Preclinical studies have shown that in NAFLD models, FXR activation upregulates SREBP1c, IRS-1, and TNF-α while downregulating AMPK, exacerbating metabolic stress, dyslipidemia, and inflammatory/oxidative stress via downstream target regulation (Clifford et al., 2021). This evidence concerns the gene TNF and metabolic dysfunction-associated steatotic liver disease.