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Leucine regulates lipid metabolism in adipose tissue through adipokine-mTOR-SIRT1 signaling pathway and bile acid—microbe axis in a finishing pig model

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Animal Nutrition 2024年第1期16卷 158-173页

作者： Yunju Yin Saiming Gong Mengmeng Han Jingzun Wang Hanjing Shi Xianji Jiang Liu Guo yehui duan Qiuping Guo Qinghua Chen Fengna Li Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessHunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production College of Animal Science and Technology Hunan Agricultural University College of Modern Agricultural Sciences University of Chinese Academy of Sciences College of Life Science and Engineering Northwest Minzu University

This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs.Twenty-four Duroc×Landrace×Large cross pigs with an average body weight of68.33±0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group (1 pig per replicate).The dietary treatments were as follows:control group (CON),0.25%Leu group and 0.50%Leu group.The experimental period was 42 d.The results showed as follows.(1) Compared with the CON,0.25%and 0.50%Leu increased (P<0.01) the average daily gain (ADG),while the average backfat thickness (ABT) and the ratio of feed intake to body weight gain (F:G ratio) were decreased (P<0.05).(2)In the 0.25%Leu group,the relative mRNA expression levels of sterol regulatory element binding protein-1c (SREBP1c),recombinant fatty acid transport protein 1 (FATP1),chemerin and peroxisome proliferatoractivated receptor γ (PPARγ) were decreased but the level of fatty acid binding protein 4 (FABP4) and fatty acid translocase (FAT/CD36) were increased in backfat tissue.In the 0.25%Leu group,the protein levels of p-Rictor,p-Raptor,p-eIF4E-binding protein 1 (p-4EBP1),p-silent mating type information regulator 2homolog 1 (p-SIRT1) and acetylation ribosome s6 protein kinase 1 (Ac—S6K1) were increased (P<0.05).(3) Compared to the CON,the diversity of gut microbiota in the 0.25%Leu group was increased.Principal component analysis showed that the relative abundance of Bacteroidetes,Lactobacillus and Desulfovibrio was higher in the 0.25%Leu group than the CON,but the relative abundance of Firmicutes,Treponema and Shigella was lower than in the CON (P<0.05).(4) Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid (alloLCA),isolithocholic acid (isoLCA),ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA),which correlate to various degrees with the above microorganisms.In conclusion,Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway,and S6K1 is a

关键词： Leu Lipid metabolism Gut microbiota Bile acid

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Science China Life Sciences 2024年

作者： Jiayi Yu Changbing Zheng Qiuping Guo Yulong Yin yehui duan Fengna Li CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production Institute of Subtropical Agriculture Chinese Academy of Sciences University of Chinese Academy of Sciences College of Animal Science and Technology Hunan Agricultural University

We previously demonstrated that lipopolysaccharide(LPS) injection-induced immune stress could impair muscle growth in weaned piglets, but the precise mechanisms behind this remain elusive. Here, we found that chronic immune stress induced by LPS resulted in a significant reduction of 36.86% in the total muscle mass of piglets at 5 d post-treatment compared with the control group. At 1 d,prior to muscle mass loss, multiple alterations were noted in response to LPS treatment. These included a reduction in the abundance of Bacteroidetes, an increase in serum concentrations of pro-inflammatory cytokines, compromised mitochondrial morphology, and an upregulation in the expression of dynamin-related protein 1(Drp1), a critical protein involved in mitochondrial fission. We highlight a strong negative correlation between Bacteroidetes abundance and the levels of serum pro-inflammatory cytokines, corroborated by in vivo intervention strategies in the musculature of both pig and mouse models. Mechanistically, the effects of Bacteroidetes on inflammation and muscle mass loss may involve the signaling pathway of the tauro-β-muricholic acid-fibroblast growth factor 15. Furthermore, the induction of overexpression of inflammatory cytokines, achieved without LPS treatment through oral administration of recombinant human IL-6(rhIL-6), led to increased levels of circulating cytokines, subsequently causing a decrease in muscle mass. Notably, pre-treatment with Mdivi-1, an inhibitor of Drp-1, markedly attenuated the LPS-induced elevation in reactive oxygen species levels and rescued the associated decline in muscle mass. Collectively, these data indicate that LPS-induced muscle mass loss was linked to the reduction of Bacteroidetes abundance, increased inflammation, and the disruption of mitochondrial morphology. These insights offer promising avenues for the identification of potential therapeutic targets aimed at mitigating muscle mass loss.

