2024-03-28T19:07:18Zhttp://buleria.unileon.es/oai/requestoai:buleria.unileon.es:10612/56862023-06-08T11:54:50Zcom_10612_17col_10612_18
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
Porras, David
Nistal González, Maria Esther
Martínez Flórez, Susana
Pisonero-Vaquero, Sandra
Luis Olcoz, Luis
Jover Atienza, Ramiro
González Gallego, Javier
García Mediavilla, María Victoria
Sánchez-Campos, Sonia
Otros
Medicina. Salud
60 p.
Gut microbiota is involved in obesity, metabolic syndrome and the progression of
nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the
flavonoid quercetin may have the ability to modulate the intestinal microbiota
composition, suggesting a prebiotic capacity which highlights a great therapeutic
potential in NAFLD. The present study aims to investigate benefits of experimental
treatment with quercetin on gut microbial balance and related gut-liver axis activation in
a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were
challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks.
HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as
main hepatic histological finding. Increased accumulation of intrahepatic lipids was
associated with altered gene expression related to lipid metabolism, as a result of
deregulation of their major modulators. Quercetin supplementation decreased insulin
resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation
through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1
(CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition
was determined via 16S ribosomal RNA Illumina next-generation sequencing.
Metagenomic studies revealed HFD-dependent differences at phylum, class and genus
levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes
ratio and in Gram-negative bacteria, and a dramatically increased detection of
Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier
dysfunction and gut-liver axis alteration and subsequent inflammatory gene
overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-B signaling
pathway activation was associated with inflammasome initiation response and reticulum
stress pathway induction. Quercetin reverted gut microbiota imbalance and related
endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of
inflammasome response and reticulum stress pathway activation, leading to the
blockage of lipid metabolism gene expression deregulation. Our results support the
suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its
anti-inflammatory, antioxidant and prebiotic integrative response.Gut microbiota is involved in obesity, metabolic syndrome and the progression of
nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the
flavonoid quercetin may have the ability to modulate the intestinal microbiota
composition, suggesting a prebiotic capacity which highlights a great therapeutic
potential in NAFLD. The present study aims to investigate benefits of experimental
treatment with quercetin on gut microbial balance and related gut-liver axis activation in
a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were
challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks.
HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as
main hepatic histological finding. Increased accumulation of intrahepatic lipids was
associated with altered gene expression related to lipid metabolism, as a result of
deregulation of their major modulators. Quercetin supplementation decreased insulin
resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation
through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1
(CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition
was determined via 16S ribosomal RNA Illumina next-generation sequencing.
Metagenomic studies revealed HFD-dependent differences at phylum, class and genus
levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes
ratio and in Gram-negative bacteria, and a dramatically increased detection of
Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier
dysfunction and gut-liver axis alteration and subsequent inflammatory gene
overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-B signaling
pathway activation was associated with inflammasome initiation response and reticulum
stress pathway induction. Quercetin reverted gut microbiota imbalance and related
endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of
inflammasome response and reticulum stress pathway activation, leading to the
blockage of lipid metabolism gene expression deregulation. Our results support the
suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its
anti-inflammatory, antioxidant and prebiotic integrative response
2016-12-19
2016-12-19
2016-12-19
info:eu-repo/semantics/preprint
Free Radical Biology and Medicine, 2016,
http://hdl.handle.net/10612/5686
Elsevier