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
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
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
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
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
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
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
Objective: To observe the differences of partial physiologic indexes including weight, food intake, Lee's index, the wet weight of fat pad, plasma lipids and the genetic expression of LPL mRNA in adipose tissue be...Objective: To observe the differences of partial physiologic indexes including weight, food intake, Lee's index, the wet weight of fat pad, plasma lipids and the genetic expression of LPL mRNA in adipose tissue between obesity-prone rats (OP) and obesity-resistant rats (OR) on a high-fat diet. Methods: After 1 week of free access to a high-fat diet (HFD), 48 rats were separated on the basis of 1 week body weight percentage gained in OP (OP≥P75) or OR (OR≤P25) groups. Rats were continuously fed on the HFD for another 4 weeks. The body weight and food intake were recorded in the course of model-making. And the Lee's index, the plasma lipid and lipoproteins, the wet weight of both epididymal and retroperitoneal fat pad were measured after the rat was killed. And the level of LPL mRNA expression in adipose tissue was detected by Northern Blot technique. Results: ① In OP rats, the speed of body weight gain, the cumulative energy intake, the Lee's index, and the wet weight of fat pad at both epididymal and retroperitoneal sites were significantly higher than those in OR rats, but there was no significant difference in the level of plasma lipid and lipoproteins between these two groups. ② After 1 week and 5 weeks on the high-fat diet, the gain of body weight in OP rats were about 6.45 and 4.25 times of those in OR rats. Meanwhile, the cumulative energy intake in OP rats was only about 1.13 and 1.15 times of those in OR rats. ③ Despite the depressive effect of the high-fat diet on the level of LPL mRNA expression in adipose tissue, there was a significant level of LPL mRNA in adipose tissue of OP rats compared with that in OR rats. Conclusion: The physiologic differences exist between OP and OR rats. Besides a higher level of energy intake, the higher energy efficiency associated with LPL mRNA expression in adipose tissue may also contribute to the enhancement of susceptibility to obesity in OP rats.展开更多
AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and wer...AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and were then infected with a control or an MFN2 expressing adenovirus once a week for 3wk starting from the 9th wk.Blood glucose(BG),plasma insulin and insulin sensitivity of rats were determined at end of the 4th and 8th wk,and after treatment with different amounts of MFN2 expressing adenovirus(108,109 or 1010 vp/kg body weight).BG levels were measured by Accu-chek Active Meter.Plasma insulin levels were analyzed by using a Rat insulin enzymelinked immunosorbent assay kit.Insulin resistance was evaluated by measuring the glucose infusion rate(GIR) using a hyperinsulinemic euglycemic clamp technique.The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway,such as insulin receptor(INSR),insulin receptor substrate 2(IRS2),phosphoinositide-3-kinase(PI3K),protein kinase beta(AKT2) and glucose transporter type 2(GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting.RESULTS:After the end of 8wk,the body weight of rats receiving the normal control diet(ND) and the HFD was not significantly different(P>0.05).Compared with the ND group,GIR in the HFD group was significantly decreased(P<0.01),while the levels of BG,triglycerides(TG),total cholesterol(TC) and insulin in the HFD group were significantly higher than those in the ND group(P<0.05).Expression of MFN2 mRNA and protein in liver of rats was significantly downregulated in the HFD group(P<0.01) after 8 wk of HFD feeding.The expression of INSR,IRS2 and GLUT2 were down-regulated markedly(P<0.01).Although there were no changes in PI3K-P85 and AKT2 expression,their phosphorylation levels were decreased significantly(P<0.01).After intervention with MFN2 expressing adenovirus for 3wk,the expression of MFN2 mRNA and protein levels were up-regulated(P<0.01).There was no difference in body weight of rats between the groups.The levels of BG,TG,TC and insulin in rats were lower than those in the Ad group(P<0.05),but GIR in rats infected with Ad-MFN2 was significantly increased(P<0.01),compared with the Ad group.The expression of INSR,IRS2 and GLUT2 was increased,while phosphorylation levels of PI3K-P85 and AKT2 were increased(P<0.01),compared with the Ad group.CONCLUSION:HFDs induce insulin resistance,and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.展开更多
Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC...Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.展开更多