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Gut microbial profiles and the role in lipid metabolism in Shaziling pigs

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Animal Nutrition 2022年第2期9卷 345-356页

作者： Jie Ma yehui duan Rui Li Xiaoxiao Liang Tiejun Li Xingguo Huang Yulong Yin Jie Yin Animal Nutritional Genome and Germplasm InnovationResearch Center College of Animal Science and TechnologyHunan Agricultural UniversityChangsha410128China Institute of Subtropical Agriculture Chinese Academy of SciencesChangsha410125China Henan Ground Biological Science&Technology Co. Ltd.China

Shaziling pig,a Chinese indigenous breed,has been classified as a fatty pig model.However,the gut microbial development and role in lipid metabolism in Shaziling pigs has been rarely reported.Here,we compared the lipid metabolic and microbial profiles at 30,60,90,150,210,and 300 d of age between Shaziling and Yorkshire pigs.Predictably,there were marked differences in the liver lipids(i.e.,cholesterol,glucose,and low-density lipoprotein)and the lipid related expressions(i.e.,SREBP1/2,LXRa/b,DGAT1/2,and FABP1-3)between Shaziling and Yorkshire pigs.Bacteria sequencing in the ileal digesta and mucosa showed that Shaziling pigs had a higher a-diversity and higher abundances of probiotics,such as Lactobacillus johnsonii,Lactobacillus amylovorus,and Clostridium butyricum.Thirty-five differentiated metabolites were further identified in the mucosa between Shaziling and Yorkshire pigs,which were enriched in the carbohydrate,protein,glucose and amino acid metabolism and bile acid biosynthesis.Furthermore,7 differentiated microbial species were markedly correlated with metabolites,indicating the role of gut microbiota in the host metabolism.Next,the role of differentiated L.johnsonii in lipid metabolism was validated in Duroc×Landrace×Yorkshire(DLY)pigs and the results showed that L.johnsonii mono-colonization promoted lipid deposition and metabolism by altering gut microbiota(i.e.,Megasphaera elsdenii and L.johnsonii)and DGAT1/DGAT2/CD36-PPARg gene expressions.In conclusion,Shaziling pigs exhibited different metabolic and microbial profiles compared with Yorkshire pigs,which might have contributed to the diverse metabolic phenotypes,and the significant enrichment of L.johnsonii in Shaziling pigs promoted lipid metabolism and obesity of DLY pigs,which provided a novel idea to improve the fat content of lean pigs.

关键词： Shaziling pig Gut microbiota Lipid metabolism Lactobacillus johnsonii Fatty acid

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Effectiveness and safety evaluation of graded levels of N-carbamylglutamate in growing-finishing pigs

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Animal Nutrition 2022年第3期10卷 412-418页

作者： Chunping Wang Lijun Shang Qiuping Guo yehui duan Mengmeng Han Fengna Li Yulong Yin Shiyan Qiao State Key Laboratory of Animal Nutrition Ministry of Agriculture Feed Industry CentreChina Agricultural UniversityBeijing 100193China Beijing Bio-feed Additives Key Laboratory Beijing 100193China Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesChangsha 100045China University of Chinese Academy of Sciences Beijing 100039China

The aim of this study was as follows:1)to investigate the effects of graded levels of N-carbamylglutamate(NCG)on performance,blood biochemical indexes,carcass traits and related indicators in growingfinishing pigs,and 2)to determine the optimal supplemental level.The toxicity of high-dose(much higher than recommended levels)NCG was assessed by routine blood tests and blood biochemical and histopathologic examinations of the heart,liver,spleen,lung,kidney and stomach.One hundred and forty-four growing-finishing pigs(DurocLarge WhiteLandrace,32.24±1.03 kg)were used in a 74-d experiment and each treatment was replicated 6 times with 4 pigs(2 barrows and 2 gilts)per replicate.The dietary treatments were a corn-soybean meal basal diet supplemented with 0%(control),0.05%,0.1%,0.15%,0.2%or 1%NCG.The first 5 groups were used to explore the optimal supplemental level of NCG,while the control,0.1%and 1%NCG groups were used to explore the safety of high-dose NCG.Compared with the normal control group,the final body weight and average daily gain tended to be higher in the 0.1%group(P=0.08),the lean percentage tended to be higher in the 0.05%group(P=0.07),the levels of free amino acids in the blood significantly increased in the 0.1%group(P<0.05),both 0.1%and 0.15%NCG supplementation increased the levels of nitric oxide(NO)in serum(P=0.07)and muscle growth-and lipid metabolism-related gene expression(P<0.05)and NCG supplementation improved C18:1N9C monounsaturated fatty acids(MUFA)in a dose-dependent manner(P=0.08).In addition,routine blood tests,blood biochemical indexes and histopathological examination revealed no abnormalities.Overall,increasing the levels of NCG did not linearly improve the above indicators;the 0.1%dose showed the best effect,and a high dose(1%)did not pose a toxicity risk.

