In vitro, CVC inhibited CCL2-induced increases in hepatocyte fatty acid synthase (Fasn) and adipose differentiation-related protein (Adrp), whereas it augmented acyl-coenzyme A oxidase 1 (Acox-1), proliferator-activated receptor gamma co-activator alpha (Pgc1α) and uncoupling protein 2 expression, suggesting mechanisms for attenuated hepatocyte steatosis.
Also in mice, irinotecan treatment induced hepatic ACOX1 expression, ERK phosphorylation and inflammation, as well as impairment of autophagy and significant steatosis.
HFD + RM mice had 40% less hepatic steatosis (<i>P</i> < 0.05) and lower upregulation of PPAR-α (33%), ACOX1 (50%), NRF2 (39%), and HO-1 (68%) protein concentrations than did the HFD mice (<i>P</i> < 0.05).<b>Conclusions:</b> Our findings suggest that RM supplementation prevents the obese phenotype observed in HFD-fed mice by downregulating inflammatory cytokine expression and secretion and stimulating hepatic antioxidant and fatty acid oxidation markers.
Fatty acyl-coenzyme A oxidase 1 (ACOX1) knockout (ACOX1(-/-)) mice manifest hepatic metabolic derangements that lead to the development of steatohepatitis, hepatocellular regeneration, spontaneous peroxisome proliferation, and hepatocellular carcinomas.