AIM To identify the effect of hydrogen-rich water(HRW) and electrolyzed-alkaline water(EAW) on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1) Regular diet(RD)/...AIM To identify the effect of hydrogen-rich water(HRW) and electrolyzed-alkaline water(EAW) on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1) Regular diet(RD)/regular water(RW);(2) high-fat diet(HFD)/RW;(3) RD/EAW; and(4) HFD/EAW. Weight and body composition were measured. After twelve weeks, animals were sacrificed, and livers were processed for histology and reverse-transcriptase polymerase chain reaction. A similar experiment was performed using HRW to determine the influence and importance of molecular hydrogen(H2) in EAW. Finally, we compared the response of hepatocytes isolated from mice drinking HRW or RW to palmitate overload.RESULTS EAW had several properties important to the study:(1) pH = 11;(2) oxidation-reduction potential of-495 mV; and(3) H2 = 0.2 mg/L. However, in contrast to other studies, there were no differences between the groups drinking EAW or RW in either the RD or HFD groups. We hypothesized that the null result was due to low H2 concentrations. Therefore, we evaluated the effects of RW and low and high HRW concentrations(L-HRW = 0.3 mg H2/L and H-HRW = 0.8 mg H2/L, respectively) in mice fed an HFD. Compared to RW and L-HRW, H-HRW resulted in a lower increase in fat mass(46% vs 61%), an increase in lean body mass(42% vs 28%), and a decrease in hepatic lipid accumulation(P < 0.01). Lastly, exposure of hepatocytes isolated from mice drinking H-HRW to palmitate overload demonstrated a protective effect from H2 by reducing hepatocyte lipid accumulation in comparison to mice drinking regular water.CONCLUSION H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice.展开更多
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, succ...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.展开更多
Objective： The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection. Methods： Wistar rats were fed with ...Objective： The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection. Methods： Wistar rats were fed with a high-fat diet for 8 weeks followed by a one-time injection of 25 or 35 mg/kg streptozotocin to induce type 2 diabetes. Then the diabetic rats were fed with regular diet/high-fat diet for 4 weeks. Changes in biochemical parameters were monitored during the 4 weeks. Results： All the rats developed more severe dyslipidemia and hepatic dysfunction after streptozotocin injection. The features of 35 mg/kg streptozotocin rats more resembled type 1 diabetes with decreased body weight and blood insulin. Rats with 25 mg/kg streptozotocin followed by normal diet feeding showed normalized blood glucose level and pancreatic structure, indicating that normal diet might help recovery from certain symptoms of type 2 diabetes. In comparison, diabetic rats fed with high-fat diet presented decreased but relatively stable blood glucose level, and this was significantly higher than that of the control group（P〈0.05）. Conclusions： This model easily recovers with normal diet feeding. A high-fat diet is suggested as the background diet in future pharmacological studies using this model.展开更多
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 ...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.展开更多
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 ...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.展开更多
Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immuni...Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance(IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease(NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides(PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.展开更多
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 col...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).展开更多
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.
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 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.
文摘Objective: To observe the differences of partial physiologic indexes including weight, food intake, Lee's index, the wet weight of fat pad, plasma lipids and the genetic expression of LPL mRNA in adipose tissue between obesity-prone rats (OP) and obesity-resistant rats (OR) on a high-fat diet. Methods: After 1 week of free access to a high-fat diet (HFD), 48 rats were separated on the basis of 1 week body weight percentage gained in OP (OP≥P75) or OR (OR≤P25) groups. Rats were continuously fed on the HFD for another 4 weeks. The body weight and food intake were recorded in the course of model-making. And the Lee's index, the plasma lipid and lipoproteins, the wet weight of both epididymal and retroperitoneal fat pad were measured after the rat was killed. And the level of LPL mRNA expression in adipose tissue was detected by Northern Blot technique. Results: ① In OP rats, the speed of body weight gain, the cumulative energy intake, the Lee's index, and the wet weight of fat pad at both epididymal and retroperitoneal sites were significantly higher than those in OR rats, but there was no significant difference in the level of plasma lipid and lipoproteins between these two groups. ② After 1 week and 5 weeks on the high-fat diet, the gain of body weight in OP rats were about 6.45 and 4.25 times of those in OR rats. Meanwhile, the cumulative energy intake in OP rats was only about 1.13 and 1.15 times of those in OR rats. ③ Despite the depressive effect of the high-fat diet on the level of LPL mRNA expression in adipose tissue, there was a significant level of LPL mRNA in adipose tissue of OP rats compared with that in OR rats. Conclusion: The physiologic differences exist between OP and OR rats. Besides a higher level of energy intake, the higher energy efficiency associated with LPL mRNA expression in adipose tissue may also contribute to the enhancement of susceptibility to obesity in OP rats.