关键词： N-carbamylglutamate Growth performance Meat quality Effectiveness Safety

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Profiles of muscular amino acids,fatty acids,and metabolites in Shaziling pigs of different ages and relation to meat quality

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Science China(Life Sciences) 2023年第6期66卷 1323-1339页

作者： yehui duan Changbing Zheng Jie Zheng Lu Ma Xinran Ma Yinzhao Zhong Xichen Zhao Fengna Li Qiuping Guo Yulong Yin CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha410125China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing100049China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai200241China

Pork meat is closely related to physicochemical alterations during growth and development,resulting in differences in nutritional value and meat flavor.This study aimed to evaluate the composition of amino acids,fatty acids,and metabolic profiles in the longissimus thoracis muscle(LM)of Shaziling pigs aged 30,90,150,210,and 300 days.The results showed that the predominant fatty acids identified in the LM of Shaziling pigs were C16:0,C16:1,C18:0,C18:1n9c,and C18:2n6c.An opposite correlation was observed for C18:2n6c and n6/n3 polyunsaturated fatty acids(P<0.05).Alanine,aspartate,glutamate,Dglutamine,and D-glutamate metabolism were the main metabolic pathways for the Shaziling pig meat flavor(P<0.05).Moreover,the correlation coefficients revealed that the contents of anserine,C16:0,C16:1,and C18:1n9c were positively correlated with intramuscular fat and/or p H24hand were negatively correlated with the values of L^(*)(lightness)and b^(*)(yellowness)(P<0.05).In conclusion,age greatly affected the meat quality of Shaziling pigs,and the contents of muscular anserine,C16:0,C16:1,and C18:1n9c might be promising indicators for better meat quality.

关键词： Shaziling pigs meat quality amino acids fatty acids metabolites

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Comparisons of carcass traits,meat quality,and serum metabolome between Shaziling and Yorkshire pigs

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Animal Nutrition 2022年第1期8卷 125-134页

作者： Bo Song Changbing Zheng Jie Zheng Shiyu Zhang Yinzhao Zhong Qiuping Guo Fengna Li Cimin Long Kang Xu yehui duan Yulong Yin CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha410125China University of Chinese Academy of Sciences Beijing100039China

This study aims to compare the meat quality of Shaziling and Yorkshire pigs and to find the potential indicator in serum for superior meat quality.Six Shaziling and Yorkshire pigs at 30,60,90,150,210,and 300 d of age were selected to examine carcass traits,meat quality,and serum metabolome.The results showed that the body weight,carcass length,and loin eye area of Shaziling pigs at 150,210,and 300 d of age were significantly lower than those of Yorkshire pigs(P<0.05).Shaziling pigs at 150 and 300 d of age had significantly lower backfat thickness than Yorkshire pigs(P<0.05).Compared with Yorkshire pigs,Shaziling pigs at all 6 ages had a lower lean percentage and a higher fat percentage(P<0.05).At 60,90,and 150 d of age,the post-mortem pH-decline,b*value(yellowness),and drip loss of Shaziling pigs were significantly lower than those of Yorkshire pigs(P<0.05).Moreover,at 150 d of age,Shaziling pigs had significantly higher a^(*)value(redness)and intramuscular fat(IMF)content than Yorkshire pigs(P<0.05).Correlation analysis between the top 40 metabolites and phenotypes indicated that L-carnitine had positive correlations with fat percentage,pH24h,and IMF content,but had negative correlations with lean percentage,L^(*)value(lightness),and b^(*)value(P<0.05).Serum L-carnitine content,fat percentage,pH24h,and IMF content all decreased first and then increased as the pigs grew,which verified the positive correlations between L-carnitine and these phenotypes.In conclusion,Shaziling pigs have a slower growth rate but a better meat quality than Yorkshire pigs.The meat quality of Shaziling pigs is the best from 150 to 210 d of age.This study suggests that a higher serum L-carnitine content is a promising indicator for better meat quality.

