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high-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

Science China(Life Sciences) 2024年第5期67卷 879-891页

作者： Nianyi Zeng Fan Wu Junqi Lu Xiang Li Shaomei Lin Lang Zhou Zhongwei Wang Guangyan Wu Qingfa Huang Daowen Zheng Jie Gao Shan Wu Xiaojiao Chen Muxuan Chen Fanguo Meng Haitao Shang Yan He Peng Chen Hong Wei Zhuang Li Hongwei Zhou Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Environmental Health Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhou 510515China Redox Medical Center for Public Health Soochow UniversitySuzhou 215301China Precision Medicine Institute The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic ***,the underlying mechanism remains *** the present study,by comparing HFD-and normal diet(ND)-treated mice,we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut *** sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions,as confirmed by the increased reactive oxygen species(ROS)levels in fecal microbiota incubation in vitro and in the lumen,which were detected using in vivo fluorescence *** microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT)into germ-free(GF)mice,downregulating the gut barrier tight ***,mono-colonizing GF mice with an Enterococcus strain excelled in ROS production,damaged the gut barrier,induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells,and exacerbated fatty liver,compared with other low-ROS-producing Enterococcus *** administration of recombinant high-stability-superoxide dismutase(SOD)significantly reduced intestinal ROS,protected the gut barrier,and improved fatty liver against the *** conclusion,our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

关键词： fatty liver disease gut microbiota gut barrier high-fat diet oxidative stress reactive oxygen species

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high-fat diet and oral infection induced type 2 diabetes and obesity development under different genetic backgrounds

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Animal Models and Experimental Medicine 2023年第2期6卷 131-145页

作者： Iqbal M.Lone Nadav Ben Nun Aya Ghnaim Arne S.Schaefer Yael Houri-Haddad Fuad A.Iraqi Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Periodontology and Synoptic Dentistry Institute for Dental Craniofacial SciencesCharite-University of MedicineBerlinGermany Department of Prosthodontics Dental SchoolThe Hebrew UniversityJerusalemIsrael

Background:Type 2 diabetes(T2D)is an adult-onset and obese form of diabetes caused by an interplay between genetic,epigenetic,and environmental ***,we have assessed a cohort of 11 genetically different collaborative cross(CC)mouse lines comprised of both sexes for T2D and obesity developments in response to oral infection and high-fat diet(HFD)***:Mice were fed with either the HFD or the standard chow diet(control group)for 12 weeks starting at the age of 8 *** week 5 of the experiment,half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria *** the 12-week experimental period,body weight(BW)was recorded biweekly,and intraperitoneal glucose tolerance tests were performed at weeks 6 and 12 of the experiment to evaluate the glucose tolerance status of ***:Statistical analysis has shown the significance of phenotypic variations between the CC lines,which have different genetic backgrounds and sex effects in different experimental *** heritability of the studied phenotypes was estimated and ranged between 0.45 and *** applied machine learning methods to make an early call for T2D and its *** results showed that classification with random forest could reach the highest accuracy classification(ACC=0.91)when all the attributes were ***:Using sex,diet,infection status,initial BW,and area under the curve(AUC)at week 6,we could classify the final phenotypes/outcomes at the end stage of the experiment(at 12 weeks).

关键词： collaborative cross genetic covariance heritability high-fat diet machine learning mouse model obesity type 2 diabetes

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Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet

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Food Science and Human Wellness 2024年第2期13卷 659-667页

作者： Lanlan Gui Shaokang Wang Jing Wang Wang Liao Zitong Chen Da Pan Hui Xia Guiju Sun Su Tian Department of Nutrition and Food Hygiene School of Public HealthSoutheast UniversityNanjing 210009China Nanjing Municipal Center for Disease Control and Prevention Nanjing 210003China Department of Nutrition and Food Hygiene School of Public HealthHebei Medical UniversityShijiazhuang 050017China

Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood *** leaves of *** contain multiple chemical components and have a long history of use in folk medicines and health *** purpose of this study was to explore the effects of forsythin extract from *** leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat *** extract in *** leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat *** results suggested that forsythin extract in *** leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.

