AIM:To examined the effects of a high-fat diet(HFD)on retinal pathological changes and dysfunction using peroxisome proliferator-activated receptor-alpha(PPARα)knockout mice.METHODS:For four months,C57BL/6J and PPAR...AIM:To examined the effects of a high-fat diet(HFD)on retinal pathological changes and dysfunction using peroxisome proliferator-activated receptor-alpha(PPARα)knockout mice.METHODS:For four months,C57BL/6J and PPARαknockout mice received either HFD or a standard diet(SD).A fluorometric method was used to determine the retinal triglycerides.The retinal malondialdehyde(MDA)content was measured.Hematoxylin-eosin was used to evaluate retinal pathological changes.Protein expression was analyzed by Western blot and immunofluorescence,while mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Electroretinogram was used to assess retinal function.RESULTS:HFD resulted in increased fatty acidβ-oxidation in the inner retina,particularly retinal ganglion cells(RGCs),as well as increased weight and accumulation of retinal triglyceride.Retinal fatty acid β-oxidation and triglyceride accumulation were affected by PPARα^(−/−)abnormalities.PPARαknockdown increased the infiltration and activation of inflammatory cells,as well as it upregulated the nuclear factor kappa B(NF-κB)signaling pathway and corresponding proinflammatory cytokine levels in the most retina subjected to the HFD.In the HFD mice,oxidative stress levels were elevated in the inner retina,particularly in the HFD PPARα^(−/−)mice.HFD-induced RGCs apoptosis initiation was exacerbated by PPARαdeficiency.Lastly,HFD feeding resulted in the lower amplitudes of scotopic a-wave,b-wave and photopic negative response(PhNR)wave,particularly in HFD PPARα^(−/−)mice.CONCLUSION:In HFD-fed mice retina,particularly in the inner retina,PPARα knockout increases lipid metabolic abnormalities,inflammatory responses,oxidative stress,apoptosis initiation and dysfunction.展开更多
High-fat diet(HFD)consumption induces gut microbiota dysbiosis and neuropsychiatric disorders,including anxiety.Previous research found that Tremella polysaccharide(TP)exhibited neuroprotective effects in vitro and in...High-fat diet(HFD)consumption induces gut microbiota dysbiosis and neuropsychiatric disorders,including anxiety.Previous research found that Tremella polysaccharide(TP)exhibited neuroprotective effects in vitro and in vivo.This study aimed to investigate the beneficial effects of TP on HFD-induced anxiety-like behaviors and elucidate the underlying mechanisms from the point view of the microbiota-gut-brain axis.Two groups of HFD-induced obese mice were orally gavaged with low dose(TPL,40 mg/kg)and high dose(TPH,400 mg/kg)of TP.A 12-week administration of TPH could significantly improve anxiety-like behaviors in HFD mice.In the hippocampus,microglia activation,the expression of blood-brain barrier(BBB)markers,and the levels of two neurotransmitters(serotonin and norepinephrine)were countered by TPH in mice consuming HFD.Furthermore,TPH improved the intestinal permeability and immune response of the enterocytes in HFD-fed mice.The gut microbiota dysbiosis induced by HFD was also rebalanced by TP treatments,especially in Proteobacteria and its lower taxa.The correlational analysis also suggested that shifts of some microbial genera were closely associated with body weight and the parameters of behavioral tests.Interestingly,fecal microbiota transplantation(FMT)results indicated that fecal microbiota from TPH-treated obese mice could prevent HFD-induced anxiety-like behaviors,suppressed microglia activation and intestinal permeability.In conclusion,the present study indicated that TP intake is a promising dietary intervention strategy to prevent HFD-induced anxiety via the microbiota-gut-brain axis.展开更多
The global rise in animal protein consumption has significantly amplified the demand for fodder.A comprehensive understanding of the diversity and characteristics of existing fodder resources is essential for balanced...The global rise in animal protein consumption has significantly amplified the demand for fodder.A comprehensive understanding of the diversity and characteristics of existing fodder resources is essential for balanced nutritional fodder production.This study investigates the diversity and composition of fodder plants and identifies key species for cattle in Zhaotong City,Yunnan,China,while documenting indigenous knowledge on their usage and selection criteria.Ethnobotanical surveys were conducted in 19 villages across seven townships with 140 informants.Data were collected through semi-structured interviews,free listing,and participatory observation,and analyzed using Relative Frequency Citation.A total of 125 taxa(including 106 wild and 19 cultivated)were reported.The most cited family is Poaceae(27 taxa,21.43%),followed by Asteraceae(17 taxa,13.49%),Fabaceae(14 taxa,11.11%),Polygonaceae(9 taxa,7.14%)and Lamiaceae(4 taxa,3.17%).The whole plant(66.04%)and herbaceous plants(84.80%)were the most used parts and life forms.The most cited species were Zea mays,Brassica rapa,Solanum tuberosum,Eragrostis nigra,and Artemisia dubia.Usage of diverse fodder resources reflects local wisdom in managing resource availability and achieving balanced nutrition while coping with environmental and climatic risks.Preferences for certain taxonomic groups are due to their quality as premier fodder resources.To promote integrated crop-livestock farming,we suggest further research into highly preferred fodder species,focusing on nutritional assessment,digestibility,meat quality impacts,and potential as antibiotic alternatives.Establishing germplasm and gene banks for fodder resources is also recommended.展开更多
