AIM： To develop and characterize a practical model of Hepatopulmonary syndrome. （HPS） in rats.METHODS： The experimental animals were randomized into five feeding groups： （1） control （fed standard diet）, （2）...AIM： To develop and characterize a practical model of Hepatopulmonary syndrome. （HPS） in rats.METHODS： The experimental animals were randomized into five feeding groups： （1） control （fed standard diet）, （2） control plus intraperitoneal injection with lipopolysaccharide （LPS）, （3） cirrhosis （fed a diet of maize flour, lard, cholesterol, and alcohol plus subcutaneously injection with carbon tetrachloride （CCI4） oil solution）, （4） cirrhosis plus LPS, and （5） cirrhosis plus glycine and LPS. The blood, liver and lung tissues of rats were sampled for analysis and characterization. Technetium 99m-labeled macroaggregated albumin （Tc99m-MAA） was used to test the dilatation of pulmonary microvasculature.RESULTS： Typical cirrhosis and subsequent hepato- pulmonary syndrome was observed in the cirrhosis groups after an 8 wk feeding period. In rats with cirrhosis, there were a decreased PaO2 and PaCO2 in arterial blood, markedly decreased arterial 02 content, a significantly increased alveolar to arterial oxygen gradient, an increased number of bacterial translocated within mesenteric lymph node, a significant higher level of LPS and tumor necrosis factor-α （TNF-α） in plasma, and a significant greater ratio of Tc99m-MAA brain-overlung radioactivity. After LPS administration in rats with cirrhosis, various pathological parameters got worse and pulmonary edema formed. The predisposition of glycine antagonized the effects of LPS and significantly alleviated various pathological alterations.展开更多
AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched fo...AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention.展开更多
Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determine...Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and i...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.展开更多
AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ...AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver 展开更多
In recent years,high-fat diet(HFD)has been widely applied in aquaculture,which reduces the intestinal health of cultured fish.The current study evaluated the protective effects of nano-selenium(nano-Se)on intestinal h...In recent years,high-fat diet(HFD)has been widely applied in aquaculture,which reduces the intestinal health of cultured fish.The current study evaluated the protective effects of nano-selenium(nano-Se)on intestinal health of juvenile grass carp(Ctenopharyngodon idella)fed with HFD.A total of 135 experimental fish were fed with a regular diet(Con),a HFD(HFD)and a HFD containing nano-Se at 0.6 mg/kg(HSe)for 10 weeks.The results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp(P<0.05).Also,nano-Se(0.6 mg/kg)supplement alleviated intestinal damage caused by the HFD,thus maintaining the integrity of the intestine.Moreover,it significantly up-regulated the expression of genes related to tight junction(ZO-1,claudin-3 and occludin),anti-oxidization(GPx4a and GPx4b),and the protein of ZO-1 in the intestine of juvenile grass carp,which were depressed by the HFD(P<0.05).Furthermore,nano-Se supplementation significantly suppressed the expressions of genes related to the inflammation,including inflammatory cytokines(IL-8,IL-1β,IFN-γ,TNF-αand IL-6),signaling molecules(TLR4,p38 MAPK and NF-kB p65),and protein expression of NF-kB p65 and TNF-αin the intestine of juvenile grass carp which were induced by the HFD(P<0.05).Besides,dietary nano-Se normalized the intestinal microbiota imbalance of juvenile grass carp caused by the HFD through increasing the abundance of the beneficial bacteria,e.g.,Fusobacteria.Finally,dietary nano-Se increased the production of short chain fatty acids(SCFA)in the intestine,especially for butyric acid and caproic acid,which were negatively related to the increase of intestinal permeability and inflammation.In summary,supply of nano-Se(0.6 mg/kg)in HFD could effectively alleviate intestinal injury of juvenile grass carp by improving intestinal barrier function and reducing intestinal inflammation and oxidative stress.These positive effects may be due to the regulation of nano-Se on intestinal microbiota and th展开更多
N6-methyladenosine(m^(6)A)is one of the most abundant modifications on m RNAs and plays important roles in various biological processes.The formation of m^(6)A is catalyzed by a methyltransferase complex(MTC)containin...N6-methyladenosine(m^(6)A)is one of the most abundant modifications on m RNAs and plays important roles in various biological processes.The formation of m^(6)A is catalyzed by a methyltransferase complex(MTC)containing a key factor methyltransferase-like 3(Mettl3).However,the functions of Mettl3 and m^(6)A modification in hepatic lipid and glucose metabolism remain unclear.Here,we showed that both Mettl3 expression and m^(6)A level increased in the livers of mice with high fat diet(HFD)-induced metabolic disorders.Overexpression of Mettl3 aggravated HFDinduced liver metabolic disorders and insulin resistance.In contrast,hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain,reducing lipid accumulation,and improving insulin sensitivity.Mechanistically,Mettl3 depletion-mediated m^(6)A loss caused extended RNA half-lives of metabolism-related genes,which consequently protected mice against HFD-induced metabolic syndrome.Our findings reveal a critical role of Mettl3-mediated m^(6)A in HFD-induced metabolic disorders and hepatogenous diabetes.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
Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk ...Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk factor for multiple metabolic and microvascular diseases including nonalcoholic fatty liver disease(NAFLD),retinopathy,critical limb ischemia,and impaired angiogenesis.Sterile inflammation driven by high-fat diet,increased formation of reactive oxygen species,alteration of intracellular calcium level and associated release of inflammatory mediators,are the main common underlying forces in the pathophysiology of NAFLD,ischemic retinopathy,stroke,and aging brain.This work aims to examine the contribution of the pro-oxidative and pro-inflammatory thioredoxin interacting protein(TXNIP)to the expression and activation of NLRP3-inflammasome resulting in initiation or exacerbation of sterile inflammation in these disease states.Finally,the potential for TXNIP as a therapeutic target and whether TXNIP expression can be modulated using natural antioxidants or repurposing other drugs will be discussed.展开更多
AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed eithe...AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.展开更多
The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ova...The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA).Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups:control group,PCOS group,and PCOS with high-fat diet (HFD) group.Serum hormones were assayed by radioimmunoassay (RIA).The ovaries'were immunohistochemically stained with MIF,and the expression of MIF,p-JNK and p-p38 was detected by Western blotting in ovaries.The serum testosterone level,LH concentration,LH/FSH ratio,fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478,13.809±1.701,1.820±0.404,10.83±1.123 and 1.8692±0.1096)and PCOS with HFD group (6.075±0.439,14.075±1.927,1.779±0.277,10.20±1.377 and 1.7736±0.6851)were significantly higher than those in the control group (4.949±0.337, 2.458±0.509,1.239±0.038,9.53±0.548 and 1.5329±0.7363),but there was no significant difference between the PCOS group and PCOS with HFD group.The expression levels of MIF,p-JNK,and p-p38 in the PCOS group (0.4048±0.013,0.6233±0.093 and 0.7987±0.061)and PCOS withHFD group (0.1929±0.012,0.3346±0.103 and 0.3468±0.031)were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061),but no Significant difference was observed between PCOS group and PCOS with HFD group.It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.展开更多
Background: Animal models of diet-induced obesity(DIO) are commonly used in medical research for mimicking human diseases. There is no universal animal model, and careful evaluation of variety of factors needs to be c...Background: Animal models of diet-induced obesity(DIO) are commonly used in medical research for mimicking human diseases. There is no universal animal model, and careful evaluation of variety of factors needs to be considered when designing new experiments. Here, we investigated the effect of 9 weeks high-fat diet(HFD) intervention, providing 60% energy from fat, on parameters of inflammation and insulin resistance in male C57 BL/6 J mice.Methods: Six weeks old mice were initiated on regular diet(RD) or HFD providing 60 kcal energy from fat for 9 weeks. Fasting blood glucose levels were measured by glucometer, and fasting plasma levels of insulin and proinflammatory cytokines by Luminex assay. Insulin sensitivity was evaluated by using QUICKI and HOMA2 indexes.Results: HFD mice showed ~ 40% higher body weight and ~ 20% larger abdominal circumference, due to an increase in the white adipose tissue mass. Liver examination revealed increased size and higher hepatic lipid accumulation in livers from HFD mice compared to their RD counterparts. Animals from the HFD group were characterized with significantly higher presence of crown-like structures(CLS) in WAT and higher plasma levels of proinflammatory cytokines(TNF-α, IL-6, leptin, MCP-1, PAI-1, and resistin). HFD-fed mice also demonstrated impaired insulin sensitivity(lower QUICKI, higher HOMA-insulin resistance(HOMA-IR), and lower HOMA-percent sensitivity(HOMA-%S)) index values.Conclusion: Male C57 BL/6 J mice on 9 weeks HFD providing 60 kcal energy from fat display impaired insulin sensitivity and chronic inflammation, thus making this DIO mouse model appropriate for studies of early stages of obesity-related pathology.展开更多
Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physi...Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes(especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of r RNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.展开更多
基金awards to University Academic Leaders granted by the Government of Shanxi Province of China to Hui-Ying Zhang and partially by the National Institute of Alcohol Abuse and Alcoholism of United States, grant R01 AA014428 to Cheng Ji
