Figure 1.

Schematic overview of metabolic and molecular pathways involved in the pathobiology of nonalcoholic steatohepatitis (NASH) and the effects of physical exercise thereon. Peripheral insulin resistance causes an increase in delivery of glucose and FFA to the liver. FA synthesis further increases FFA levels. When the mechanisms for FA storage as triglycerides (steatosis) and metabolism (β-oxidation) become overwhelmed, ROS production increases, resulting in mitochondrial and hepatocyte damage, DAMP release, and amplification of inflammation. Exercise affects these pathways at multiple levels, as indicated. Of note, multiple other pathways are involved in the pathogenesis of NASH. As the effects of exercise have not been investigated on these pathways, they are not included in this diagram. AMPK, AMP-activated protein kinase; DAMP, damage-associated molecular pattern; FA, fatty acid; FFA, free fatty acids; HCC, hepatocellular carcinoma; HMGB1, high-mobility group box-1; HSC, hepatic stellate cell; IR, insulin resistance; MMIF, macrophage migration inhibitory factor; mtDNA, mitochondrial DNA; mTOR, mammalian target of rapamycin; PPARα, peroxisome proliferator-activated receptor-α; ROS, reactive oxygen species; SREBP-1, sterol regulatory element-binding protein 1.