scholarly journals Microbiome Determinants and Physiological Effects of the Benzoate-Hippurate Microbial-Host Co-Metabolic Pathway

2019 ◽  
Author(s):  
François Brial ◽  
Julien Chilloux ◽  
Trine Nielsen ◽  
Sara Vieira-Silva ◽  
Gwen Falony ◽  
...  
Keyword(s):  
Cell Mass ◽  
Saturated Fat ◽  
Metabolic Health ◽  
Protective Effects ◽  
Liver Inflammation ◽  
High Fat ◽  
Translational Study ◽  
Depth Analysis ◽  
Gene Richness

ABSTRACTObjectiveGut microbial products are involved in type 2 diabetes, obesity and insulin resistance. In particular, hippurate, a hepatic phase 2 conjugation product of microbial benzoate metabolism, has been associated with a healthy phenotype. This study aims to identify metagenomic determinants and test protective effects of hippurate.DesignWe profiled the urine metabolome by 1H Nuclear Magnetic Resonance (NMR) spectroscopy to derive associations with metagenomic sequences in 271 middle-aged Danish individuals to identify dietary patterns in which urine hippurate levels were associated with health benefits. We follow up with benzoate and hippurate infusion in mice to demonstrate causality on clinical phenotypes.ResultsIn-depth analysis identifies that the urine hippurate concentration is associated with microbial gene richness, microbial functional redundancy as well as functional modules for microbial benzoate biosynthetic pathways across several enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate, independently of gene richness, accounts for links with metabolic health that we previously associated with gene richness. We then demonstrate causality in vivo through chronic subcutaneous infusions of hippurate or benzoate (20 nmol/day) resulting in improved glycemic control in mice fed a high-fat diet. Hippurate improved insulin secretion through increased β-cell mass and reduced liver inflammation and fibrosis, whereas benzoate treatment resulted in liver inflammation.ConclusionOur translational study shows that the benzoate-hippurate pathway brings a range of metabolic improvements in the context of high-fat diets, highlighting the potential of hippurate as a mediator of metabolic health.

scholarly journals Human and preclinical studies of the host–gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323314
Author(s):  
François Brial ◽  
Julien Chilloux ◽  
Trine Nielsen ◽  
Sara Vieira-Silva ◽  
Gwen Falony ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Human Study ◽  
Experimental Studies ◽  
Saturated Fat ◽  
Metabolic Health ◽  
High Fat ◽  
Chronic Infusion ◽  
Gene Richness ◽  
Fat Diets ◽  
Study Participants

ObjectiveGut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health.DesignIn 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes.ResultsIn the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion.ConclusionOur human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.

Protective effects of phyllanthin, a lignan from Phyllanthus amarus, against progression of high fat diet induced metabolic disturbances in mice

RSC Advances ◽  
2016 ◽  
Vol 6 (63) ◽  
pp. 58343-58353 ◽  
Author(s):  
Sneha Jagtap ◽  
Pragyanshu Khare ◽  
Priyanka Mangal ◽  
Kanthi Kiran Kondepudi ◽  
Mahendra Bishnoi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Peroxidation ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Phyllanthus Amarus ◽  
Protective Effects ◽  
Liver Inflammation ◽  
High Fat ◽  
Metabolic Disturbances ◽  
Induced Changes

Phyllanthin delayed the progression of high fat diet induced changes affecting lipid and glucose metabolism such as adiposity, hypertriglyceridemia, fatty liver, inflammation, lipid peroxidation and insulin resistance.

scholarly journals Protective Effects of the MushroomLactarius deterrimusExtract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mirjana Mihailović ◽  
Jelena Arambašić Јovanović ◽  
Aleksandra Uskoković ◽  
Nevena Grdović ◽  
Svetlana Dinić ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Islets ◽  
Diabetes Management ◽  
Therapeutic Potential ◽  
Cell Mass ◽  
Diabetic Rats ◽  
Nuclear Antigen ◽  
Protective Effects ◽  
Systemic Oxidative Stress

The aim of this study was to assess thein vivoeffects of the extract of the medicinal mushroom,Lactarius deterrimus, when administered (60 mg/kg, i.p.) daily for four weeks to streptozotocin- (STZ-) induced diabetic rats. Diabetic rats treated with theL. deterrimusextract displayed several improved biochemical parameters in the circulation: reduced hyperglycemia, lower triglyceride concentration and reduced glycated hemoglobin, glycated serum protein, and advanced glycation end product (AGE) levels. This treatment also adjusted the diabetes-induced redox imbalance. Thus, higher activities of the antioxidative enzymes, superoxide dismutase, and catalase in the circulation were accompanied by increased levels of free intracellular thiols and glutathionylated proteins after treatment with theL. deterrimusextract. In addition to a systemic antioxidant effect, the administration of the extract to diabetic rats also had a positive localized effect on pancreatic islets where it decreased AGE formation, and increased the expression of chemokine CXCL12 protein that mediates the restoration ofβ-cell population through the activation of the serine/threonine-specific Akt protein kinase prosurvival pathway. As a result, the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positiveβ-cells were increased. These results show that the ability of theL. deterrimusextract to alleviate oxidative stress and increaseβ-cell mass represents a therapeutic potential for diabetes management.