文摘AIM： To develop and characterize a practical model of Hepatopulmonary syndrome. （HPS） in rats.METHODS： The experimental animals were randomized into five feeding groups： （1） control （fed standard diet）, （2） control plus intraperitoneal injection with lipopolysaccharide （LPS）, （3） cirrhosis （fed a diet of maize flour, lard, cholesterol, and alcohol plus subcutaneously injection with carbon tetrachloride （CCI4） oil solution）, （4） cirrhosis plus LPS, and （5） cirrhosis plus glycine and LPS. The blood, liver and lung tissues of rats were sampled for analysis and characterization. Technetium 99m-labeled macroaggregated albumin （Tc99m-MAA） was used to test the dilatation of pulmonary microvasculature.RESULTS： Typical cirrhosis and subsequent hepato- pulmonary syndrome was observed in the cirrhosis groups after an 8 wk feeding period. In rats with cirrhosis, there were a decreased PaO2 and PaCO2 in arterial blood, markedly decreased arterial 02 content, a significantly increased alveolar to arterial oxygen gradient, an increased number of bacterial translocated within mesenteric lymph node, a significant higher level of LPS and tumor necrosis factor-α （TNF-α） in plasma, and a significant greater ratio of Tc99m-MAA brain-overlung radioactivity. After LPS administration in rats with cirrhosis, various pathological parameters got worse and pulmonary edema formed. The predisposition of glycine antagonized the effects of LPS and significantly alleviated various pathological alterations.
文摘AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention.
文摘Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.
文摘AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver
基金This research was funded by the National Key Research and Development Program of China(Project No.2019YFD0901002)Northwest A&F University Young Talent Training Program(2452018030)+2 种基金Science and Technology Research Program of China Se-enriched Research Institute(2018FXZX02-05)Postdoctoral Science Foundation of China(2016M600821)Technical Innovation Guidance Project,Innovation Capability Support Program and Key Research and Development Project of Shaanxi Province(2019QYPY-124,2018TD-021&2018NY-008).
文摘In recent years,high-fat diet(HFD)has been widely applied in aquaculture,which reduces the intestinal health of cultured fish.The current study evaluated the protective effects of nano-selenium(nano-Se)on intestinal health of juvenile grass carp(Ctenopharyngodon idella)fed with HFD.A total of 135 experimental fish were fed with a regular diet(Con),a HFD(HFD)and a HFD containing nano-Se at 0.6 mg/kg(HSe)for 10 weeks.The results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp(P<0.05).Also,nano-Se(0.6 mg/kg)supplement alleviated intestinal damage caused by the HFD,thus maintaining the integrity of the intestine.Moreover,it significantly up-regulated the expression of genes related to tight junction(ZO-1,claudin-3 and occludin),anti-oxidization(GPx4a and GPx4b),and the protein of ZO-1 in the intestine of juvenile grass carp,which were depressed by the HFD(P<0.05).Furthermore,nano-Se supplementation significantly suppressed the expressions of genes related to the inflammation,including inflammatory cytokines(IL-8,IL-1β,IFN-γ,TNF-αand IL-6),signaling molecules(TLR4,p38 MAPK and NF-kB p65),and protein expression of NF-kB p65 and TNF-αin the intestine of juvenile grass carp which were induced by the HFD(P<0.05).Besides,dietary nano-Se normalized the intestinal microbiota imbalance of juvenile grass carp caused by the HFD through increasing the abundance of the beneficial bacteria,e.g.,Fusobacteria.Finally,dietary nano-Se increased the production of short chain fatty acids(SCFA)in the intestine,especially for butyric acid and caproic acid,which were negatively related to the increase of intestinal permeability and inflammation.In summary,supply of nano-Se(0.6 mg/kg)in HFD could effectively alleviate intestinal injury of juvenile grass carp by improving intestinal barrier function and reducing intestinal inflammation and oxidative stress.These positive effects may be due to the regulation of nano-Se on intestinal microbiota and th
基金Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA16030000)the National Key R&D Program(Grant Nos.2017YFA0103803,2018YFA0107703,and 2018YFA0801200)+2 种基金the National Natural Science Foundation of China(Grant Nos.31621004 and 31770872)the Key Research Projects of the Frontier Science of the Chinese Academy of Sciences(Grant Nos.QYZDY-SSW-SMC002 and QYZDB-SSW-SMC022)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.CAS2018133)
文摘N6-methyladenosine(m^(6)A)is one of the most abundant modifications on m RNAs and plays important roles in various biological processes.The formation of m^(6)A is catalyzed by a methyltransferase complex(MTC)containing a key factor methyltransferase-like 3(Mettl3).However,the functions of Mettl3 and m^(6)A modification in hepatic lipid and glucose metabolism remain unclear.Here,we showed that both Mettl3 expression and m^(6)A level increased in the livers of mice with high fat diet(HFD)-induced metabolic disorders.Overexpression of Mettl3 aggravated HFDinduced liver metabolic disorders and insulin resistance.In contrast,hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain,reducing lipid accumulation,and improving insulin sensitivity.Mechanistically,Mettl3 depletion-mediated m^(6)A loss caused extended RNA half-lives of metabolism-related genes,which consequently protected mice against HFD-induced metabolic syndrome.Our findings reveal a critical role of Mettl3-mediated m^(6)A in HFD-induced metabolic disorders and hepatogenous diabetes.
