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

Flaxseed oil(FSO)rich in n-3 polyunsaturated fatty acids(PUFAs)can protect against obesity and insulin resistance,but the underlying mechanism is unknown.An 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 mice.FSO ameliorated the gut microbial dysbiosis by increasing the community diversity and the abundance of Clostridiales and Ruminococcaceae.These effects were associated with the regulation of bile acid(BAs)in the feces.FSO 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 pathway.Further 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 lipogenesis.The results of this study suggest that FSO modulates serum lipid concentrations by regulating the gut microbiota,FXR-FGF15 signaling and BA metabolism.

Time-dependent impact of a high-fat diet on the intestinal barrier of male mice

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.

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

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.

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

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.

SESN2 ablation weakens exercise benefits on resilience of gut microbiota following high-fat diet consumption in mice

Gut dysbiosis is associated with several pathological processes.Previous study showed that regular exercise can protect against dysmetabolism in high-fat diet(HFD)fed mice through butyrate-SESN2 pathway,and SESN2 ablation weakened the protective effects of exercise.Here,we investigated whether SESN2-defi ciency suppresses the exercise response to microbiota composition and subsequently reduces the benefi ts of exercise on dysmetabolism induced by HFD.Wild type(WT)and SESN2^(-/-)mice were assigned to fi ve-groups,fed with either normal chow or HFD and with or without exercise training for 15-week.Fecal microbiota composition and function were assessed by 16S rRNA sequencing.The sequencing results showed that SESN2^(-/-)mice displayed differed microbiome profile from WT mice.Exercise enriched the microflora diversity and increased the benefi cial microbial species in WT mice,and SESN2 ablation weakened the benefi cial effects of exercise on microbial resilience following HFD consumption.Moreover,network analysis revealed that exercise increased correlation density and clustering of operational taxonomic units in WT mice only.KEGG demonstrated that some dominant metabolism-related enzymes and modules increased in SESN2^(-/-)mice.Our results indicated that the effects of exercise on metabolism are associated with the perturbations of gut microbiota composition and function,suggesting that SESN2 contributes to maintain metabolic homeostasis.

Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet

Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.Human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.

The prevention of high-fat diet-induced non-alcoholic fatty liver disease in mice by Fucoidan

Objective:To study the preventive effect of fucoidan on non-alcoholic fatty liver disease induced by high fat diet.Methods:The experimental mice were randomly divided into three groups:control group,high-fat diet group and fucoidan intervention group.The control group was fed a standard diet,and the other two groups were fed a high-fat diet.The control group and the high-fat diet group were given normal saline intragastric administration every day,and the intervention group was given intragastric administration of fucoidan polysaccharide solution at a dose of 100 mg∙kg^(-1)∙d^(-1) once a day for continuous intervention for 12 weeks.After the last intragastric administration for 12 h,the body weight and liver weight of each group of mice were measured,and the liver index was calculated.The contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)in liver tissues of mice in each group were detected by biochemical kit.Hematoxylin-eosin staining(HE)was used to compare the pathological morphological changes of liver tissue in each group.The contents of inflammatory factor interleukin-6(IL-6),tumor necrosis factor(TNF-α)and oxidative stress index malondialdehyde(MDA),and the activities of glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD)in liver tissues of mice in each group were determined.Results:Compared with the control group,the body weight and liver index of mice receiving high fat diet increased significantly(P<0.01).In addition,the contents of TG,TC,AST and ALT in liver tissue of high-fat diet group were significantly increased compared with that of control group(P<0.01).The liver tissue of mice in the high-fat diet group also showed significant pathological changes,accompanied by increased expression of inflammatory factors and a significant increase in oxidative stress response.However,compared with the mice in the high-fat diet group,the above indexes were significantly improved in the liver tissue of the mice treated with fucoidan(P<0.01).Conclusion:Fucoidan can inhibit liver lipid deposition,liver inflammation and oxidative stress induced by high fat diet.

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

Background:Type 2 diabetes(T2D)is an adult-onset and obese form of diabetes caused by an interplay between genetic,epigenetic,and environmental components.Here,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)challenges.Methods:Mice were fed with either the HFD or the standard chow diet(control group)for 12 weeks starting at the age of 8 weeks.At week 5 of the experiment,half of the mice of each diet group were infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria strains.Throughout 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 mice.Results:Statistical analysis has shown the significance of phenotypic variations between the CC lines,which have different genetic backgrounds and sex effects in different experimental groups.The heritability of the studied phenotypes was estimated and ranged between 0.45 and 0.85.We applied machine learning methods to make an early call for T2D and its prognosis.The results showed that classification with random forest could reach the highest accuracy classification(ACC=0.91)when all the attributes were used.Conclusion: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).

Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice

Objective:To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract(GCBE) in high-fat diet(HFD)-induced obese mice.Methods:Obesity was induced in mice using a HFD for four weeks.Then,mice were fed only HFD or HFD with GCBE at 50,100,and 200 mg/kg.Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay.Body fat reduction was measured through dual-energy X-ray absorptiometry.Results:In HFD-induced obese mice,GCBE treatment significantly decreased body weight gain,liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones,like adiponectin and leptin.GCBE treatment decreased mR NA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver,and decreased the corresponding protein expression.Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE.GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased.Conclusions:GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver.

Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients.

The beneficial effects of Tartary buckwheat (Fagopyrum tataricum Gaertn.) on diet-induced obesity in mice are related to the modulation of gut microbiota composition

The gut is home to a large number of intestinal microbiota that play an important role in the metabolism and immune system of the host.A growing body of evidence suggests that a high-fat diet is closely associated with many metabolic disorders,including fatty liver and type 2 diabetes.According to reports,Tartary buckwheat extract has a positive effect on intestinal microbiota in animals.The effects of Tartary buckwheat on biochemical indexes and intestinal microflora in mice were studied.Tartary buckwheat protein(FGP),Tartary buckwheat resistant starch(FGS)and Tartary buckwheat flour(FGF)alleviated organ damage in mice and lowered the atherosclerotic index(AI)in plasma.Otherwise,principal coordinate analysis(PCoA)showed that intestinal bacterial structure of FGF were separated apparently from other groups.The Firmicutes/Bacteroidetes(F/B)value of the high-fat(HF)-FGF group was significantly lower than that of the HF-FGP and HF-FGS groups.FGF significantly increases the abundance of beneficial bacteria such as Bifidobacterium,while decreasing the abundance of lipopolysaccharide(LPS)-producing bacteria.Observation of blood lipid metabolism parameters and analysis of the intestinal microbiota suggested that FGF can be more effective than FGP and FGS to reduce the effects of a high-fat diet in mice,restoring the blood parameters to values similar of those in mice fed a low-fat diet.FGF may be used to prevent or treat blood lipid metabolism disorders and intestinal microbiota disorders in mice fed a high-fat diet.

In vivo activities of the structured lipids-1,3-dioleic acid 2-palmitic acid triglyceride(OPO)in high-fat diet mice

High-energy diets and lipid metabolism can lead to high levels of total cholesterol,a decrease in antioxidant,enzyme activity,and an increase in oxidative stress and dyslipidemia biomarker.In this study,the in vivo antihyperlipidemic and antioxidant effects of 1,3-dioleoyl-2-palmitoyl triglyceride(OPO)using a high fat-diet model were investigated.The mice were divided into groups including high-fat model group(HF),auxiliary group(AG),positive Control group(PC),low OPO dose group(LO),medium OPO dose group(MO)and high OPO.OPO was administrated to 60 hyperlipidemia induced male Kunming mice at the dosage of 200,400 and 800 mg/kg•d body weight,for 35 days.The results showed that the administration of OPO decreased the body weight from 43.92 g in HF to 37.74 g in HO group,liver index from 3.94%in HF to 3.43 in HO group and kidney index from 1.38 in HF%to 1.17%in HO group.The administration of OPO significantly decreased hyperlipidemia mice's serum triglyceride,total cholesterol,and low-density lipoprotein cholesterol levels at P<0.05.High-density lipoprotein cholesterol levels were increased with reductions of visceral hypertrophy and fat accumulation in model mice.Furthermore,in the HO group,superoxide dismutase,catalase and glutathione peroxidase levels increased significantly by 27.39,38.33 and 22.90%at(P<0.05),respectively.OPO also significantly reduced the enzyme activity of aspartate aminotransferase and alanine aminotransferase in serum at P<0.05.These findings suggested that OPO has potential use in hyperlipidemia treatment and other health-related complications.

