Fig. 7.

Schematic diagram summarizing the effects of mitochondriotropic anti-oxidant AntiOxCIN₄supplementation in a WD-fed mice with NAFL phenotype. AntiOxCIN₄ supplementation reduced body weight gain of mice fed with a Western diet (WD) for 16 weeks. AntiOxCIN₄ also decreased liver weight with amelioration of hepatic damage markers (aspartate aminotransferase (AST)) and decreased steatosis with a reduction in the number/size of lipid droplets. These effects were shown to be partly attributed to increased fatty acid oxidation (FAO). AntiOxCIN₄ supplementation promoted a mitochondrial remodeling, which resulted in increased protein levels of Complex I subunits, prevention of WD modification on phosphatidylcholine/phosphatidylethanolamine (PC/PE) levels. Additionally, an induction of endogenous anti-oxidant defense system was also observed, with higher activity of mitochondrial superoxide dismutase (SOD). Furthermore, AntiOxCIN₄ prevented WD-induced impairment of autophagy quality control mechanism as shown by the avoidance of p62 accumulation and the maintenance of Beclin-1 and LC3-II protein levels. Moreover, AntiOxCIN₄ additionally increased lysosomal proteolytic activity as shown by higher lysosome-associated membrane glycoprotein 2 (LAMP2) and mannose-6-phosphate receptor (M6PR) levels. The amelioration of whole-body mouse parameters and especially, a healthier phenotype of hepatocytes support the use of AntiOxCIN₄ as a great potential agent for the prevention/treatment of NAFLD (details in Discussion).