scholarly journals The mitochondrial calcium uniporter promotes arrhythmias caused by high-fat diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leroy C. Joseph ◽  
Michael V. Reyes ◽  
Edwin A. Homan ◽  
Blake Gowen ◽  
Uma Mahesh R. Avula ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Calcium Uptake ◽  
Saturated Fat ◽  
Calcium Handling ◽  
Mitochondrial Calcium ◽  
High Fat ◽  
Calcium Uniporter ◽  
Mitochondrial Calcium Uptake

AbstractObesity and diabetes increase the risk of arrhythmia and sudden cardiac death. However, the molecular mechanisms of arrhythmia caused by metabolic abnormalities are not well understood. We hypothesized that mitochondrial dysfunction caused by high fat diet (HFD) promotes ventricular arrhythmia. Based on our previous work showing that saturated fat causes calcium handling abnormalities in cardiomyocytes, we hypothesized that mitochondrial calcium uptake contributes to HFD-induced mitochondrial dysfunction and arrhythmic events. For experiments, we used mice with conditional cardiac-specific deletion of the mitochondrial calcium uniporter (Mcu), which is required for mitochondrial calcium uptake, and littermate controls. Mice were used for in vivo heart rhythm monitoring, perfused heart experiments, and isolated cardiomyocyte experiments. MCU KO mice are protected from HFD-induced long QT, inducible ventricular tachycardia, and abnormal ventricular repolarization. Abnormal repolarization may be due, at least in part, to a reduction in protein levels of voltage gated potassium channels. Furthermore, isolated cardiomyocytes from MCU KO mice exposed to saturated fat are protected from increased reactive oxygen species (ROS), mitochondrial dysfunction, and abnormal calcium handling. Activation of calmodulin-dependent protein kinase (CaMKII) corresponds with the increase in arrhythmias in vivo. Additional experiments showed that CaMKII inhibition protects cardiomyocytes from the mitochondrial dysfunction caused by saturated fat. Hearts from transgenic CaMKII inhibitor mice were protected from inducible ventricular tachycardia after HFD. These studies identify mitochondrial dysfunction caused by calcium overload as a key mechanism of arrhythmia during HFD. This work indicates that MCU and CaMKII could be therapeutic targets for arrhythmia caused by metabolic abnormalities.

scholarly journals Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

2020 ◽  
Vol 295 (37) ◽  
pp. 12975-12992 ◽  
Author(s):  
Xinlei Yao ◽  
Kun Li ◽  
Chen Liang ◽  
Zilong Zhou ◽  
Jiao Wang ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Mass ◽  
Therapeutic Use ◽  
Protective Effects ◽  
Β Cells ◽  
Β Cell ◽  
And Function ◽  
Pdx1 Expression

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet β-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to β-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve β-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in β-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of β-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet β-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring β-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet β-cells both in vitro and in vivo.

scholarly journals Palmatine ameliorates high fat diet induced impaired glucose tolerance

2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Xusheng Tian ◽  
Yukun Zhang ◽  
Han Li ◽  
Yunfeng Li ◽  
Ning Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Cell Apoptosis ◽  
High Fat Diet ◽  
Cell Mass ◽  
Mapk Signaling ◽  
High Fat ◽  
Β Cell

Abstract Background The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. Methods Male Sprague–Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. Results Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased β cell mass after the treatment of PAL. We further found out that PAL could alleviate the β cell apoptosis that accounts for β cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress β cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the β cell apoptosis and JNK signaling in vitro. Conclusion In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

Chronic, in vivo, PPARα activation prevents lipid overload in rat liver induced by high fat feeding

2009 ◽  
Vol 54 (1) ◽  
Author(s):  
M Wierzbicki ◽  
A Chabowski ◽  
M Żendzian-Piotrowska ◽  
E Harasim ◽  
J Górski
Keyword(s):  
Rat Liver ◽  
High Fat ◽  
Fat Feeding

Antioxidant Activity, Phenolic Content and Hematoprotective Effects of Cleome arabica Polyphenolic Leaf Extract

2019 ◽  
Author(s):  
C. Tigrine ◽  
A. Kameli
Keyword(s):  
Antioxidant Activity ◽  
Biological Effects ◽  
Reducing Power ◽  
Hematological Toxicity ◽  
Protective Effects ◽  
Ferrous Ions ◽  
Polyphenolic Extract ◽  
Cleome Arabica

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

2020 ◽  
Vol 27 (12) ◽  
pp. 1955-1996 ◽  
Author(s):  
Antonio Speciale ◽  
Antonella Saija ◽  
Romina Bashllari ◽  
Maria Sofia Molonia ◽  
Claudia Muscarà ◽  
...  
Keyword(s):  
Human Health ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Antioxidant Defenses ◽  
Noncommunicable Diseases ◽  
Protective Effects ◽  
Pathological Conditions ◽  
Chronic Pulmonary Diseases ◽  
Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

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