipoproteins
Atherosclerosis*
Blood Vessels
Brain
Cholesterol
Energy Metabolism
Fibroblast Growth Factors*
Fibroblasts*
Foam Cells
Hepatocytes
Humans
Hypercholesterolemia
Insulin Resistance
Liver
Macrophages
Mice
Myocytes, Smooth Muscle
Obesity
Plaque, Atherosclerotic
Transcription Factors
Up-Regulation
Vascular Diseases
Adiponectin
Apolipoproteins
Cholesterol
Fibroblast Growth Factors
Transcription Factors

Figure

• 

  Fig. 1 Fibroblast growth factor 21 (FGF21) exerts its cardiovascular protective activitity via mediating the crosstalk between adipose tissue, brain, liver, and blood vessels. APN, adiponectin; Srebp-2, sterol regulatory element-binding protein 2.

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