Main
very-low-density lipoprotein, SHTG, NASH, hypertriglyceridemia, TG
INSULIN RESISTANCE, HYPERTRIGLYCERIDEMIA, NONALCOHOLIC STEATOHEPATITIS (NASH), INSULIN SENSITIVITY
Severe hypertriglyceridemia (SHTG; ≥500 mg dlFibroblast growth factor 21 (FGF21) is an endogenous stress hormone that regulates lipid and glucose metabolism and energy expenditure. Preclinical data suggest that in the liver, FGF21 reduces fat via increased adenosine monophosphate-activated protein kinase (AMPK) signaling, which stimulates fatty acid oxidation and decreases de novo lipogenesis to mitigate new TG accumulation, and promotes TG secretion in the form of very-low-density lipoprotein (VLDL) to reduce existing fat stores. In adipose tissue, FGF21 improves insulin sensitivity and accelerates TG-rich lipoprotein turnover (for example, VLDL metabolism) as a result of activating brown adipose tissue and browning of white adipose tissue by inducing the expression of uncoupling protein 1 (refs. Pegozafermin is a glycopegylated recombinant analog of human FGF21 designed to have a longer half-life than native FGF21 while recapitulating the receptor activity profile of the native hormone. It is being developed for the treatment of SHTG and nonalcoholic steatohepatitis (NASH). Pegozafermin has previously demonstrated beneficial effects on serum lipids (TGs, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and HDL-C), insulin resistance, HbA1c, body weight and liver fat in patients with NASH