Hypolipidemic activity and mechanisms of carboxymethyl pachymaran: Impact of the degree of substitution

In this study, carboxymethyl pachymaran (CMP) with three different degrees of substitution were prepared and their hypolipidemic activities were investigated. CMP2 with a substitution degree of 0.791 had different molecular weight and surface smoothness textural profile than CMP1 (0.756) and CMP2 (0.871). All CMPs could reduce 0.5 mM oleic acid-induced lipid accumulation in HepG2 cells, however, CMP2 exhibited a stronger activity than that of CMP1 and CMP3 in lowering lipid and oxidative stress levels. The results demonstrated that CMP2 can reduce lipid levels , serum inflammatory factors and improve liver enzymes in mice. Moreover, the gut microbiota composition was balance and the levels of healthy beneficial short-chain fatty acids were increased treated by CMP2. RT-qPCR analysis demonstrated that CMP2 regulated hepatic and biliary cholesterol efflux by up-regulating the expression levels of LDLR, PPARα, and ABCA1 , while down-regulating the expression levels of SREBP-2. CMP2 effectively inhibited lipid accumulation in hepatocytes and attenuates inflammatory injury by a dual regulatory mechanism. Our results revealed potential to develop hypolipidemic functional foods with CMP2.