Konjac Glucomannan and Its Degradation Products Inhibit Intestinal Lipid Absorption by Regulating Gut Microbiota and the Production of Short-Chain Fatty Acids.

The effect of konjac glucomannan (KGM) on lipid absorption is related to the viscosity effect and hepatic lipid synthesis. However, the molecular mechanism of regulation of intestinal lipid absorption by KGM and its correlation with gut microbiota have not been studied. This study explored the effects of KGM and degradation products of KGM (DKGM) on intestinal lipid absorption and output in obese mice and their potential mechanisms. The results showed that KGM significantly reduces blood lipids and intestinal lipid accumulation compared to DKGM in obese mice. Moreover, KGM and DKGM downregulated intestinal HDAC3 and NFLI3 expression to suppress CD36, SREBP1, FABP1, and PPARα expression. Notably, KGM more effectively inhibited fatty acid uptake in extraintestinal tissues than DKGM. Importantly, KGM more effectively enhanced the intestinal barrier, altered microbe abundance associated with lipid absorption, and promoted SCFA production than DKGM. Correlation analysis found that KGM and DKGM inhibited intestinal lipid absorption, which were positively correlated with the abundance of , , etc. In conclusion, KGM more effectively inhibits intestinal lipid absorption and output in high-fat diet mice than DKGM, which is related to viscosity, intestinal HDAC3 activity, and differential remodeling of the microbiome. These findings provide insights into how microbe-dietary fiber interactions regulate the host energy balance.