Effects of Polygonatum sibiricum Polysaccharide (PSP) on Inflammatory Factors in Rats Fed on High-fat Diet

[Objectives]This study was conducted to explore the effects of Polygonatum sibiricum polysaccharide(PSP)on chronic intestinal inflammation caused by high-fat diet.[Methods]Thirty five male healthy SD rats were randomly divided into a normal control group(NC,normal diet,n=10)and a high-fat diet group(HF,high-fat diet,n=25).After 8 weeks,an obesity model was established.The HF group was randomly divided into an HF group and a PSP treatment group[PSP,300 mg/(kg·d)].After 6 weeks of intervention with PSP,rat serum was collected,and the spleen and thymus were stripped,and weighed.Serum IgG,IgM,LPS and IL-1βand IL-6 contents were detected by ELISA,and HE staining was adopted to observe the pathological changes of the colon tissue.[Results]PSP reduced the level of LPS caused by high-fat diet and the levels of inflammatory factors IL-6 and TNF-α,increased the indexes of the thymus and spleen serving as immune organs,increased IgG and IgM contents,and alleviated pathological damage to the colon tissue caused by high-fat diet.[Conclusions]This study provides a theoretical basis and experimental basis for the development of drugs for treating metabolic diseases such as obesity and inflammation.

Effect of Mongolian Vinegar Soaked Licorice on Liver Fibrosis Induced by Carbon Tetrachloride Combined with High-fat Diet in Rats

[Objectives]To determine the improvement effect of vinegar soaked licorice on liver fibrosis induced by carbon tetrachloride(CCl_(4))combined with high-fat diet in rats.[Methods]Subcutaneous injection of 40%-60%CCl_(4)olive oil solution(0.3 mL/100 g)combined with a high-fat diet was used for 5 weeks to establish the rat model with liver fibrosis.After the modeling,the rats were divided into a low dose(0.8 g/kg),a medium dose(2.5 g/kg),a high dose(5 g/kg)group,a colchicine(1.5 mg/kg)positive group,and a vinegar group(2 mL/kg).The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels in the rats were measured automatically.The serum hyaluronic acid(HA)was detected by radioimmunoassay,and the serum laminin(LN)and procollagen type III peptide(PIIIP)levels were measured by enzyme-linked immunoassay.Liver histopathological morphological changes were observed by HE and Masson staining,and expressions of cytochrome CYP2E1 and transcription factor Nrf2 were detected by immunohistochemistry.[Results]The rat liver fibrosis model was established successfully at the 6~(th)week.Compared with the model group,the levels of ALT,AST,HA,LA,PIIIP,CYP2E1 and Nrf2 of all the examined indexes in the dosing group were decreased(P<0.05).As shown in the pictures of liver pathological tissue sections,the liver fibrosis was significantly alleviated in the positive group and the 3 administration groups.[Conclusions]Vinegar soaked licorice can significantly improve the liver fibrosis induced by carbon tetrachloride combined with high-fat diet in rats,and the effect of the high-dose group was similar to that of the positive group.

Effects of Polygonatum sibiricum Polysaccharide on Antioxidant Capacity of the Liver in High-fat Diet Rats

[Objectives]This study was conducted to investigate the effects of Polygonatum sibiricum polysaccharide(PSP)on antioxidant function in high-fat diet obese rats.[Methods]Thirty five healthy male SD rats were selected to establish an obesity model after feeding a high-fat for 8 weeks.They were then randomly divided into a normal group(NC),a high-fat diet group(HF),and an HF+P.sibiricum polysaccharide group[HF+PSP,300 mg/(kg·d)].After 6 weeks of PSP intervention,the serum and liver of rats were collected,and the activity of aspartate transaminase(AST)and alanine aminotransferase(ALT)in serum,the enzyme activity of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in liver tissue were measured.The pathological changes of liver tissue were observed by HE staining.[Results]Compared with the HF group,PSP could effectively inhibit obesity caused by high-fat diet.It reduced body weight and serum AST and ALT levels,increased the contents of T-SOD,CAT and GSH-Px in the liver,and inhibited the accumulation of MDA content,thereby reducing damage to liver cells caused by a high-fat diet.It indicated that PSP could effectively inhibit obesity in high-fat diet rats and enhance their antioxidant capacity.[Conclusions]This study provides a reference for the study of the antioxidant capacity of PSP.

