Page 10 - N. Metabolism and metabolic diseases
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[N. Metabolism and metabolic diseases-5]
Studies of the roles of NADPH oxidase 2 in Gut-liver axis-
induced non-alcoholic fatty liver disease
Ji Eun Kim¹, Hye Eun Lee¹, Yun Soo Bae¹
¹Life Sciences, Ewha Womans University, Seoul 03760, Korea
High fat diet (HFD)-induced endotoxemia and dysbiosis allows serum lipopolysaccharide (LPS) through increasing
permeability of intestinal microbial debris and stimulates a low-grade inflammation of various tissues. Recently,
NADPH oxidase 2 (Nox2)-mediated reactive oxygen species (ROS) are involved in hepatic inflammation. However,
no molecular connection between Nox2-mediated ROS and induction of endotoxemia and dysbiosis has been
reported. Here, we show Nox2 regulates hepatic injury through endotoxemia and dysbiosis. Level of serum LPS,
generation of steatosis, infiltration of F4/80 macrophage, and expression of α-SMA were increased in liver tissues
from WT with HFD, whereas the Nox2-deficient liver tissues failed to induce them, indicating that a low level of
serum LPS in Nox2 KO mice attenuates hepatic inflammation and fibrosis. Next, we investigated intestinal microbial
composition using RNA sequencing of feces from WT and Nox2 KO mice with HFD. Level of obesity-associated
microbe was increased in WT with HFD, whereas the microbe population was attenuated in Nox2 KO mice. Moreover,
populations of NASH-associated microbes were suppressed in Nox2 KO mice with HFD. Taken together, Nox2
regulates the progression of NASH through downregulation of NASH-associated microbes.
