Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk
Diabetes & Metabolism Journal
;
: 22-31, 2016.
Article
in English
| WPRIM
| ID: wpr-90974
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Apolipoproteins
/
Transcription Factors
/
Vascular Diseases
/
Blood Vessels
/
Brain
/
Insulin Resistance
/
Up-Regulation
/
Adipose Tissue
/
Cholesterol
/
Adipocytes
Limits:
Animals
/
Humans
Language:
English
Journal:
Diabetes & Metabolism Journal
Year:
2016
Type:
Article
Similar
MEDLINE
...
LILACS
LIS