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Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis

Cong Liu1,2, Milena Schönke1,2, Enchen Zhou1,2

  • 1Department of Medicine, Division of Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

Cardiovascular Research
|March 11, 2021
PubMed
Abstract

Insights

Fibroblast growth factor (FGF) 21 improves cholesterol levels by enhancing fat metabolism in adipose tissues. This reduces atherosclerosis severity and increases plaque stability, supporting FGF21 for cardiovascular disease treatment.

Area of Science:

  • Metabolic research
  • Cardiovascular science
  • Endocrinology

Background:

  • Fibroblast growth factor (FGF) 21 regulates energy metabolism and is studied for type 2 diabetes and NASH.
  • Its cardiovascular benefits, especially on lipoprotein metabolism and atherogenesis, are not fully understood.

Purpose of the Study:

  • To investigate the role of FGF21 in lipoprotein metabolism and atherosclerosis development.
  • To evaluate the effects of a recombinant FGF21 protein in a mouse model.

Main Methods:

  • Administered a half-life extended recombinant FGF21 protein to hypercholesterolemic APOE*3-Leiden.CETP mice.
  • Assessed changes in plasma lipids, adipose tissue activation (BAT and WAT browning), glucose tolerance, hepatic steatosis, and atherosclerotic lesion characteristics.

Main Results:

  • FGF21 significantly reduced plasma total and non-HDL cholesterol.
  • It promoted BAT activation and WAT browning, enhancing fatty acid uptake and lipoprotein remnant clearance.
  • Reduced body fat, improved glucose tolerance, ameliorated hepatic steatosis, decreased atherosclerotic lesion area, severity, and increased plaque stability.

Conclusions:

  • FGF21 improves hypercholesterolemia by accelerating triglyceride-rich lipoprotein turnover via BAT activation and WAT browning.
  • This leads to reduced atherosclerotic lesion severity and increased plaque stability.
  • These findings support the clinical use of FGF21 for atherosclerotic cardiovascular disease.
Keywords:
Adipose-liver axisAtherosclerotic cardiovascular diseaseBrown adipose tissueDyslipidaemiaLipoprotein metabolism

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