The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur,which renders artificial feeding a crucial aspect.However,high-fat diets have always been asso...The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur,which renders artificial feeding a crucial aspect.However,high-fat diets have always been associated with a variety of digestive disorders.This study aimed to investigate the impact of high-fat diets on the gut microbiota and the mechanisms of gut damage in Nyctereutes procyonoides.16S rRNA sequencing demonstrated that high-fat diets caused diarrhea and intestinal damage through alterations in the gut microbiota:a decrease in the abundance of Firmicutes,an increase in the abundance of Proteobacteria and Actinobacteria,and an increase in the abundance of Enterococcaceae,Escherichia coli-Shigella,Clostridium and Lactobacillus.Subsequently,changes in metabolic path-ways,such as amino and fatty acid pathways,were identified by KEGG and COG enrichment analysis,and the TLR4/NF-κB/NLRP3 inflammatory signaling pathway was shown to be activated by high-fat diets.In addition,high-fat diets lead to the accumulation of ROS and MDA and reduce the activity of the antioxidant enzymes GSH-PX and SOD.C orrespondingly,the levels of proinflammatory cytokines(IL-6,IL-1βand TNF-α)were significantly increased,and the apoptosis and necrosis signaling pathways of colonic cells were detected,causing a dramatic decrease in the expression of intestinal tight junction proteins(Occludin,E-cadherin,ZO-1 and ZO-2).In conclusion,high-fat diets altered the structure of the Nyctereutes procyonoides gut microbiota community and led to colon damage.This study provides new insights into the intestinal health of Nyctereutes procyonoides.展开更多
Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,pa...Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.展开更多
Aflatoxin B_1(AFB_1)is a common contaminant in cereals of global concern,and long-term low-dose exposure can adversely affect human health.Here,we showed that populations with dietary patterns characterized by high-fa...Aflatoxin B_1(AFB_1)is a common contaminant in cereals of global concern,and long-term low-dose exposure can adversely affect human health.Here,we showed that populations with dietary patterns characterized by high-fat diet(HFD)might have an increased risk of exposure to high levels of AFB_1.Our data indicated that chronic exposure of AFB_1 induced“gut-liver axis”injury in mice under HFD and normal diet(ND)patterns.AFB_1 further aggravated hepatic and intestinal injury,and intestinal microbiota disruption in HFD mice.Bifidobacterium breve BAA-2849 intervention analysis showed that liver injury and lipid disorders caused by AFB_1 exposure were alleviated by regulating the proportions of different gut microbes.We demonstrated through a mice model that the populations with a dietary pattern of HFD might be more susceptible to AFB_1 exposure and adverse effects on the gut-liver axis,and the toxicity of AFB_1 exposure can be alleviated by regulating the gut microbiota.展开更多
Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,altho...Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,although the underlying mechanisms have yet to be determined.We examined the effects of 3ʹ-SL on glycolipid metabolism in mice fed a high-fat diet.Male C57BL/6J mice were divided into 6 groups:2 model control groups(normal and high-fat diets)and 4 intervention groups(Neu5Ac,and low,moderate,and high-dose 3ʹ-SL).After 8 weeks of continuous gavage intervention,mice in the 3ʹ-SL intervention groups had lower body weight and total fat content;reduced fasting blood glucose,triglycerides,low-density lipoproteins and oxidized-low-density lipoproteins;and increased high-density lipoproteins,but no dosage-dependent of 3ʹ-SL intervention was found,moderate-dose 3ʹ-SL intervention as optimal for further exploration.3ʹ-SL intervention could increase respiratory exchange ratio,energy expenditure,and amount of exercise performed.3ʹ-SL increased the colonic abundances of Akkermansia,Lactobacillus,and Bacteroides,and reduced those of Erysipelatoclostridium,Faecalibaculum,and Aldercreutzia.Changes were also observed in colonic metabolites,and liver gene transcript and metabolites,which were mainly enriched in bile secretion,taurine and hypotaurine metabolism,and insulin resistance.Additionally,3ʹ-SL was observed to regulate genes associated with physiological rhythms,including Clock,Per2,Cry1,and Bhihe41.Collectively,our findings indicate that 3ʹ-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets.Compared with Neu5Ac,3ʹ-SL intervention can more effectively ameliorate intestinal flora disorders,enhance bile acid circulation,increase tissue energy expenditure,and reduce lipid synthesis,thereby promoting lipid-lowering effects mediated via the gut-liver axis,and can also enhance energy metabolism and alleviate disorders of glucolipid metabolism by altering physiological rhythms in high fat-diet mice.展开更多
Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxa...Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.展开更多
Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-...Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-induced mice was investigated.Results showed that AVN B significantly inhibited weight gain and improved hepatic and serum lipid biochemical indices.Hepatic RNA-sequencing analysis suggested that AVN B significantly modulates fatty acid(FA)metabolism.Hepatic real-time qualitative polymerase chain reaction(RT-q PCR)and Western blot results indicated that AVN B could alleviate FA synthesis by activating the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)-sterol regulatory element binding protein-1c(SREBP1c)-fatty acid synthase(FAS),and increase FA oxidation by activating the AMPK/carnitine palmitoyltransferase 1A(CPT1A)and peroxisome proliferator-activated receptorα(PPARα).Additionally,AVN B had a regulating effect on ileum lipid metabolism by inhibiting intestinal cell differentiation and downregulating the expression levels of FA absorption-related protein and gene.Moreover,AVN B promoted the growth of beneficial bacteria and fungi such as Coriobacteriaceae_UCG-002,Parvibacter,Enterococcus,and Aspergillus,while decreasing the abundance of Roseburia,unclassified_f_Lachnospiraceae,Cladosporium,Eurotium,unclassified_f_Aspergillaceae and unclassified_f_Ceratocystidaceae.All these results provided new points of the lipid-lowing mechanism of AVNs and oats via the gut-liver axis.展开更多
It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function.The concept of multi-organ crosstalk coordinating disease progression has become the current research...It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function.The concept of multi-organ crosstalk coordinating disease progression has become the current research hot topic.However,there remains an urgent need to elucidate its specific mechanisms.This study aimed to explore the impact of a high-fat diet(HFD)on liver health and cognitive function,and to further uncover the regulatory effect of aerobic exercise by liver-specific activating transcription factor 3(Atf3)knockout(ATF3cKO)mice in a“liver-brain”axis mode.The 5-week-old C57BL/6 and ATF3cKO mice were fed with HFD for 32 weeks,and sequentially subjected to aerobic exercise intervention at the 20th week for another 12 consecutive weeks.Meanwhile,C57BL/6 mice were provided with a normal diet as the control group.The functional parameters of liver and brain of all mice were assessed.Cognitive capacity of all mice was assessed by the Morris water maze(MWM).Inflammatory factors in the serum and brain of mice were quantified using enzyme-linked immunosorbent assay(ELISA),and the expression of inflammasomes was detected by immunohistochemistry(IHC).Additionally,the activation of nuclear factor-κB(NF-κB)and phosphoinositide 3-kinase(PI3K)signal pathways was analyzed by Western blotting.In this study,HFD impaired hepatic and brain functions,while aerobic exercise and liver-specific Atf3 knockout suppressed inflammatory factors in the peripheral circulation through hepatoprotective mechanisms,thereby attenuating cerebral inflammation and preserving neurological integrity,as well as mitigating HFD-induced cognitive decline.展开更多
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 circulation.The leaves o...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 circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa 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 diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.展开更多
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 ...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 strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,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 HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,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 pathways.Results 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 size.Moreover,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 activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.展开更多
Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running o...Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,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 metabolites.It 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 genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In 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 intolerance.We 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.展开更多
BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therape...BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.METHODS To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with LGZG.The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests.Using a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic steatosis.It effectively controlled blood glucose and food intake while protecting islet cells.Metabolite analysis revealed significant differences between the HFD and HFDLGZG groups.LGZG intervention reduced branched-chain amino acid levels.Levels of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased significantly.IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by qRT-PCR.CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR.LGZG may activate S6K1 via metabolic pathways.These findings lay the groundwork for the potential of LGZG as an IR treatment.展开更多
BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migratio...BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migration of lipopolysaccharide(LPS)to other tissues.AIM To evaluate the chronic effects(at 10 and 16 wk)of a high-fat diet(HFD)(with 50%energy as fat)on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice.METHODS Forty adult male mice were divided into four nutritional groups,where the letters refer to the type of diet(control and HFD or HF)and the numbers refer to the period(in weeks)of diet administration:Control diet for 10 wk,HFD for 10 wk,control diet for 16 wk,and HFD for 16 wk.After sacrifice,biochemical,molecular,and stereological analyses were performed.RESULTS The HF groups were overweight,had gut dysbiosis,had a progressive decrease in occludin immunostaining,and had increased LPS concentrations.Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group,consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake.CONCLUSION Chronic HFD intake causes overweight,gut dysbiosis,and morphological and functional alterations of the intestinal barrier after 10 or 16 wk.Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.展开更多
Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an impo...Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.展开更多
Gut microbiota regulate the activation of adipose browning,which promote energy dissipation and combat diet-induced obesity.Pomegranate peel polyphenols(PPPs)have been shown to reduce obesity,regulate lipid metabolism...Gut microbiota regulate the activation of adipose browning,which promote energy dissipation and combat diet-induced obesity.Pomegranate peel polyphenols(PPPs)have been shown to reduce obesity,regulate lipid metabolism in adipose tissue,and modulate the composition of gut microbiota in animal fed high-fat diet(HFD).However,the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated.In current study,we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs.The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning,and change the fecal metabolomic profiles in respond to PPPs.Moreover,the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites,such as urolithin A,short-chain fatty acids(SCFAs),and bile acids(BAs),which were associated with activating adipose browning.Therefore,our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity.The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.展开更多
High-fat diet(HFD)promotes the imbalance of gut microbiota,contributing to the development of metabolic disorders.Pomegranate juice(PJ)and inulin,as dietary polyphenol and dietary fiber respectively,have been reported...High-fat diet(HFD)promotes the imbalance of gut microbiota,contributing to the development of metabolic disorders.Pomegranate juice(PJ)and inulin,as dietary polyphenol and dietary fiber respectively,have been reported to ameliorate diet-induced gut microbiota dysbiosis and metabolic disorders.However,the combined effect of PJ and inulin on HFD-induced metabolic disorders has not been elucidated.In current study,we found that the combination of PJ and inulin prevent HFD-induced obesity,dyslipidemia,and gut microbiota dysbiosis.Moreover,the fecal levels of short-chain fatty acids(SCFAs)produced by inulin were increased after inulin combined with PJ.The levels of pomegranate polyphenol metabolites produced by PJ were also increased after PJ combined with inulin,especially pharmacokinetic analysis showed that the presence of inulin enhance the absorption level of urolithin A.Fecal metabolomic analysis found that PJ combined with inulin alter the metabolic status compared with PJ.It was also showed that the levels of SCFAs and pomegranate polyphenol metabolites among groups were correlated with gut microbiota and metabolic disorders indicators.Our results suggested that PJ combined with inulin prevent HFD-induced metabolic disorders,which may be attributed to the promotion of mutual metabolic transformation and absorption of PJ and inulin by gut microbiota.展开更多
基金Supported by the Anhui Medical University Research Fund(No.2023xkj035)National Natural Science Foundation Incubation Program Project of the Second Affiliated Hospital of Anhui Medical University(No.2023GQFY05)the Key Research and Development Technology project of Anhui Province(No.2022j11020013).
文摘AIM:To examined the effects of a high-fat diet(HFD)on retinal pathological changes and dysfunction using peroxisome proliferator-activated receptor-alpha(PPARα)knockout mice.METHODS:For four months,C57BL/6J and PPARαknockout mice received either HFD or a standard diet(SD).A fluorometric method was used to determine the retinal triglycerides.The retinal malondialdehyde(MDA)content was measured.Hematoxylin-eosin was used to evaluate retinal pathological changes.Protein expression was analyzed by Western blot and immunofluorescence,while mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Electroretinogram was used to assess retinal function.RESULTS:HFD resulted in increased fatty acidβ-oxidation in the inner retina,particularly retinal ganglion cells(RGCs),as well as increased weight and accumulation of retinal triglyceride.Retinal fatty acid β-oxidation and triglyceride accumulation were affected by PPARα^(−/−)abnormalities.PPARαknockdown increased the infiltration and activation of inflammatory cells,as well as it upregulated the nuclear factor kappa B(NF-κB)signaling pathway and corresponding proinflammatory cytokine levels in the most retina subjected to the HFD.In the HFD mice,oxidative stress levels were elevated in the inner retina,particularly in the HFD PPARα^(−/−)mice.HFD-induced RGCs apoptosis initiation was exacerbated by PPARαdeficiency.Lastly,HFD feeding resulted in the lower amplitudes of scotopic a-wave,b-wave and photopic negative response(PhNR)wave,particularly in HFD PPARα^(−/−)mice.CONCLUSION:In HFD-fed mice retina,particularly in the inner retina,PPARα knockout increases lipid metabolic abnormalities,inflammatory responses,oxidative stress,apoptosis initiation and dysfunction.
