RESUMEN
Chitobiose (COS2) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS2 can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS2 involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS2 administration modulated the ß-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob-/- mice. Moreover, the hypolipidemic effect of COS2 and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate ß-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS2 in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver-gut axis signaling.
RESUMEN
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.