Multiomics reveals the ameliorating effect and underlying mechanism of polygonatum sibiricum rhizome water extract on HFD-induced mouse obesity

Abstract

Background Polysaccharides and ethanol extract from Polygonatum sibiricum rhizome were reported to improve high-fat diet (HFD)-fed mouse obesity. However, the effect and potential mechanism of Polygonatum sibiricum rhizome water extract (PSRwe) on HFD-induced obesity mice remains unclear. The present study was sought to comprehensively elucidate that. An obese mouse model was established by feeding HFD and PSRwe were intragastrically administered once a day for 40 days. Changes in body weight, gut microbiota and their metabolites, plasma and liver metabolomics, colonic and liver transcriptomics were explored. The compounds in PSRwe were also examined.Results Body weight was significantly reduced after two weeks of PSRwe administration. Meanwhile, PSRwe treatment has significantly recovered the richness and diversity of gut microbiota in HFD-caused obesity mice. Specifically, beneficial species including Akkermansia muciniphila and functional pathways including fatty acids biosythesis and elongation, pentose phosphate pathway, glycolysis and reductive TCA cycle were significantly enriched in PSRwe group compared with oebsity. RNA-seq revealed that the function of the up-regulated DEGs in liver of PSRwe mice were mainly concentrated on lipid and fatty acid oxidation and metabolism, while the down-regulated DEGs were mainly focused on sterols and sterol biosynthesis and metabolism. In colon, however, the function of up-regulated DEGs were primarily JAK-STAT/PI3K-Akt signaling pathway, regulation of GTPase activity, and response to cation while the down-regulated DEGs were centered on glycolysis, fructose/mannose/pyruvate metabolism, fat digestion and absorption, and PPAR signaling pathway. Metabolomics analysis indicated that betaine, an effective component from PSR water extracts, has showed higher levels in both liver and plasma of PSRwe-treated mice, indicating that it was significantly associated with obesity. In addition, correlation analysis showed that the significantly different species enriched in PSRwe group were negatively correlated with colonic DEGs related on PPAR signaling pathway, glycolysis etc. but positively correlated with JAK-STAT signaling pathway etc. Intriguingly, common metabolites in plasma and liver were negatively correlated with liver DEGs related on steroids and sterols biosynthesis and metabolism but positively correlated with fatty acid metabolism.Conclusions Collectively, our study demonstrated that PSRwe could significantly alleviate HFD-induced mouse obesity via either directly affect lipid metabolism through effective betaine or by changing gut microbiota and their metabolites to alter gene expression associated with fatty acid metabolism in liver and colon, suggesting PSRwe might be a promising therapeutic candidate for obesity in clinical.