文摘AIM:To investigate the effects of mitofusin-2(MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet(HFD).METHODS:Rats were fed with a control or HFD for 4 or 8 wk,and were then infected with a control or an MFN2 expressing adenovirus once a week for 3wk starting from the 9th wk.Blood glucose(BG),plasma insulin and insulin sensitivity of rats were determined at end of the 4th and 8th wk,and after treatment with different amounts of MFN2 expressing adenovirus(108,109 or 1010 vp/kg body weight).BG levels were measured by Accu-chek Active Meter.Plasma insulin levels were analyzed by using a Rat insulin enzymelinked immunosorbent assay kit.Insulin resistance was evaluated by measuring the glucose infusion rate(GIR) using a hyperinsulinemic euglycemic clamp technique.The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway,such as insulin receptor(INSR),insulin receptor substrate 2(IRS2),phosphoinositide-3-kinase(PI3K),protein kinase beta(AKT2) and glucose transporter type 2(GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting.RESULTS:After the end of 8wk,the body weight of rats receiving the normal control diet(ND) and the HFD was not significantly different(P>0.05).Compared with the ND group,GIR in the HFD group was significantly decreased(P<0.01),while the levels of BG,triglycerides(TG),total cholesterol(TC) and insulin in the HFD group were significantly higher than those in the ND group(P<0.05).Expression of MFN2 mRNA and protein in liver of rats was significantly downregulated in the HFD group(P<0.01) after 8 wk of HFD feeding.The expression of INSR,IRS2 and GLUT2 were down-regulated markedly(P<0.01).Although there were no changes in PI3K-P85 and AKT2 expression,their phosphorylation levels were decreased significantly(P<0.01).After intervention with MFN2 expressing adenovirus for 3wk,the expression of MFN2 mRNA and protein levels were up-regulated(P<0.01).There was no difference in body weight of rats between the groups.The levels of BG,TG,TC and insulin in rats were lower than those in the Ad group(P<0.05),but GIR in rats infected with Ad-MFN2 was significantly increased(P<0.01),compared with the Ad group.The expression of INSR,IRS2 and GLUT2 was increased,while phosphorylation levels of PI3K-P85 and AKT2 were increased(P<0.01),compared with the Ad group.CONCLUSION:HFDs induce insulin resistance,and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.
基金supported by the National Natural Science foundation of China(No.31071531)the Scientific Research Fund of the Hunan Provincial Education Department(No.14A071)the China National Tobacco Corp Hunan Branch(15-17Aa04)
文摘Objective To reveal the effects and related mechanisms of chlorogenic acid(CGA)on intestinal glucose homeostasis.Methods Forty male Sprague-Dawley rats were randomly and equally divided into four groups:normal chow(NC),high-fat diet(HFD),HFD with low-dose CGA(20 mg/kg,HFD-LC),and HFD with high-dose CGA(90 mg/kg,HFD-HC).The oral glucose tolerance test was performed,and fast serum insulin(FSI)was detected using an enzyme-linked immunosorbent assay.The m RNA expression levels of glucose transporters(Sglt-1 and Glut-2)and proglucagon(Plg)in different intestinal segments(the duodenum,jejunum,ileum,and colon)were analyzed using quantitative real-time polymerase chain reaction.SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.Results At both doses,CGA ameliorated the HFD-induced body weight gain,maintained FSI,and increased postprandial 30-min glucagon-like peptide 1 secretion.High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression.Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.Conclusion An HFD can cause a glucose metabolism disorder in the rat intestine and affect body glucose homeostasis.CGA can modify intestinal glucose metabolism by regulating the expression of intestinal glucose transporters and Plg,thereby controlling the levels of blood glucose and insulin to maintain glucose homeostasis.