关键词： Shaziling pig Yorkshire pig Carcass trait Meat quality Serum metabolome

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Engineered Bacillus subtilis alleviates intestinal oxidative injury through Nrf2-Keap1 pathway in enterotoxigenic Escherichia coli(ETEC) K88-infected piglet

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第6期24卷 496-509页

作者： Chaoyue WEN Hong ZHANG Qiuping GUO yehui duan Sisi CHEN Mengmeng HAN Fengna LI Mingliang JIN Yizhen WANG Institute of Feed Science Key Laboratory of Animal Feed and Nutrition of Zhejiang ProvinceKey Laboratory of Molecular Animal NutritionMinistry of EducationKey Laboratory of Animal Nutrition and Feed Science in Eastern ChinaMinistry of AgricultureCollege of Animal SciencesZhejiang UniversityHangzhou 310058China Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process CAS Key Laboratory of Agro-Ecological Processes in Subtropical RegionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China College of Advanced Agricultural Science University of Chinese Academy of SciencesBejing 100039China

Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties.In this study,we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32(WB800-KR32)using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli(ETEC)K88 in weaned piglets.Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet.The feed of the control group(CON)was infused with normal sterilized saline;meanwhile,the ETEC,ETEC+WB800,and ETEC+WB800-KR32 groups were orally administered normal sterilized saline,5×10^(10)CFU(CFU:colony forming units)WB800,and 5×10^(10)CFU WB800-KR32,respectively,on Days 1-14 and all infused with ETEC K881×10^(10)CFU on Days 15-17.The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance,improved the mucosal activity of antioxidant enzyme(catalase(CAT),superoxide dismutase(SOD),and glutathione peroxidase(GPx))and decreased the content of malondialdehyde(MDA).More importantly,WB800-KR32 downregulated genes involved in antioxidant defense(GPx and SOD1).Interestingly,WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum.WB800-KR32 markedly changed the richness estimators(Ace and Chao)of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces.The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway,providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.

关键词： Engineered probiotics Intestine Oxidative injury Weaned piglets Nuclear factor-E2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)pathway

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Antioxidant mechanism of tea polyphenols and its impact on health benefits

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Animal Nutrition 2020年第2期6卷 115-123页

作者： Zhaoming Yan Yinzhao Zhong yehui duan Qinghua Chen Fengna Li College of Animal Science and Technology Hunan Agricultural UniversityChangsha 410128China Laboratory of Animal Nutritional Physiology and Metabolic Process Institute of Subtropical Agriculture Chinese Academy of SciencesKey Laboratory of Agro-ecological Processes in Subtropical RegionHunan Provincial Engineering Research Center for Healthy Livestock and Poultry ProductionScientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-CentralMinistry of AgricultureChangsha 410125China College of Animal Science South China Agricultural UniversityGuangzhou 510642China Hunan Co-Innovation Center of Animal Production Safety Hunan Collaborative Innovation Center for Utilization of Botanical Functional IngredientsChangsha 410128China

Tea trees have a long history of cultivation and utilization.People in many countries have the habit of drinking tea and choosing green tea,oolong tea,or black tea according to different regions and personal tastes.Tea polyphe nols are a general term for polyphenol co mpounds in tea,and has been shown to have good effects on antioxidant,anti-inflammatory,cancer prevention and regulation of lipid metabolism.Tea polyphenols have been widely used as antioxidants in disease treatment and animal husbandry,but their specific mechanism of action needs to be further clarified and revealed.This review focuses on the definition,classification,antioxidant activity and the regulation of signaling pathways of tea polyphenols.This paper also aims to examine the application of tea polyphenols in human and animal health,providing a scientific basis for this application in addition to proposing future directions for the development of this resource.

