Non-alcoholic fatty liver disease (
NAFLD) includes a cluster of liver disorders ranging from simple
fatty liver to non-
alcoholic steatohepatitis (NASH) and
cirrhosis. Due to its liver and vascular complications,
NAFLD has become a public health problem with high morbidity and mortality. The pathogenesis of
NAFLD is considered a "multi-hit hypothesis" that involves lipotoxicity, oxidative stress, endoplasmic reticulum stress, a chronic inflammatory state and
mitochondrial dysfunction.
Fibroblast growth factor 21 (
FGF21) is a member of the
fibroblast growth factor family with multiple metabolic functions.
FGF21 directly regulates lipid metabolism and reduces hepatic
lipid accumulation in an
insulin-independent manner. Several studies have shown that
FGF21 can ameliorate the "multi-hits" in the pathogenesis of
NAFLD. The administration of
FGF21 reverses hepatic steatosis, counteracts
obesity and alleviates
insulin resistance in rodents and nonhuman primates. Using several strategies, we show that the reversal of simple
fatty liver and NASH is mediated by activation of the
FGF21 signaling pathway. In this review, we describe the molecular mechanisms involved in the onset and/or progression of
NAFLD, and review the current literature to highlight the therapeutic procedures associated with the
FGF21 signaling pathway for simple
fatty liver and NASH, which are the two most important types of
NAFLD.