Cong Liu, MSc

Effects of FGF21 on cholesterol metabolism and atherosclerosis development in APOE*3-Leiden.CETP mice

Cardiovascular disease (CVD), mainly caused by atherosclerosis, is the leading cause of death worldwide.  Brown adipose tissue  (BAT) activation is a promising strategy to reduce atherosclerosis and its risk factors, including dyslipidemia, obesity and diabetes. Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects on lipid and lipoprotein metabolism, was shown to modulate BAT activity.  In mice and humans, FGF21 treatment reduces plasma fatty acid and triglyceride (TG) levels by accelerating TG-rich lipoprotein catabolism in white and brown adipose tissue. In humans, FGF21 also decreases plasma total and LDL-cholesterol, and increases HDL-cholesterol. However, the mechanisms underlying the effect of FGF21 on cholesterol metabolism, and the consequence of such modulation of cholesterol metabolism for atherosclerosis development, still needed to be investigated. Therefore, we aim to investigate the mechanisms by which FGF21 improves cholesterol metabolism and unravel its effect on atherosclerosis development by using APOE*3-Leiden.CETP mice, a well-established human-like model for studies on (V)LDL and HDL metabolism, aiming at providing further preclinical evidence for developing FGF21 as a therapeutic strategy for the treatment of cardiovascular disease.