Mechanism of blood fat-lowering effect by FGF21

Mechanism of blood fat-lowering effect by FGF21

FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, authors examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice.

Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT).

The research results, published in the journal Cell Metabolism, shows that a part of FGF21’s redistributing effect on fatty acids can be explained by the fat-splitting enzyme Lipoprotein lipase (LPL). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues.

In the study, the researchers also found that FGF21 changed the metabolic pattern in diabetic mice models and increased their metabolism of excess energy via brown adipose tissue.

In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT.