CD36 and DGAT2 facilitate the lipid-lowering effect of chitooligosaccharides via fatty acid intake and triglyceride synthesis signaling

Abstract

This study examined the impact of chitobiose (GlcN)₂ and chitotriose (GlcN)₃ on lipid accumulation modification and their inhibitory functionalities. (GlcN)₂ and (GlcN)₃ significantly inhibited the total cholesterol (TC), triglyceride (TG), and low-density lipid cholesterol (LDL-c) levels in the liver of the ob/ob^−/− mice fed a non-high-fat diet. This phenomenon was associated with a reduction in the mRNA and protein expression of TG synthesis and fatty acid uptake-related signaling, significantly affecting the cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). Furthermore, the CD36 and DGAT2 genes were overexpressed by constructing a plasmid and transfecting it into HepG2 cells, after which the phenotypic traits of lipid accumulation were assessed in vitro. Consequently, it was evident that (GlcN)₂ and (GlcN)₃ reduced the overexpression of these proteins and relieved cellular lipid accumulation. In conclusion, these results indicated that (GlcN)₂ and (GlcN)₃ acted positively against NAFLD while regulating steatosis in the non-high-fat diet NAFLD model. The potential NAFLD treatment strategies, such as targeting CD36 and DGAT2 signaling, could provide scientific insight into further applying food-derived ingredients to reduce the risk of high-fat metabolism.