Fig. 9.

Model of hepatic response to high-fat diet (HFD) and HFD plus physical activity via voluntary wheel running (VWR) in male and female mice. Male mice are more susceptible to HFD-induced hepatic steatosis than females. This is associated with increased hepatic mitochondrial H₂O₂ production and reduced mitochondrial coupling and efficiency. Females are protected from HFD-induced steatosis concomitant with low hepatic mitochondrial H₂O₂ production and increased coupling control. The addition of VWR in male mice drives their hepatic mitochondrial phenotype toward those of females by eliciting reduced steatosis and mitochondrial H₂O₂ production and increasing coupling.