Targeting FGF21 for the Treatment of Nonalcoholic Steatohepatitis. (March 2020)

• Record Type: Journal Article
• Authors: Zarei, Mohammad; Pizarro-Delgado, Javier; Barroso, Emma; Palomer, Xavier; Vázquez-Carrera, Manuel
• Is Part Of: Trends in pharmacological sciences. Volume 41:Number 3(2020)
• Page Start: 199
• Page End: 208
• Publication Date: 2020-03
• Subjects: FGF21 -- NASH -- fibrosis -- NAFLD -- steatosis -- triglyceride -- inflammation; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2019.12.005
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Nonalcoholic steatohepatitis (NASH), the severe stage of nonalcoholic fatty liver disease (NAFLD), is defined as the presence of hepatic steatosis with inflammation, hepatocyte injury, and different degrees of fibrosis. Although NASH affects 2–5% of the global population, no drug has been specifically approved to treat the disease. Fibroblast growth factor 21 (FGF21) and its analogs have emerged as a potential new therapeutic strategy for the treatment of NASH. In fact, FGF21 deficiency favors the development of steatosis, inflammation, hepatocyte damage, and fibrosis in the liver, whereas administration of FGF21 analogs ameliorates NASH by attenuating these processes. We review mechanistic insights into the beneficial and potential side effects of therapeutic approaches targeting FGF21 for the treatment of NASH. Highlights: No drug has yet been approved specifically for treating NASH, the necroinflammatory form of NAFLD which confers a higher risk of progression to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Targeting FGF21, a hormone with insulin-sensitizing and hepatoprotective properties, has emerged as an option for NASH therapy. FGF21 analogs have demonstrated efficacy in both animal models and humans with NASH, although some concerns have been raised about the safety of FGF21 analogs in humans. Strategies other than the use of FGF21 analogs that potentiate the effects of FGF21 and might be useful in the treatment of NASH are also being developed.