RT info:eu-repo/semantics/preprint
T1 Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation
A1 Porras, David
A1 Nistal González, Maria Esther
A1 Martínez Flórez, Susana
A1 Pisonero-Vaquero, Sandra
A1 Luis Olcoz, Luis
A1 Jover Atienza, Ramiro
A1 González Gallego, Javier
A1 García Mediavilla, María Victoria
A1 Sánchez-Campos, Sonia
A2 Otros
K1 Medicina. Salud
K1 CYP2E1
K1 Dysbiosis
K1 Intestinal microbiota
K1 Quercetin
AB Gut microbiota is involved in obesity, metabolic syndrome and the progression ofnonalcoholic fatty liver disease (NAFLD). It has been recently suggested that theflavonoid quercetin may have the ability to modulate the intestinal microbiotacomposition, suggesting a prebiotic capacity which highlights a great therapeuticpotential in NAFLD. The present study aims to investigate benefits of experimentaltreatment with quercetin on gut microbial balance and related gut-liver axis activation ina nutritional animal model of NAFLD associated to obesity. C57BL/6J mice werechallenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks.HFD induced obesity, metabolic syndrome and the development of hepatic steatosis asmain hepatic histological finding. Increased accumulation of intrahepatic lipids wasassociated with altered gene expression related to lipid metabolism, as a result ofderegulation of their major modulators. Quercetin supplementation decreased insulinresistance and NAFLD activity score, by reducing the intrahepatic lipid accumulationthrough its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1(CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota compositionwas determined via 16S ribosomal RNA Illumina next-generation sequencing.Metagenomic studies revealed HFD-dependent differences at phylum, class and genuslevels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetesratio and in Gram-negative bacteria, and a dramatically increased detection ofHelicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrierdysfunction and gut-liver axis alteration and subsequent inflammatory geneoverexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-B signalingpathway activation was associated with inflammasome initiation response and reticulumstress pathway induction. Quercetin reverted gut microbiota imbalance and relatedendotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition ofinflammasome response and reticulum stress pathway activation, leading to theblockage of lipid metabolism gene expression deregulation. Our results support thesuitability of quercetin as a therapeutic approach for obesity-associated NAFLD via itsanti-inflammatory, antioxidant and prebiotic integrative response.Gut microbiota is involved in obesity, metabolic syndrome and the progression ofnonalcoholic fatty liver disease (NAFLD). It has been recently suggested that theflavonoid quercetin may have the ability to modulate the intestinal microbiotacomposition, suggesting a prebiotic capacity which highlights a great therapeuticpotential in NAFLD. The present study aims to investigate benefits of experimentaltreatment with quercetin on gut microbial balance and related gut-liver axis activation ina nutritional animal model of NAFLD associated to obesity. C57BL/6J mice werechallenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks.HFD induced obesity, metabolic syndrome and the development of hepatic steatosis asmain hepatic histological finding. Increased accumulation of intrahepatic lipids wasassociated with altered gene expression related to lipid metabolism, as a result ofderegulation of their major modulators. Quercetin supplementation decreased insulinresistance and NAFLD activity score, by reducing the intrahepatic lipid accumulationthrough its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1(CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota compositionwas determined via 16S ribosomal RNA Illumina next-generation sequencing.Metagenomic studies revealed HFD-dependent differences at phylum, class and genuslevels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetesratio and in Gram-negative bacteria, and a dramatically increased detection ofHelicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrierdysfunction and gut-liver axis alteration and subsequent inflammatory geneoverexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-B signalingpathway activation was associated with inflammasome initiation response and reticulumstress pathway induction. Quercetin reverted gut microbiota imbalance and relatedendotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition ofinflammasome response and reticulum stress pathway activation, leading to theblockage of lipid metabolism gene expression deregulation. Our results support thesuitability of quercetin as a therapeutic approach for obesity-associated NAFLD via itsanti-inflammatory, antioxidant and prebiotic integrative response
PB Elsevier
YR 2016
FD 2016-12-19
LK http://hdl.handle.net/10612/5686
UL http://hdl.handle.net/10612/5686
NO Free Radical Biology and Medicine, 2016,
NO 60 p.
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 20-abr-2024