关键词： Forsythin high-fat diet Intestinal microbiota Short-chain fatty acid(SCFA)

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Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling

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Journal of Integrative Medicine 2024年第1期22卷 83-92页

作者： Lu-lu Han Xin Zhang Hui Zhang Ting Li Yi-chen Zhao Ming-hui Tian Feng-lei Sun Bo Feng Department of Neurology Three The Fifth People’s Hospital of JinanJinan 250013Shandong ProvinceChina Department of Gastroenterology Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina The First Clinical Medical College Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina Department of Geriatrics the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital)Jinan 250014Shandong ProvinceChina Chinese Medicine Culture and Literature Research Institute Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina Department of General Medicine Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250014Shandong ProvinceChina Department of Traditional Chinese Medicine the Second People’s Hospital of Haibei PrefectureZangzu Autonomous Prefecture of Haibei810300Qinghai ProvinceChina

Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk *** promotion of white adipose tissue(WAT)browning has emerged as a promising ***,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity ***,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an *** and insulin metabolism were assessed via glucose and insulin tolerance *** size was determined using hematoxylin and eosin *** expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain *** cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical ***,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling *** AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte ***,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical *** 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited t

关键词： Obesity Alisol B 23-acetate Adipose tissue mTOR-SREBP1 high-fat diet

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Targeted microbiome metabolomics reveals flaxseed oil supplementation regulated the gut microbiota and farnesoid X receptor pathway in high-fat diet mice

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Food Science and Human Wellness 2023年第6期12卷 2324-2335页

作者： Chen Yang Zhenxia Xu Qingde Huang Xu Wang Fenghong Huang Qianchun Deng Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences Oil Crops and Lipids Process Technology National&Local Joint Engineering LaboratoryHubei Key Laboratory of Lipid Chemistry and NutritionKey Laboratory of Oilseeds ProcessingMinistry of Agriculture and Rural AffairsWuhan 430062China College of Animal Science and Technology Huazhong Agricultural UniversityWuhan 430070China Institute of Agro-Food Science and Technology Shandong Academy of Agricultural SciencesJinan 250100China

Flaxseed oil(FSO)rich in n-3 polyunsaturated fatty acids(PUFAs)can protect against obesity and insulin resistance,but the underlying mechanism is *** integrative multiomics of the microbiome and targeted metab olomics approach was performed to investigate the possible pathway for flaxseed oil supplementation on reducing serum total cholesterol,triglyceride and epididymal adipose in high-fat diet *** ameliorated the gut microbial dysbiosis by increasing the community diversity and the abundance of Clostridiales and *** effects were associated with the regulation of bile acid(BAs)in the *** reduced the concentrations of conjugated BAs,such as cholic acid,tauro-α-murocholic acid,and tauro-ursodesoxycholic acid in feces,which in turn inhibit the intestinal farnesoid X receptor(FXR)-fibroblast growth factor(FGF)15 signaling *** analysis revealed that FSO activated FXR in the liver and regulated downstream gene expression(SHP,SREBP-1c,and CPT-1a),which promoted lipolysis and inhibited *** results of this study suggest that FSO modulates serum lipid concentrations by regulating the gut microbiota,FXR-FGF15 signaling and BA metabolism.

关键词： Flaxseed oil high-fat diet Gut microbiota Bile acids metabolomics FXR signaling

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Chlorogenic Acid Maintains Glucose Homeostasis through Modulating the Expression of SGLT-1,GLUT-2,and PLG in Different Intestinal Segments of Sprague-Dawley Rats Fed a high-fat diet

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Biomedical and Environmental Sciences 2015年第12期28卷 894-903页

作者： PENG Bing Jie ZHU Qi ZHONG Ying Li XU Shi Hao WANG Zheng College of Bioscience and Biotechnology Hunan Agricultural University

Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose *** Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent *** m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain ***-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using *** At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 ***-dose CGA inhibited the HFD-induced elevation in Sglt-1 *** CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal *** An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose *** can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.

关键词： Chlorogenic acid high-fat diet Intestine Glucose homeostasis SGLT-1 GLUT-2 PLG GLP-1

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Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

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Asian Journal of Andrology 2012年第4期14卷 635-642页

作者： Ines Tomada Nuno Tomada Henrique Almeida Delminda Neves Department of Experimental Biology Faculty of MedicineUniversidade do Porto--Alameda ProfHernmai MonteiroPorto 4200-319Portugal Instituto de Biologia Molecular e Celular(IBMC) Universidade do Porto--Rua do Campo Alegre 823Porto 4150-180Portugal Department of Urology Centro Hospital S.JoaoEPE-Alameda ProfessorHernmani MonteiroPorto 4200-319Portugal

The purpose of the current study was to evaluate the effect of a high-fat （HF） diet, energy restriction and exercise on the expression of vascular endothelial growth factor （VEGF）, angiopoietin （Ang） I and 2, and their receptors in rat corpus cavernosum （CC）. Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays （VEGF, VEGF receptor （VEGFR） I and 2, Angl, Ang2 and Tie2） and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase （eNOS） and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol （HDL-c） levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.