关键词： Tea polyphenols Antioxidant activities Animal production Signal transduction pathway

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A selectively suppressing amino acid transporter: Sodium-coupled neutral amino acid transporter 2 inhibits cell growth and mammalian target of rapamycin complex 1 pathway in skeletal muscle cells

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Animal Nutrition 2020年第4期6卷 513-520页

作者： Lingyu Zhang yehui duan Qiuping Guo Wenlong Wang Fengna Li Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionHunan Provincial Engineering Research Center for Healthy Livestock and Poultry ProductionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangshaHunan 410125China Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central Ministry of AgricultureChangshaHunan 410125China University of Chinese Academy of Sciences Beijing100039China Laboratory of Animal Nutrition and Human Health School of BiologyHunan Normal UniversityChangsha410018China

Sodium-coupled neutral amino acid transporter 2(SNAT2),also known as solute carrier family 38 member 2(SLC38 A2),is expressed in the skeletal muscle.Our research previously indicated that SNAT2 m RNA expression level in the skeletal muscle was modulated by genotype and dietary protein.The aim of this study was to investigate the key role of the amino acid transporter SNAT2 in muscle cell growth,differentiation,and related signaling pathways via SNAT2 suppression using the inhibitor a-methylaminoisobutyric acid(Me AIB).The results showed that SNAT2 suppression down-regulated both the m RNA and protein expression levels of SNAT2 in C2 C12 cells,inhibited cell viability and differentiation of the cell,and regulated the cell distribution in G0/G1 and S phases(P<0.05).Meanwhile,most of the intercellular amino acid content of the cells after Me AIB co-culturing was significantly lower(P<0.05).Furthermore,the m RNA expression levels of system L amino acid transporter 1(LAT1),silent information regulator 1,and peroxisome proliferator-activated receptor-gamma co-activator 1 alpha,as well as the protein expression levels of amino acid transporters LAT1 and vacuolar protein sorting 34,were all down-regulated.The phosphorylated protein expression levels of mammalian target of rapamycin(m TOR),regulatory-associated protein of m TOR,4 E binding protein 1,and ribosomal protein S6 kinase 1 after Me AIB treatment were also significantly down-regulated(P<0.05),which could contribute to the importance of SNAT2 in amino acid transportation and skeletal muscle cell sensing.In conclusion,SNAT2 suppression inhibited C2 C12 cell growth and differentiation,as well as the availability of free amino acids.Although the m TOR complex 1 signaling pathway was found to be involved,its response to different nutrients requires further study.

关键词： a-methylaminoisobutyric acid Sodium-coupled neutral amino acid transporter 2 suppression Cell growth Mammalian target of rapamycin Muscle cell

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Oxidative stress, nutritional antioxidants and beyond

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Science China(Life Sciences) 2020年第6期63卷 866-874页

作者： Qiuping Guo Fengna Li yehui duan Chaoyue Wen Wenlong Wang Lingyu Zhang Ruilin Huang Yulong Yin Laboratory of Animal Nutritional Physiology and Metabolic Process Institute of Subtropical AgricultureChinese Academy of SciencesKey Laboratory of Agro-ecological Processes in Subtropical RegionHunan Provincial Engineering Research Center for Healthy Livestock and Poultry ProductionScientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-CentralMinistry of AgricultureChangsha 410125China University of Chinese Academy of Sciences Beiing 100039China Hunan Co-Innovation Center of Animal Production Safety Hunan Collaborative Innovation Center for Utilization of Botanical Functional IngredientsChangsha 410128China Laboratory of Animal Nutrition and Human Health School of BiologyHunan Normal UniversityChangsha 410018China

Free radical-induced oxidative stress contributes to the development of metabolic syndromes(Mets), including overweight,hyperglycemia, insulin resistance and pro-inflammatory state. Most free radicals are generated from the mitochondrial electron transport chain;under physiological conditions, their levels are maintained by efficient antioxidant systems. A variety of transcription factors have been identified and characterized that control gene expression in response to oxidative stress status.Natural antioxidant compounds have been largely studied for their strong antioxidant capacities. This review discusses the recent progress in oxidative stress and mitochondrial dysfunction in Mets and highlights the anti-Mets, anti-oxidative, and antiinflammatory effect of polyphenols as potential nutritional therapy.

关键词： reactive oxygen species oxidative stress mitochondrial dysfunction signal transduction nutritional antioxidant polyphenols

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