Figure 1.

Pathophysiological mechanisms of NAFLD and some critical events counteracted by the compounds. Adipose tissue expansion, insulin resistance, and caloric surplus can lead to free fatty acid accumulation in the liver, which inhibits VLDL synthesis, and thus increases the TG intrahepatic pool. These events, along with impaired with β-oxidation, promote steatosis. Lipotoxic species can then cause oxidative stress, inflammation, and fibrosis. The activation of hepatic stellate cells marks the promotion of NASH fibrosis. Nonhepatic players can also contribute directly or indirectly to NASH progression. Changes in gut microbiota composition can yield toxic microbiota products, or even form a leaky gut to release LPS or bacteria, all of which could contribute to hepatic inflammation. The compounds’ beneficial effects on NAFLD can be attributed to counteracting these critical pathological events and other nonhepatic players. Abbreviations: DAG, diacylglycerol; ECM, extracellular matrix; FFA, free fatty acids; IL-6, interleukin-6; IL-8, interleukin-8; IR, insulin resistance; IGF-1, insulin-like growth factor 1; LPS, lipopolysaccharides; PDGF, platelet-derived growth factor; TLR, toll-like receptor; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis—alpha; VLDL, very-low-density lipoprotein.