As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a...As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a mod-erate(10 weeks) and a prolonged(30 weeks) high fructose and saturated fatty acid(HFS) diet on plasma FA com-position in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to es-tablish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7)(decreased) and 20:4(n-6)(increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.展开更多
Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring...Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.展开更多
Insulin resistance is an increasingly severe public health issue worldwide,affecting millions and significantly raising the risk of diabetes and cardiovascular diseases.Despite this,current treatment options remain li...Insulin resistance is an increasingly severe public health issue worldwide,affecting millions and significantly raising the risk of diabetes and cardiovascular diseases.Despite this,current treatment options remain limited,which has heightened interest in exploring interventions based on natural compounds.This study investigates the potential of Lycium barbarum leaf flavonoids(LBLF)to improve insulin resistance induced by high fructose in mice,with a focus on the mechanisms related to blood glucose regulation and gut microbiota composition.Research results show that,compared to the high fructose model group,treatment with metformin hydrochloride and rutin reduced fasting blood glucose levels by 32.06%and 18.94%,respectively.LBLF treatment at various doses decreased fasting blood glucose levels by 12.29%,19.02%,and 32.98%,and insulin levels by 26.50%,11.04%,and 28.23%,respectively,demonstrating its effective ability to regulate blood glucose levels.It was also found that LBLF effectively regulated lipid disorders,significantly reduced oxidative stress in the liver,and protected liver function.Liver transcriptomic analysis suggests that LBLF may improve insulin resistance by regulating gene expression in the MAPK and retinol metabolism signaling pathways.Additionally,gut microbiota diversity analysis revealed that LBLF treatment reduced the Firmicutes/Bacteroidetes(F/B)ratio,which is asso-ciated with obesity and metabolic disorders,thereby optimizing the gut microbiota structure disrupted by high fructose intake.These results highlight the therapeutic potential of LBLF in managing insulin resistance and associated metabolic disorders,providing a theoretical basis for further research into its broader applications.展开更多
The intake of sugars,especially glucose and fructose,has significantly increased with the change of lifestyle.Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases.Fructose d...The intake of sugars,especially glucose and fructose,has significantly increased with the change of lifestyle.Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases.Fructose directly mediates innate immune responses;however,whether it can directly regulate T-cell immunity remains unknown.We show that high fructose consumption accelerates the development of inflammatory bowel disease(IBD)by promoting the generation of T helper 1(Th1)and T helper 17(Th17)cells.It was demonstrated that fructose promotes the differentiation of Th1 and Th17 cells directly by enhancing mechanistic target of rapamycin complex 1(mTORC1)activation through the glutamine metabolism-dependent pathway.Reactive oxygen species(ROS)-induced activation of transforming growth factor-β(TGF-β)is also involved in fructose-induced Th17 cell generation.Moreover,metformin can reverse Th1 and Th17 cell generation induced by fructose by suppressing mTORC1 activation and reducing ROS-mediated TGF-βactivation.Finally,we identified metformin as an in vivo therapeutic drug for relieving high fructose consumption-induced T-cell inflammation and colitis aggravation.Our study revealed a previously unknown adverse effect of high fructose consumption in disrupting immune homeostasis and exacerbating IBD by directly promoting T-cell immunity,and showed metformin is a potential therapeutic for reversing the T cell immune imbalance caused by long-term high fructose consumption.展开更多