关键词： angiopoietins corpus cavernosum endothelial dysfunction energy restriction exercise high-fat diet VEGF

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Selenium reduces hepatopancreas lipid accumulation of grass carp(Ctenopharyngodon idella)fed high-fat diet via lipophagy activation

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Animal Nutrition 2023年第4期15卷 126-136页

作者： Xiaotian Zhang Haibo Yu Xianfang Yan Pengju Li Chi Wang Cheng Zhang Hong Ji College of Animal Science and Technology Northwest A&F UniversityYangling 712100China

It has been reported that selenium(Se)can reduce hepatopancreas lipid accumulation induced by highfat ***,its mechanism is still *** study aims to investigate the specific mechanisms by which Se alleviates high-fat diet-induced lipid *** carp were fed control diet(4.8%lipid,Con),high-fat diet(8.8%lipid,HFD)or HFD supplemented with 0.3 mg/kg nano-Se(HSe0.3)for *** performance,Se deposition,lipid accumulation,hepatic ultrastructure,and gene and protein expression levels associated with autophagy were ***,oleic acid(OA)was used to incubate the grass carp hepatocytes(L8824)for 24 h,and then the L8824 were incubated with sodium selenite in presence or absence of an autophagy inhibitor for 24 h.L8824 was analyzed for triglyceride concentration,immunofluorescence,and gene and protein expression levels associated with *** found that dietary nano-Se improved the growth of fish fed HFD and also decreased hepatosomatic index and intraperitoneal fat ratio of fish fed HFD(P<0.05).HFD significantly increased hepatopancreas lipid accumulation and decreased autophagic activity(P<0.05).Treatment of grass carp fed HFD with nano-Se decreased lipid accumulation and restored hepatic autophagy(P<0.05).In vitro,Se(100μM sodium selenite)obviously activated autophagy in L8824 incubated with OA,and consequently reduced the lipid accumulation induced by OA(P<0.05).Furthermore,using pharmacological inhibition(chloroquine)of the autophagy greatly diminished the beneficial effects of Se on alleviating OA-induced lipid accumulation and increased the co-localization of lipid droplets with autophagosome(P<0.05),which indicated that Se increased autophagic *** conclusion,these results suggest that Se alleviates HFD-induced hepatopancreas lipid accumulation by activating lipophagy.

关键词： Grass carp Selenium high-fat diet Lipid metabolism Lipophagy

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Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

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Food Science and Human Wellness 2024年第3期13卷 1672-1684页

作者： Ling Zhang Wenyu Zou Yongyan Hu Honghua Wu Ying Gao Junqing Zhang Jia Zheng Department of Endocrinology Peking University First HospitalBeijing 100034China Laboratory Animal Facility Peking University First HospitalBeijing 100034China

Exercise training is critical for the early prevention and treatment of obesity and diabetes ***,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and *** showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia *** profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis *** conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose *** further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

关键词： high-fat diet Voluntary wheel running Gut microbiota Metabolomics Glucose metabolism

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dietary nano-selenium alleviated intestinal damage of juvenile grass carp(Ctenopharyngodon idella)induced by high-fat diet:Insight from intestinal morphology,tight junction,inflammation,anti-oxidization and intestinal microbiota

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Animal Nutrition 2022年第1期8卷 235-248页

作者： Sha Liu Haibo Yu Pengju Li Chi Wang Guohao Liu Xiaotian Zhang Cheng Zhang Meng Qi Hong Ji College of Animal Science and Technology Northwest A&F UniversityYangling712100China Key Laboratory of Se-enriched Products Development and Quality Control Ministry of Agriculture and Rural AffairsAnkang725000China

In recent years,high-fat diet(HFD)has been widely applied in aquaculture,which reduces the intestinal health of cultured *** current study evaluated the protective effects of nano-selenium(nano-Se)on intestinal health of juvenile grass carp(Ctenopharyngodon idella)fed with HFD.A total of 135 experimental fish were fed with a regular diet(Con),a HFD(HFD)and a HFD containing nano-Se at 0.6 mg/kg(HSe)for 10 *** results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp(Pdietary nano-Se normalized the intestinal microbiota imbalance of juvenile grass carp caused by the HFD through increasing the abundance of the beneficial bacteria,e.g.,***,dietary nano-Se increased the production of short chain fatty acids(SCFA)in the intestine,especially for butyric acid and caproic acid,which were negatively related to the increase of intestinal permeability and *** summary,supply of nano-Se(0.6 mg/kg)in HFD could effectively alleviate intestinal injury of juvenile grass carp by improving intestinal barrier function and reducing intestinal inflammation and oxidative *** positive effects may be due to the regulatio

关键词： Nano-Se high-fat diet Inflammation Intestinal microbiota Short chainfattyacid

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