High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We dem...High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Natural Science Foundation of China(32272364)Shanghai Engineering Research Center of food microbiology program(19DZ2281100).
文摘High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.
