Serological (Wang X. et al., 2016) and pathological tests indicated that mice developed liver steatosis that was exacerbated by Nrf2 deletion after 8 weeks of HFD feeding. In condition of mild damage in hepatocytes, ALT from the cytoplasm leaks out because the membrane permeability is enhanced. While in condition of severe damage in hepatocytes, AST from mitochondria leaks out due to the disruption of mitochondrial membrane. Compared to the HFD-WT mice, the increase of AST and the decrease of ALT in HFD-Nrf2-null mice indicated that Nrf2 deficiency enhanced the hepatocytes damage induced by HFD feeding. ALP leaks into blood from hepatocytes in condition of liver damage. Kidney is considered to be the major organ that produces GGT, but the GGT in serum primarily comes from the hepatobiliary system. In heavily injured hepatocytes, GGT existed in the smooth endoplasmic reticulum will leak out into blood. Thus, the increase of serum ALP and GGT levels induced by Nrf2 deletion in HFD fed groups also demonstrated that Nrf2 deficiency accelerated the HFD-induced liver damage. Moreover, the grown macrovesicular fat accumulation in HFD-Nrf2-null mice liver in comparison with the HFD-WT mice indicated that Nrf2 deficiency intensified the liver sensibility to HFD feeding.
