Flavonoids and Related Compounds in Non-Alcoholic Fatty Liver Disease Therapy

P. 2991-3012Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is one of the most common chronic liver diseases, which may progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD is characterized by the accumulation of lipids in the liver arising from multiple factors: increased fatty acid uptake, increased de novo lipogenesis, reduced fatty acid oxidation and very low density lipoproteins (VLDL) secretion. Most therapeutic approaches for this disease are often directed at reducing body mass index and improving insulin resistance through lifestyle modifications, bariatric surgery and pharmacological treatments. Nevertheless, there is increasing evidence that the use of natural compounds, as polyphenols, exert multiple benefits on the disorders associated with NAFLD. These molecules seem to be able to regulate the expression of genes mainly involved in de novo lipogenesis and fatty acid oxidation, which contributes to their lipid-lowering effect in the liver. Their antioxidant, anti-inflammatory, antifibrogenic and antilipogenic properties seem to confer on them a great potential as strategy for preventing NAFLD progression. In this review, we summarized the effects of these compounds, especially flavonoids, and their mechanisms of action, that have been reported in several studies carried out in in vitro and in vivo models of NAFL

Dental emergency care in Spain during the state of alarm due to COVID-19 pandemic

The first state of alarm due to COVID-19 in Spain led to limit dental treatment exclusively to emergencies. The objective of the survey was to evaluate the amount and type of emergencies attended during this period, as well as to know how they were solve

Intestinal microbiota transplantation to germ-free mice in a in vivo model of nafld associated with a quercetin treatment

15 p.To select mice donors for intestinal microbiota transplantation based on its metabolic phenotype in response to a high fat diet (HFD) and quercetin treatment (Q). Intestinal microbiota. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Intestinal microbiota modulation in obesity-related non-alcoholic fatty liver disease

[EN] Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.SIThis work was supported by grants to JG-G and SS-C from Ministerio de Economía y Competitividad/FEDER (BFU2017- 87960-R) and Junta de Castilla y León (LE063U16 and GRS 1888/A/18). DP was supported by a fellowship from Junta de Castilla y León co-financed by the European Social Fund. EN was supported by Fundación de Investigación Sanitaria of León. MG-M was supported by CIBERehd contracts. CIBERehd is funded by the Instituto de Salud Carlos III, Spain

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

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 respons

Akkermansia spp. mediates protection from obesity-associated NAFLD development in germ free mice following intestinal microbiota transplantation from high fat diet and quercetin treated donors

1 p.Dysbiosis and gut-liver axis alteration have been pointed as important contributors to obesity and non-alcoholic fatty liver disease (NAFLD) development. Modulation of intestinal microbiota (IM) emerge as a promising therapeutic strategy for obesity-associated NAFLD. This study aims to determine the effect of IM transplantation and quercetin supplementation in a high fat diet (HFD)-based NAFLD model in germ free mice (GFm). Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Intestinal Microbiota Transplantation From HFD-fed and Quercetin Treated Donors Results in a Complex Metabolic Phenotype Transfer that Modulates Obesity-Related NAFLD in Germ Free Mice

2 p.Intestinal microbiota imbalance and related gut-liver axis activation have been identified as key mechanisms in nonalcoholic fatty liver disease (NAFLD) development. Modulation of intestinal microbiota, through administration of prebiotics or faecal microbiota transplantation, is a promising therapeutic approach for obesity associated diseases including NAFLD. The aim of the present study is to evaluate the benefits of gut microbiota transplantation from donors to germ free mice (GFm) following an experimental treatment with the flavonoid quercetin in a high fat diet (HFD)-based NAFLD model. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Metabolic Phenotype Transfer Through Gut Microbiota Transplantation from HFD-Fed and Quercetin Treated Donors Modulates Obesity-Related NAFLD in Germ-Free Mice

1 p.Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Strategies to modulate it, including faecal transplantation and administration of prebiotics as quercetin, are actively being examined. The present study aims to investigate benefits of experimental gut microbiota transfer from donors to germ-free mice (GFm) in a high-fat diet (HFD)-based NAFLD model. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Effect of exercise on gut microbiota and metabolic status modulation in an in vivo model of early obesity and NAFLD

1 p.Childhood obesity is one of the most serious public health concerns from this century, associated with metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) and gut microbiota alterations. Physical exercise improves obesity and NAFLD progression, modulating the gut microbial balance. We aim to investigate the effect of physical exercise on gut microbiota and the metabolic status of an in vivo model of early obesity, metabolic syndrome, and NAFLD. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Protective effect of quercetin treatment on HFD-induced intestinal dysbiosis and barrier dysfunction in an in vivo model of non-alcoholic fatty liver disease

1 p.Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Quercetin may have the ability to modulate the intestinal microbiota composition, suggesting therapeutic potential in NAFLD. The present study aims to investigate the beneficial effect of quercetin treatment on dysbiosis, intestinal barrier dysfunction and gut-liver axis alteration in high-fat diet (HFD)-fed mice. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S