基金supported by the Seed Fund of Research Institute of Future Food(1-CD54)。
文摘High-fat diet(HFD)consumption induces gut microbiota dysbiosis and neuropsychiatric disorders,including anxiety.Previous research found that Tremella polysaccharide(TP)exhibited neuroprotective effects in vitro and in vivo.This study aimed to investigate the beneficial effects of TP on HFD-induced anxiety-like behaviors and elucidate the underlying mechanisms from the point view of the microbiota-gut-brain axis.Two groups of HFD-induced obese mice were orally gavaged with low dose(TPL,40 mg/kg)and high dose(TPH,400 mg/kg)of TP.A 12-week administration of TPH could significantly improve anxiety-like behaviors in HFD mice.In the hippocampus,microglia activation,the expression of blood-brain barrier(BBB)markers,and the levels of two neurotransmitters(serotonin and norepinephrine)were countered by TPH in mice consuming HFD.Furthermore,TPH improved the intestinal permeability and immune response of the enterocytes in HFD-fed mice.The gut microbiota dysbiosis induced by HFD was also rebalanced by TP treatments,especially in Proteobacteria and its lower taxa.The correlational analysis also suggested that shifts of some microbial genera were closely associated with body weight and the parameters of behavioral tests.Interestingly,fecal microbiota transplantation(FMT)results indicated that fecal microbiota from TPH-treated obese mice could prevent HFD-induced anxiety-like behaviors,suppressed microglia activation and intestinal permeability.In conclusion,the present study indicated that TP intake is a promising dietary intervention strategy to prevent HFD-induced anxiety via the microbiota-gut-brain axis.
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDA26050301-02)。
文摘The global rise in animal protein consumption has significantly amplified the demand for fodder.A comprehensive understanding of the diversity and characteristics of existing fodder resources is essential for balanced nutritional fodder production.This study investigates the diversity and composition of fodder plants and identifies key species for cattle in Zhaotong City,Yunnan,China,while documenting indigenous knowledge on their usage and selection criteria.Ethnobotanical surveys were conducted in 19 villages across seven townships with 140 informants.Data were collected through semi-structured interviews,free listing,and participatory observation,and analyzed using Relative Frequency Citation.A total of 125 taxa(including 106 wild and 19 cultivated)were reported.The most cited family is Poaceae(27 taxa,21.43%),followed by Asteraceae(17 taxa,13.49%),Fabaceae(14 taxa,11.11%),Polygonaceae(9 taxa,7.14%)and Lamiaceae(4 taxa,3.17%).The whole plant(66.04%)and herbaceous plants(84.80%)were the most used parts and life forms.The most cited species were Zea mays,Brassica rapa,Solanum tuberosum,Eragrostis nigra,and Artemisia dubia.Usage of diverse fodder resources reflects local wisdom in managing resource availability and achieving balanced nutrition while coping with environmental and climatic risks.Preferences for certain taxonomic groups are due to their quality as premier fodder resources.To promote integrated crop-livestock farming,we suggest further research into highly preferred fodder species,focusing on nutritional assessment,digestibility,meat quality impacts,and potential as antibiotic alternatives.Establishing germplasm and gene banks for fodder resources is also recommended.
文摘The Nyctereutes procyonoides is highly regarded in the farming and leather industries because of the high value of its fur,which renders artificial feeding a crucial aspect.However,high-fat diets have always been associated with a variety of digestive disorders.This study aimed to investigate the impact of high-fat diets on the gut microbiota and the mechanisms of gut damage in Nyctereutes procyonoides.16S rRNA sequencing demonstrated that high-fat diets caused diarrhea and intestinal damage through alterations in the gut microbiota:a decrease in the abundance of Firmicutes,an increase in the abundance of Proteobacteria and Actinobacteria,and an increase in the abundance of Enterococcaceae,Escherichia coli-Shigella,Clostridium and Lactobacillus.Subsequently,changes in metabolic path-ways,such as amino and fatty acid pathways,were identified by KEGG and COG enrichment analysis,and the TLR4/NF-κB/NLRP3 inflammatory signaling pathway was shown to be activated by high-fat diets.In addition,high-fat diets lead to the accumulation of ROS and MDA and reduce the activity of the antioxidant enzymes GSH-PX and SOD.C orrespondingly,the levels of proinflammatory cytokines(IL-6,IL-1βand TNF-α)were significantly increased,and the apoptosis and necrosis signaling pathways of colonic cells were detected,causing a dramatic decrease in the expression of intestinal tight junction proteins(Occludin,E-cadherin,ZO-1 and ZO-2).In conclusion,high-fat diets altered the structure of the Nyctereutes procyonoides gut microbiota community and led to colon damage.This study provides new insights into the intestinal health of Nyctereutes procyonoides.
