Chitosan Oligosaccharide Ameliorates Nonalcoholic Fatty Liver Disease (NAFLD) in Diet-Induced Obese Mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids—especially triglycerides (TGs) and free fatty acids (FFAs)—were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD.

The Molecular and Mechanistic Insights Based on Gut–Liver Axis: Nutritional Target for Non-Alcoholic Fatty Liver Disease (NAFLD) Improvement

“…Moreover, a fructo-oligosaccharides supply reversed high-fat diet feeding-induced reduction in level of Bifidobacteria and increase in plasma endotoxin content in mice [108]. Evidence from integrated lipidome and gut microbiome uncovered that chitosan oligosaccharide serves to ameliorate hepatic injury, steatosis, and inflammation as well as to reinforce the intestinal barrier [109]. Also, this oligosaccharide induced a reduction in the cecal abundance of Mucispirillum and an elevation in the content of Coprococcus [109].…”

“…Evidence from integrated lipidome and gut microbiome uncovered that chitosan oligosaccharide serves to ameliorate hepatic injury, steatosis, and inflammation as well as to reinforce the intestinal barrier [109]. Also, this oligosaccharide induced a reduction in the cecal abundance of Mucispirillum and an elevation in the content of Coprococcus [109]. Besides, the contribution of oligosaccharides to bile acid secretion and bile acid pool kinetics has been demonstrated in various animal models [110][111][112].…”

Protective Properties of FOXO1 Inhibition in a Murine Model of Non-alcoholic Fatty Liver Disease Are Associated With Attenuation of ER Stress and Necroptosis

“…The incidence of NAFLD in western countries has reached 30%, which has seriously affected worldwide healthcare (Abdelmalek, 2016;Younossi et al, 2016;Fiorucci et al, 2018). NAFLD is characterized by excessive fat deposition in hepatocytes caused by other definite liver-damaging factors besides alcohol and can progress to non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma (Qian et al, 2019). Thus, the treatment of NAFLD is a focus of world health concerns.…”

Probiotics and Prebiotics as a Strategy for Non-Alcoholic Fatty Liver Disease, a Narrative Review

“…In pre-clinical studies, an improvement in blood lipids has been reported after probiotic and prebiotic treatments [51,61,67,68,73,74]. Reduction in TC due to single and combined probiotic treatment (Lactobacillus) has been linked to the activation of the transcription of genes belonging to the liver X receptors (LXR) axis, inducing TC reverse transport and augmenting the conversion of TC to bile acids [75].…”