Fig. 5

Proposed mechanism for quercetin action against hepatic steatosis in obese mice. Excess intake of nutrients, including overloaded FFAs in obese conditions, increases ROS production in the liver; the latter results from lipid peroxidation and cause mitochondrial damage. The mitochondrial damage in turn leads to a decrease of mitochondrial oxidative capacity, including β-oxidation and ATP production, resulting in triglyceride accumulation in the liver. Quercetin limits hepatic lipid accumulation by enhancing hepatic mitochondrial oxidative metabolic capacity. Quercetin increases the induction of HO-1 and its byproduct CO by the upregulated transcriptional regulator Nrf-2. CO, enhances the nuclear translocation of Nrf-1 and PGC-1α, and activates Tfam expression, all of which augments mitochondrial biogenesis. This leads to reduction of FFA-induced lipid peroxidation, mitochondrial damage and hepatic triglyceride accumulation by increasing mitochondrial oxidative capacity. The effects of quercetin on the induction of HO-1 were completely disrupted in HO-1 inhibitor and/or Nrf-2 deficiency, indicating that one of the mechanisms by which quercetin enhances mitochondrial oxidative metabolism is associated with HO-1 induction through Nrf-2 pathway