基金sponsored by National Natural Science Foundation of China(81800703)Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20231088)+8 种基金Beijing Nova Program(Z201100006820117 and 20220484181)Beijing Municipal Natural Science Foundation(7184252)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities(BMU2021MX013)Peking University Clinical Scientist Training Program(BMU2023PYJH022)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Endocrine and Metabolism Young Scientific Talent Research Project(2022-N-02-01)China Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation。
文摘Maternal consumption of a high-fat diet has been linked to increased risks of obesity and impaired glucose metabolism in offspring.However,the precise epigenetic mechanisms governing these intergenerational effects,particularly during the early stages of offspring development,remain poorly understood.In this study,female C57BL/6J mice were randomly assigned to either a high-fat diet or normal chow diet throughout gestation and lactation.Methylated DNA immunoprecipitation(MeDIP)coupled with microarray analysis was employed to identify differentially methylated genes in the livers of offspring at weaning age.We found that maternal high-fat diet feeding predisposes offspring to obesity and impaired glucose metabolism as early as the weaning period.DNA methylation profile analysis unveiled a significant enrichment of differentially methylated genes within the natural killer(NK)cell-mediated cytotoxicity pathway.MeDIP-PCR validated reduced methylation levels of specific genes within this pathway,including tumour necrosis factorα(TNF-α),phosphoinositide 3-kinase(PI3K),and SHC adaptor protein 1(SHC1).Consistently,the expressions of TNF-α,PI3K,and SHC1 were significantly upregulated,accompanied by elevated serum TNF-αand interleukin-6(IL-6)levels in offspring from dams fed with high-fat diet.Moreover,we assessed the expressions of genes associated with NK cell activities,uncovering a notable rise in hepatic granzyme B levels and a trend towards increased CD107a expression in offspring from dams fed a high-fat diet.In addition,methylation levels of TNF-α,PI3K,and SHC1 promoters were inversely correlated with glucose response during glucose tolerance testing.In conclusion,our findings underscore the critical role of the NK cell-mediated cytotoxicity signaling pathway in mediating DNA methylation patterns,thereby contributing to the programming effects of maternal high-fat diet consumption on offspring glucose metabolism as early as the weaning period.
基金supported by grants from the National Natural Science Foundation of China(32125031)the Fundamental Research Funds for the Central Universities(JUSRP222001)Collaborative Innovation Center for Food Safety and Quality Control,China。
文摘Aflatoxin B_1(AFB_1)is a common contaminant in cereals of global concern,and long-term low-dose exposure can adversely affect human health.Here,we showed that populations with dietary patterns characterized by high-fat diet(HFD)might have an increased risk of exposure to high levels of AFB_1.Our data indicated that chronic exposure of AFB_1 induced“gut-liver axis”injury in mice under HFD and normal diet(ND)patterns.AFB_1 further aggravated hepatic and intestinal injury,and intestinal microbiota disruption in HFD mice.Bifidobacterium breve BAA-2849 intervention analysis showed that liver injury and lipid disorders caused by AFB_1 exposure were alleviated by regulating the proportions of different gut microbes.We demonstrated through a mice model that the populations with a dietary pattern of HFD might be more susceptible to AFB_1 exposure and adverse effects on the gut-liver axis,and the toxicity of AFB_1 exposure can be alleviated by regulating the gut microbiota.
基金supported by the Incubation Fund of Zhongshan Hospital,Fudan University(Xiamen Branch)(2020ZSXMYS24).
文摘Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,although the underlying mechanisms have yet to be determined.We examined the effects of 3ʹ-SL on glycolipid metabolism in mice fed a high-fat diet.Male C57BL/6J mice were divided into 6 groups:2 model control groups(normal and high-fat diets)and 4 intervention groups(Neu5Ac,and low,moderate,and high-dose 3ʹ-SL).After 8 weeks of continuous gavage intervention,mice in the 3ʹ-SL intervention groups had lower body weight and total fat content;reduced fasting blood glucose,triglycerides,low-density lipoproteins and oxidized-low-density lipoproteins;and increased high-density lipoproteins,but no dosage-dependent of 3ʹ-SL intervention was found,moderate-dose 3ʹ-SL intervention as optimal for further exploration.3ʹ-SL intervention could increase respiratory exchange ratio,energy expenditure,and amount of exercise performed.3ʹ-SL increased the colonic abundances of Akkermansia,Lactobacillus,and Bacteroides,and reduced those of Erysipelatoclostridium,Faecalibaculum,and Aldercreutzia.Changes were also observed in colonic metabolites,and liver gene transcript and metabolites,which were mainly enriched in bile secretion,taurine and hypotaurine metabolism,and insulin resistance.Additionally,3ʹ-SL was observed to regulate genes associated with physiological rhythms,including Clock,Per2,Cry1,and Bhihe41.Collectively,our findings indicate that 3ʹ-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets.Compared with Neu5Ac,3ʹ-SL intervention can more effectively ameliorate intestinal flora disorders,enhance bile acid circulation,increase tissue energy expenditure,and reduce lipid synthesis,thereby promoting lipid-lowering effects mediated via the gut-liver axis,and can also enhance energy metabolism and alleviate disorders of glucolipid metabolism by altering physiological rhythms in high fat-diet mice.
