Chitosan oligosaccharide attenuates hepatic steatosis in HepG2 cells via the activation of AMP‐activated protein kinase

Chitosan oligosaccharides (COSs), oligomers of decomposed chitosan possess many biological functions including immunomodulatory, antitumor, and antiinflammation. The aim of this study was to investigate the protective effects of COS against free fatty acid (FFA)-induced cellular hepatic steatosis and underlying mechanisms in HepG2 cells. Results showed that COS significantly reduced the lipid contents and elevated the activities of antioxidant enzymes including total-superoxide dismutase, glutathione peroxidase, and catalase in FFA-stimulated HepG2 cells. COS phosphorylated the acetyl-CoA carboxylase and reduced both mRNA and protein levels of lipogenesis markers including fatty acid synthase and sterol regulatory element-binding protein 1c. COS also significantly increased the expression levels of fatty acid oxidation-related factors including carnitine palmitoyltransferase 1A, acyl-coenzyme A oxidase 1, and peroxisome proliferators-activated receptor α. Besides, COS markedly phosphorylated AMP-activated protein kinase (AMPK). The inhibition of lipogenesis and the enhancement of fatty acid oxidation induced by COS were all blocked by AMPK antagonist (compound C), showing that the attenuation of hepatic steatosis by COS was dependent on AMPK activation. In conclusion, COS attenuated hepatic steatosis via suppressing lipid synthesis and enhancing fatty acid oxidation. AMPK was also involved in the alleviation of hepatic steatosis by COS. These results indicated that COS might be used as a potential ingredient to ameliorate nonalcoholic fatty liver disease. PRACTICAL APPLICATIONS: Nonalcoholic fatty liver disease (NAFLD) has been regarded as pathological fat deposition in the liver, which includes a range of pathologies, from steatosis to steatohepatitis, fibrosis, and cellular carcinoma. Our findings demonstrated that Chitosan oligosaccharides (COS) attenuated steatosis via improving lipid metabolism. COS suppressed lipogenesis and also enhanced fatty acid oxidation. Besides, the underlying molecular mechanism whereby COS elicited these beneficial effects has also been proved to be through the modulation of upstream protein kinase, AMP-activated protein kinase. This study provides new knowledge to support that COS might be used as a food supplement for the prevention of NAFLD.