基金Tel Hai College Research funding Grant,No.25-2-14-114
文摘AIM To identify the effect of hydrogen-rich water(HRW) and electrolyzed-alkaline water(EAW) on high-fat-induced non-alcoholic fatty acid disease in mice.METHODS Mice were divided into four groups:(1) Regular diet(RD)/regular water(RW);(2) high-fat diet(HFD)/RW;(3) RD/EAW; and(4) HFD/EAW. Weight and body composition were measured. After twelve weeks, animals were sacrificed, and livers were processed for histology and reverse-transcriptase polymerase chain reaction. A similar experiment was performed using HRW to determine the influence and importance of molecular hydrogen(H2) in EAW. Finally, we compared the response of hepatocytes isolated from mice drinking HRW or RW to palmitate overload.RESULTS EAW had several properties important to the study:(1) pH = 11;(2) oxidation-reduction potential of-495 mV; and(3) H2 = 0.2 mg/L. However, in contrast to other studies, there were no differences between the groups drinking EAW or RW in either the RD or HFD groups. We hypothesized that the null result was due to low H2 concentrations. Therefore, we evaluated the effects of RW and low and high HRW concentrations(L-HRW = 0.3 mg H2/L and H-HRW = 0.8 mg H2/L, respectively) in mice fed an HFD. Compared to RW and L-HRW, H-HRW resulted in a lower increase in fat mass(46% vs 61%), an increase in lean body mass(42% vs 28%), and a decrease in hepatic lipid accumulation(P < 0.01). Lastly, exposure of hepatocytes isolated from mice drinking H-HRW to palmitate overload demonstrated a protective effect from H2 by reducing hepatocyte lipid accumulation in comparison to mice drinking regular water.CONCLUSION H2 is the therapeutic agent in electrolyzed-alkaline water and attenuates HFD-induced nonalcoholic fatty liver disease in mice.
基金Supported by National Institute of Health,No.NCI-3R01CA121249-08S1,NCCIH-K99AT009206 and No.NCI-1R21CA191966
文摘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.
文摘Objective： The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection. Methods： Wistar rats were fed with a high-fat diet for 8 weeks followed by a one-time injection of 25 or 35 mg/kg streptozotocin to induce type 2 diabetes. Then the diabetic rats were fed with regular diet/high-fat diet for 4 weeks. Changes in biochemical parameters were monitored during the 4 weeks. Results： All the rats developed more severe dyslipidemia and hepatic dysfunction after streptozotocin injection. The features of 35 mg/kg streptozotocin rats more resembled type 1 diabetes with decreased body weight and blood insulin. Rats with 25 mg/kg streptozotocin followed by normal diet feeding showed normalized blood glucose level and pancreatic structure, indicating that normal diet might help recovery from certain symptoms of type 2 diabetes. In comparison, diabetic rats fed with high-fat diet presented decreased but relatively stable blood glucose level, and this was significantly higher than that of the control group（P〈0.05）. Conclusions： This model easily recovers with normal diet feeding. A high-fat diet is suggested as the background diet in future pharmacological studies using this model.
基金the support of the "Cooperative Research Program for Agriculture Science & Technology Development (Project No.PJ009582)" of the Rural Development Administration.Republic of Korea
文摘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.
基金supported by the Cooperative Research Program for Agriculture Science & Technology Development (No.PJ01134802)
文摘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.
基金financially supported by the Natural Science Foundation of Hunan Province, China (2019JJ40272)the Scientific Research Foundation of Hunan Provincial Education Department, China (20C1676)the Scientific Research Foundation of Shaoyang College, China (2020HX122)。
文摘Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance(IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease(NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides(PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.
基金Binational Science Foundation(BSF)grant number 2015077German Israeli Science Foundation(GIF)grant I-63-410.20-2017+1 种基金Israeli Science Foundation(ISF)grant 1085/18core fund from Tel Aviv University。
文摘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).