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.
文摘Tissue and systemic inflammation have been the main culprit behind the cellular response to multiple insults and maintaining homeostasis.Obesity is an independent disease state that has been reported as a common risk factor for multiple metabolic and microvascular diseases including nonalcoholic fatty liver disease(NAFLD),retinopathy,critical limb ischemia,and impaired angiogenesis.Sterile inflammation driven by high-fat diet,increased formation of reactive oxygen species,alteration of intracellular calcium level and associated release of inflammatory mediators,are the main common underlying forces in the pathophysiology of NAFLD,ischemic retinopathy,stroke,and aging brain.This work aims to examine the contribution of the pro-oxidative and pro-inflammatory thioredoxin interacting protein(TXNIP)to the expression and activation of NLRP3-inflammasome resulting in initiation or exacerbation of sterile inflammation in these disease states.Finally,the potential for TXNIP as a therapeutic target and whether TXNIP expression can be modulated using natural antioxidants or repurposing other drugs will be discussed.
文摘AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.
基金This project was in part supported by the National Natural Science Foundation of China (No.30973196).
文摘The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA).Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups:control group,PCOS group,and PCOS with high-fat diet (HFD) group.Serum hormones were assayed by radioimmunoassay (RIA).The ovaries'were immunohistochemically stained with MIF,and the expression of MIF,p-JNK and p-p38 was detected by Western blotting in ovaries.The serum testosterone level,LH concentration,LH/FSH ratio,fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478,13.809±1.701,1.820±0.404,10.83±1.123 and 1.8692±0.1096)and PCOS with HFD group (6.075±0.439,14.075±1.927,1.779±0.277,10.20±1.377 and 1.7736±0.6851)were significantly higher than those in the control group (4.949±0.337, 2.458±0.509,1.239±0.038,9.53±0.548 and 1.5329±0.7363),but there was no significant difference between the PCOS group and PCOS with HFD group.The expression levels of MIF,p-JNK,and p-p38 in the PCOS group (0.4048±0.013,0.6233±0.093 and 0.7987±0.061)and PCOS withHFD group (0.1929±0.012,0.3346±0.103 and 0.3468±0.031)were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061),but no Significant difference was observed between PCOS group and PCOS with HFD group.It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.
基金Gerald J.and Dorothy R.Friedman New York Foundation for Medical Research
文摘Background: Animal models of diet-induced obesity(DIO) are commonly used in medical research for mimicking human diseases. There is no universal animal model, and careful evaluation of variety of factors needs to be considered when designing new experiments. Here, we investigated the effect of 9 weeks high-fat diet(HFD) intervention, providing 60% energy from fat, on parameters of inflammation and insulin resistance in male C57 BL/6 J mice.Methods: Six weeks old mice were initiated on regular diet(RD) or HFD providing 60 kcal energy from fat for 9 weeks. Fasting blood glucose levels were measured by glucometer, and fasting plasma levels of insulin and proinflammatory cytokines by Luminex assay. Insulin sensitivity was evaluated by using QUICKI and HOMA2 indexes.Results: HFD mice showed ~ 40% higher body weight and ~ 20% larger abdominal circumference, due to an increase in the white adipose tissue mass. Liver examination revealed increased size and higher hepatic lipid accumulation in livers from HFD mice compared to their RD counterparts. Animals from the HFD group were characterized with significantly higher presence of crown-like structures(CLS) in WAT and higher plasma levels of proinflammatory cytokines(TNF-α, IL-6, leptin, MCP-1, PAI-1, and resistin). HFD-fed mice also demonstrated impaired insulin sensitivity(lower QUICKI, higher HOMA-insulin resistance(HOMA-IR), and lower HOMA-percent sensitivity(HOMA-%S)) index values.Conclusion: Male C57 BL/6 J mice on 9 weeks HFD providing 60 kcal energy from fat display impaired insulin sensitivity and chronic inflammation, thus making this DIO mouse model appropriate for studies of early stages of obesity-related pathology.
文摘Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes(especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of r RNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.