Effects of Polygonatum odoratum Polysaccharide on Reproductive Hormones in Male Rats Fed a High-fat Diet

[Objectives]This study was conducted to investigate the effects of Polygonatum odoratum polysaccharide(POP)on organ relative weights and reproductive hormone levels in male rats fed a high-fat diet.[Methods]Thirty healthy male Sprague-Dawley(SD)rats were randomly divided into two groups according to their body weight:10 in normal control group(Group NC,n=10)and 20 in experimental group(n=20).The rats in experimental group were fed a high-fat diet for eight weeks before they were further randomly divided into two groups:high fat group(Group HF)and high fat+400 mg/(kg·d)POP group(Group HF+POP).In Group HF+POP,the rats were administered with POP for another six weeks,before their blood plasma was collected,and the relative weights of their testis and epididymis were calculated.The plasma levels of testosterone(T),estrogen(E2),follicle-stimulating hormone(FSH),cortisol(C)and luteinizing hormone(LH)were measured by radioimmunoassay,and the plasma levels of sex hormone-binding globulin(SHBG)and insulin-like growth factor-1(IGF-1)were determined by enzyme-linked immunosorbent assay.[Results]Compared with Group HF,POP could effectively inhibit rat obesity caused by high-fat diets,increase the relative weights of their testis and epididymis,plasma levels of LH,E2,FSH,T,SHBG and IGF-1,and reduce the plasma level of E2.[Conclusions]Polygonatum odoratum polysaccharide(POP)is able to effectively regulate the level of reproductive hormones in high-fat diet fed rats,and helps to protect their reproductive function.

Ketogenic diet alleviates cognitive dysfunction and neuroinflammation in APP/PS1 mice via the Nrf2/HO-1 and NF-κB signaling pathways

Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain.The ketogenic diet,a widely recognized therapeutic intervention for refractory epilepsy,has recently been proposed as a potential treatment for a variety of neurological diseases,including Alzheimer's disease.However,the efficacy of ketogenic diet in treating Alzheimer's disease and the underlying mechanism remains unclear.The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer's disease.Male amyloid precursor protein/presenilin 1(APP/PS1)mice were randomly assigned to either a ketogenic diet or control diet group,and received their respective diets for a duration of 3 months.The findings show that ketogenic diet administration enhanced cognitive function,attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice,and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway.Collectively,these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer's disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation.This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer's disease.

Uridine dynamic administration affects the circadian variation of bile acid metabolism in high-fat-diet-fed mice

High-fat diet(HFD)is demonstrated to disturb the bile acid metabolism.The rhythm of bile acid metabolism can also be affected by uridine,whose metabolism exhibits a daily rhythm.However,the mechanism of dynamic uridine administration affecting bile acid during HFD remains unclear.In this study,C57BL/6J mice were fed HFD(the control group;CON)or HFD with oral administration of uridine in the daytime(DUR)and nighttime(NUR)to investigate the mechanism of the effect of uridine on the bile acid.This study showed that the mRNA expression of uridine transporters and circadian clock genes in the jejunum was affected by zeitgeber time(ZT)(P<0.001).Genes related to the metabolism of pyrimidines in the liver showed a high dependence on daily rhythm(P<0.01),and DUR remarkably up-regulated the expression of ribonucleotide reductase regulatory subunit M2(RRM2)(P<0.05)compared to the CON group.Importantly,the mRNA expression of bile acids nuclear receptors,bile acid synthesis,and transporters in the liver showed significantly rhythmically changed(P<0.05),and the expression of cholesterol 7-alpha-hydroxylase(CYP7A1),fibroblast growth factor receptor 4(FGFR4),Na^(+)/taurocholate co transporting polypeptide(NTCP),and bile salt export pump(BSEP)mRNAs of mice with uridine administration increased significantly(P<0.05).The mRNA expression of the transporters of cholesterol and bile acids in the ileum was also affected by ZT(P<0.01)and significantly dependent on uridine administration(P<0.05).The expression of FXR and SHP was significantly affected by ZT and uridine,respectively.In conclusion,dynamic administration of uridine could regulate the rhythm of gene expression of pyrimidine and bile acid metabolism in the liver and ileum of HFD-fed mice,which contributed to the further study of circadian rhythmic physiological and pathological changes of bile acids.

Effects of ginseng dietary supplementation on a high-Fat diet-induced obesity in C57BL/6 Mice

Excess caloric intake increases the amount of adipose tissue and contributes to metabolic disorders in disrupted metabolic homeostasis.This study aimed to investigate the anti-obesity effects of ginseng and the alternation of gut microbiota composition in high-fat diet(HFD)-induced obesity.The results showed that HFD treatment influenced body weight gain,adipose tissue accumulation and biochemical parameter changes.Compared to the HFD group,ginseng supplementation of HFD-fed mice decreased body weight,adipose tissue mass,total cholesterol(T-CHO)and high-density lipoprotein(HDL)/low-density lipoprotein(LDL)ratio.To analysis the alterations of gut microbiota,ginseng in dietary supplements decreased Firmicutes abundance and increased Bacteroidetes abundance.Taken together,these findings suggest ginseng may modulate the energy storage and alter gut microbiota composition.