背景:黄精多糖可预防肥胖和NAFLD。然而,PS根茎水提物(PSRwe)对肥胖和肝脏脂质积累的潜在影响仍未被研究。
目的:阐明PSRwe对HFD诱导的肥胖和肝脏脂肪沉积的影响及其机制。
方法:56只雄性小鼠,八周大,分为七组:阳性,四剂PSRwe,型号,和控制。HFD喂养八周,然后隔日灌胃奥利司他和PSRwe,为期8周.包含多组学的综合分析,生理和组织病理学,并采用生化指标。
方法:体重(BW);肝脏,脂肪和李指数;TC,TG,LDL-C,HDL-C,AST,ALT,FFA,瘦素,和肝脏和血液中的脂联素;TNFα,IL-6和LPS在结肠,等离子体,和肝脏;H&E,检查脂肪和肝脏样品上的PAS和油红O染色。OGTT和ITT进行了肠道微生物组,微生物代谢组,结肠和肝脏转录组,血浆和肝脏代谢物进行了研究。
结果:PSRwe在7.5mg/kg的剂量下显示出与奥利司他相比,BW和肝脂肪沉积显著且一致的降低。PSRwe显著降低TC,TG,LDL-C,LEP,血液和肝脏中的FFA水平。PSRwe显着增强了益生菌的相对丰度,包括Akkermansiamuciniphila,双歧杆菌,罗伊氏乳杆菌,和代谢途径包括糖酵解和脂肪酸β-氧化。在PSRwe处理的小鼠中的70个上调的微生物代谢产物主要参与核苷酸和氨基酸代谢,而40减少主要与脂质代谢有关的代谢物。上调的结肠差异表达基因(DEGs)参与JAK-STAT/PI3K-Akt/FoxO信号通路,血清素能/胆碱能/谷氨酸能突触,而下调的DEGs主要集中在脂肪的吸收和转运上。肝脏DEGs的上调主要集中在脂肪酸氧化和代谢上。肝脏代谢显示了131种不同的代谢产物,其中肉碱和氧化脂质在PSRwe治疗的小鼠中显著增加。在等离子体中,58种上调的代谢物主要参与辅因子/维生素的代谢,而154种下调的代谢物参与脂肪酸的生物合成。综合多组学关联分析显示,肠道菌群与结肠/肝脏基因表达之间存在显著关联。并提示外源性和内源性甜菜碱可能是缓解HFD诱导症状的活性化合物。
结论:PSRwe通过增加有益细菌有效减轻HFD诱导的肥胖和肝脂肪变性,减少结肠脂肪的消化/吸收,增加肝脏脂质代谢,提高甜菜碱水平.
BACKGROUND: Polygonatum sibiricum polysaccharides protect against obesity and NAFLD. However, the potential effects of PS rhizome aqueous extracts (PSRwe) on adiposity and hepatic lipid accumulation remains unexplored.
OBJECTIVE: Elucidating the impact and underlying mechanism of PSRwe on HFD-induced obesity and liver fat depostition.
METHODS: 56 male mice, aged eight weeks, were divided into seven groups: Positive, four doses of PSRwe, Model, and Control. HFD was fed for eight weeks, followed by alternate-day gavage of orlistat and PSRwe for an additional eight-week period. Integrative analysis encompassing multiomics, physiological and histopathological, and biochemical indexes was employed.
METHODS: Body weight (BW); liver, fat and Lee\'s indexes; TC, TG, LDL-C, HDL-C, AST, ALT, FFA, leptin, and adiponectin in the liver and blood; TNFα, IL-6, and LPS in the colon, plasma, and liver; H&E, PAS and oil red O staining on adipose and liver samples were examined. OGTT and ITT were conducted The gut microbiome, microbial metabolome, colonic and liver transcriptome, plasma and liver metabolites were investigated.
RESULTS: PSRwe at the dosage of 7.5 mg/kg demonstrated significant and consistent reduction in BW and hepatic fat deposition than orlistat. PSRwe significantly decreased TC, TG, LDL-C, LEP, FFA levels in blood and liver. PSRwe significantly enhanced the relative abundance of probiotics including Akkermansia muciniphila, Bifidobacterium pseudolongum, Lactobacillus reuteri, and metabolic pathways including glycolysis and fatty acids β-oxidation. The 70 up-regulated microbial metabolites in PSRwe-treated mice mainly involved in nucleotides and amino acids metabolism, while 40 decreased metabolites primarily associated with lipid metabolism. The up-regulated colonic differentially expressed genes (DEGs) participate in JAK-STAT/PI3K-Akt/FoxO signaling pathway, serotonergic/cholinergic/glutamatergic synapses, while the down-regulated DEGs predominantly focused on fat absorption and transport. The up-regulated liver DEGs mainly concentrated on fatty acid oxidation and metabolism. Liver metabolisms revealed 131 differential metabolites, among which carnitine and oxidized lipids significantly increased in PSRwe-treated mice. In plasma, the 58 up-regulated metabolites mainly participate in co-factors/vitamins metabolism while 154 down-regulated ones in fatty acids biosynthesis. Comprehensive multiomics association analysis revealed significant associations between gut microbiota and colonic/liver gene expression, and suggested exogenous and endogenous
betaine may be active compound in alleviating HFD-induced symptoms.
CONCLUSIONS: PSRwe effectively mitigate HFD-induced obesity and hepatic steatosis by increasing beneficial bacteria, reducing colonic fat digestion/absorption, increasing hepatic lipid metabolism, and elevating
betaine levels.