Hormonal
FGF21 analogs reduce hepatic steatosis and lipotoxicity in NASH by suppressing de novo lipogenesis and increasing mitochondrial fatty acid oxidation, independent of weight loss.
FGF21 analogs are emerging therapies that target the hormonal drivers of liver fat. They work by telling the liver to stop making new fat and burn existing fat, rather than just restricting calories. This addresses the root cause of NASH (steatosis) rather than just the scarring (fibrosis).
Administration of FGF21, FGF21 analogs or adenoviral delivery of FGF21 reduces hepatic steatosis in diverse rodent models of NAFLD and NASH... The reduction in liver fat results from pleiotropic actions of FGF21, particularly suppressing caloric burden in the liver, reducing de novo lipogenesis, and increasing fat oxidation in the liver.
Why this rating
Evidence is primarily from preclinical rodent and primate models; human clinical data is referenced but detailed efficacy metrics are not provided in this review.
Source
FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases
Erik J. Tillman et al. · Frontiers in Endocrinology · 2020
DOI 10.3389/fendo.2020.601290
More from this paper
- FGF21 analogs exert direct anti-inflammatory effects in NASH by suppressing pro-inflammatory cytokine expression (TNF-a, IL-6, IL-1b) and inhibiting immune cell infiltration into the liver.Moderate
- Endogenous FGF21 levels are elevated in NASH patients but are insufficient to ameliorate disease due to a 'FGF21-resistant state' caused by receptor downregulation and enzyme-mediated inactivation.Moderate
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