Research
Hormonal
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.
Your body naturally produces more FGF21 when you have fatty liver, but it doesn't work well enough to fix the problem. This is why specialized FGF21 analogs are being developed to bypass this resistance.
ModerateQualifiesMEDIUM confidence
However, this elevation of FGF21 observed in chronic, pathological metabolic states in humans does not appear sufficient to ameliorate disease. While decreased FGF21 receptor expression has been proposed to underlie this 'FGF21-resistant state,' the dramatic upregulation of fibroblast activation protein (FAP)... has been reported in liver and serum of patients with metabolic liver disease.
Why this rating
Based on observational data in human patients and preclinical models.
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
narrative_reviewCited 204×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- FGF21 analogs reduce hepatic steatosis and lipotoxicity in NASH by suppressing de novo lipogenesis and increasing mitochondrial fatty acid oxidation, independent of weight loss.Moderate
- 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
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