基金funding from the European Union -NextGenerationEU through the Italian Ministry of University and Research under PRIN PNRR REG D.R.1718-2022– Project number PRJ-1575 INDICA。
文摘Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.
基金financially supported by the Major Project of Inner Mongolia Science and Technology Department,China(2021ZD0002)National Natural Science Foundation of China,China(32202054)Project Supported by the Shanghai Committee of Science and Technology,China(20DZ2202700)。
文摘Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-induced mice was investigated.Results showed that AVN B significantly inhibited weight gain and improved hepatic and serum lipid biochemical indices.Hepatic RNA-sequencing analysis suggested that AVN B significantly modulates fatty acid(FA)metabolism.Hepatic real-time qualitative polymerase chain reaction(RT-q PCR)and Western blot results indicated that AVN B could alleviate FA synthesis by activating the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)-sterol regulatory element binding protein-1c(SREBP1c)-fatty acid synthase(FAS),and increase FA oxidation by activating the AMPK/carnitine palmitoyltransferase 1A(CPT1A)and peroxisome proliferator-activated receptorα(PPARα).Additionally,AVN B had a regulating effect on ileum lipid metabolism by inhibiting intestinal cell differentiation and downregulating the expression levels of FA absorption-related protein and gene.Moreover,AVN B promoted the growth of beneficial bacteria and fungi such as Coriobacteriaceae_UCG-002,Parvibacter,Enterococcus,and Aspergillus,while decreasing the abundance of Roseburia,unclassified_f_Lachnospiraceae,Cladosporium,Eurotium,unclassified_f_Aspergillaceae and unclassified_f_Ceratocystidaceae.All these results provided new points of the lipid-lowing mechanism of AVNs and oats via the gut-liver axis.
基金supported by the National Natural Science Foundation of China(32471186 and 31771318)the 14th Five-Year-Plan Advantageous and Characteristic Disciplines(Groups)of Colleges and Universities in Hubei Province for Exercise and Brain Science+1 种基金as well as the Leading Talent Program and Innovative Start-up Foundation from Wuhan Sports University to Ning Chensupported by the Hubei Natural Science Foundation(2022CFB929)and China Postdoctoral Science Foundation(2023M732727)to Tong Wu.
文摘It is well known that appropriate aerobic exercise can effectively alleviate fatty liver and enhance brain function.The concept of multi-organ crosstalk coordinating disease progression has become the current research hot topic.However,there remains an urgent need to elucidate its specific mechanisms.This study aimed to explore the impact of a high-fat diet(HFD)on liver health and cognitive function,and to further uncover the regulatory effect of aerobic exercise by liver-specific activating transcription factor 3(Atf3)knockout(ATF3cKO)mice in a“liver-brain”axis mode.The 5-week-old C57BL/6 and ATF3cKO mice were fed with HFD for 32 weeks,and sequentially subjected to aerobic exercise intervention at the 20th week for another 12 consecutive weeks.Meanwhile,C57BL/6 mice were provided with a normal diet as the control group.The functional parameters of liver and brain of all mice were assessed.Cognitive capacity of all mice was assessed by the Morris water maze(MWM).Inflammatory factors in the serum and brain of mice were quantified using enzyme-linked immunosorbent assay(ELISA),and the expression of inflammasomes was detected by immunohistochemistry(IHC).Additionally,the activation of nuclear factor-κB(NF-κB)and phosphoinositide 3-kinase(PI3K)signal pathways was analyzed by Western blotting.In this study,HFD impaired hepatic and brain functions,while aerobic exercise and liver-specific Atf3 knockout suppressed inflammatory factors in the peripheral circulation through hepatoprotective mechanisms,thereby attenuating cerebral inflammation and preserving neurological integrity,as well as mitigating HFD-induced cognitive decline.
基金funded by grants from the National Key R&D Program of China(2016YFD0500604)。
文摘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 circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa 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 diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.
基金supported by Shandong Provincial Natural Science Foundation General Program(No.ZR2022MH213)Shandong Provincial Traditional Chinese Medicine Science and Technology Project General Program(No.M2023241)+1 种基金Jinan Clinical Medical Science and Technology Innovation Program(No.202328013)Qinghai Province High-end Innovative Talents Thousand Talents Program.
文摘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 strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,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 HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,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 pathways.Results 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 size.Moreover,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 activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.
基金sponsored by National Natural Science Foundation of China (81800703 and 81970701)Beijing Nova Program (Z201100006820117 and 20220484181)+7 种基金Beijing Municipal Natural Science Foundation (7184252 and 7214258)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities (BMU2021MX013)Peking University Clinical Scientist Training Program (BMU2023PYJH022)China Endocrine and Metabolism Young Scientific Talent Research Project (2022-N-02-01)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation (G2018030)。
文摘Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,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 metabolites.It 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 genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In 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 intolerance.We 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.
