HFD-induced liver steatosis (i) was reduced by 32% by EPA, without changes in oxidative stress-related parameters and mild recovery of Nrf2 functioning affording antioxidation and (ii) was decreased by 42% by HT, concomitantly with total regain of the glutathione status diminished by HFD, 42% to 59% recovery of lipid peroxidation and protein oxidation enhanced by HFD, and regain of Nrf2 functioning, whereas (iii) combined EPA + HT supplementation elicited 74% reduction in liver steatosis, with total recovery of the antioxidant potential in a similar manner than HT.
HFD-fed mice exhibited (i) liver steatosis; (ii) inflammation; (iii) oxidative stress; and (iv) depletion of n-3 LCPUFAs, together with down-regulation of PPAR-α and Nrf2, and up-regulation of NF-κB.
In summary, DMY likely modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and the inflammatory response in the pathological progression of ALD.
Nrf2 activation inhibits LXRα activity and LXRα-dependent liver steatosis by competing with FXR for p300, causing FXR activation and FXR-mediated SHP induction.