基金Supported by the Preresearch Project of the National Natural Science Foundation of China,No.ZRYY1906the Applied Basic Research Project of the Science and Technology Department of Sichuan Province,No.2021YJ0154+1 种基金the Talent Research Promotion Plan of Xinglin Scholars of Chengdu University of Traditional Chinese Medicine,No.QNXZ2019035the Chengdu University of Traditional Chinese Medicine‘Xinglin Scholars'subject talent research promotion Program(young scholars),No.QNXZ2019037.
文摘BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.METHODS To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with LGZG.The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests.Using a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic steatosis.It effectively controlled blood glucose and food intake while protecting islet cells.Metabolite analysis revealed significant differences between the HFD and HFDLGZG groups.LGZG intervention reduced branched-chain amino acid levels.Levels of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased significantly.IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by qRT-PCR.CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR.LGZG may activate S6K1 via metabolic pathways.These findings lay the groundwork for the potential of LGZG as an IR treatment.
文摘BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migration of lipopolysaccharide(LPS)to other tissues.AIM To evaluate the chronic effects(at 10 and 16 wk)of a high-fat diet(HFD)(with 50%energy as fat)on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice.METHODS Forty adult male mice were divided into four nutritional groups,where the letters refer to the type of diet(control and HFD or HF)and the numbers refer to the period(in weeks)of diet administration:Control diet for 10 wk,HFD for 10 wk,control diet for 16 wk,and HFD for 16 wk.After sacrifice,biochemical,molecular,and stereological analyses were performed.RESULTS The HF groups were overweight,had gut dysbiosis,had a progressive decrease in occludin immunostaining,and had increased LPS concentrations.Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group,consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake.CONCLUSION Chronic HFD intake causes overweight,gut dysbiosis,and morphological and functional alterations of the intestinal barrier after 10 or 16 wk.Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.
基金Supported by Hebei Natural Science Foundation,No.H2022206539Hebei Provincial Government Funded Clinical Talents Training Project,No.ZF2023143.
文摘Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.
基金supported by the National Natural Science Foundation of China(32001679 and 31871801)the Science and Technology Research of Shaanxi Province(2021QFY07-03)+1 种基金supported by the Fundamental Research Funds for the Central Universities(GK202103098)the Scientific and Technological Achievements Commercialization Program of Shaanxi(2023-YDCGZH-13)。
文摘Gut microbiota regulate the activation of adipose browning,which promote energy dissipation and combat diet-induced obesity.Pomegranate peel polyphenols(PPPs)have been shown to reduce obesity,regulate lipid metabolism in adipose tissue,and modulate the composition of gut microbiota in animal fed high-fat diet(HFD).However,the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated.In current study,we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs.The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning,and change the fecal metabolomic profiles in respond to PPPs.Moreover,the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites,such as urolithin A,short-chain fatty acids(SCFAs),and bile acids(BAs),which were associated with activating adipose browning.Therefore,our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity.The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.
基金supported by the National Natural Science Foundation of China(32001679)the Science and Technology Research of Shaanxi Province(2021QFY07-03)+1 种基金the Fundamental Research Funds for the Central Universities(GK202103098)supported by the Scientific and Technological Achievements Commercialization Program of Shaanxi(2023-YD-CGZH-13)。
文摘High-fat diet(HFD)promotes the imbalance of gut microbiota,contributing to the development of metabolic disorders.Pomegranate juice(PJ)and inulin,as dietary polyphenol and dietary fiber respectively,have been reported to ameliorate diet-induced gut microbiota dysbiosis and metabolic disorders.However,the combined effect of PJ and inulin on HFD-induced metabolic disorders has not been elucidated.In current study,we found that the combination of PJ and inulin prevent HFD-induced obesity,dyslipidemia,and gut microbiota dysbiosis.Moreover,the fecal levels of short-chain fatty acids(SCFAs)produced by inulin were increased after inulin combined with PJ.The levels of pomegranate polyphenol metabolites produced by PJ were also increased after PJ combined with inulin,especially pharmacokinetic analysis showed that the presence of inulin enhance the absorption level of urolithin A.Fecal metabolomic analysis found that PJ combined with inulin alter the metabolic status compared with PJ.It was also showed that the levels of SCFAs and pomegranate polyphenol metabolites among groups were correlated with gut microbiota and metabolic disorders indicators.Our results suggested that PJ combined with inulin prevent HFD-induced metabolic disorders,which may be attributed to the promotion of mutual metabolic transformation and absorption of PJ and inulin by gut microbiota.