Objective:To evaluate the therapeutic potential of coumarin-loaded chitosan nanoparticles(CNNPs)in managing high-fructose diet-induced diabetes and associated complications.Methods:CNNPs were synthesized using an ioni...Objective:To evaluate the therapeutic potential of coumarin-loaded chitosan nanoparticles(CNNPs)in managing high-fructose diet-induced diabetes and associated complications.Methods:CNNPs were synthesized using an ionic gelation method with chitosan coating and characterized.Rats with a high-fructose diet-induced diabetes were treated with coumarin and CNNPs(30,70,and 100 mg/kg)for 6-12 weeks.Metabolic,inflammatory,oxidative stress,organ function,and cardiovascular parameters were assessed,and qRT-PCR studies were carried out for measuring the mRNA expression of glucose transporter-4(GLUT-4),sirtuin-1(SIRT1),pyrin domain containing-3(NLRP3),sterol regulatory element binding protein 1c(SREBP-1c),forkhead box O3(FOXO3),and endothelial nitric oxide synthase(eNOS)genes.Results:Nanoparticle characterization revealed a Z-average size of 510.8 nm with a+14 mV zeta potential.CNNP treatment was more effective than coumarin,normalizing glycemic markers(glycosylated hemoglobin,serum insulin,and fasting blood glucose),and lipid profiles(total cholesterol,low-density lipoprotein cholesterol,triglycerides,and high-density lipoprotein cholesterol).Significant improvements were also seen in adipokines(adiponectin,chemerin,and leptin),inflammatory cytokines(interleukin-6 and tumor necrosis factor-α),and oxidative stress markers(catalase,superoxide dismutase and malonaldehyde).In addition,both treatments significantly upregulated the gene expression of SIRT1,GLUT-4,and eNOS,and downregulated FOXO3,SREBP-1c,and NLRP3.Histopathological studies confirmed that CNNPs ameliorated diabetes-induced structural abnormalities in major organs.Conclusions:CNNPs demonstrate improved bioavailability and therapeutic efficacy,offering a promising strategy for managing high-fructose diet-induced metabolic dysfunction and its complications.展开更多
Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
The effects of berberine on the expression of hepatocyte nuclear factor-4α （HNF-4α） in liver of rats with fructose-induced insulin resistance and the molecular mechanism of berberine preventing insulin resistance ...The effects of berberine on the expression of hepatocyte nuclear factor-4α （HNF-4α） in liver of rats with fructose-induced insulin resistance and the molecular mechanism of berberine preventing insulin resistance were investigated. The experimental animals were divided into two groups of 16 animals each. The control group received a control routine diet containing 60% carbohydrate, and the study group a high-fructose diet containing 60% fructose as the sole source of carbohydrate. At the end of 6 weeks these were each subdivided into two groups. One was administered with berberine [187.5 mg/（kg·d） in 5 g/L carboxymethyl cellulose] by intragastric intubation and the other group was treated with a vehicle （5 g/L carboxymethyl cellulose）. The rats were fed on the same dietary regimen for the next 4 weeks. After the experimental period of 10 weeks, plasma glucose, insulin and triglyceride levels were measured. HOMA insulin resistance index （HOMA-IR） was assayed. Immunohistochemistry, semiquantitative RT-PCR and western blot were used to detect the expression of HNF-4α in liver. Compared with control diet, fructose feeding induced hyperinsulinemia, HOMA-IR and increased triglyceride （all P〈0.01）. Berberine prevented the rise in plasma insulin （P〈0.01）, HOMA-IR （P〈0.01） and triglyceride （P〈0.05） in the fructose-fed rats. No change in plasma glucose was seen among these groups. The mRNA and protein expression of HNF-4α was decreased in the fructose-fed rats, but berberine could promote its expression. It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4α in liver.展开更多
The use of artificial sweeteners is becoming increasingly common.High-fructose corn syrup(HFCS)and aspartame are the two most commonly used sweeteners.It is reported that their consumption was associated with the impa...The use of artificial sweeteners is becoming increasingly common.High-fructose corn syrup(HFCS)and aspartame are the two most commonly used sweeteners.It is reported that their consumption was associated with the impairment of cognitive function.However,the specific mechanism whereby HFCS and aspartame diets influence cognitive function is still unclear.Here,we administered 20%HFCS and 50 mg/kg aspartame in drinking water to establish a dietary intervention,and assessed mouse cognitive function using the novel object recognition(NOR)experiment.Results showed that the cognitive function of the mice declined in the NOR experiment.In order to clarify the molecular mechanisms,the Oxford Nanopore Technologies(ONT)platform was used to perform full-length RNA sequencing.As a result,662 long non-coding RNAs(lncRNAs)and 6895 alternative splicing(AS)events were identified,and the enrichment results of differentially expressed lncRNA target genes and AS genes suggested that the pathways related to cellular autophagy were enriched.The western blotting showed the PI3K/AKT/mTOR signaling pathway was activated,and the results of immunofluorescence also suggested that the HFCS and aspartame intake induced the accumulation of amyloid-βin the hippocampus.All in all,our study,starting from the dimensions of lncRNAs and AS,has deeply analyzed the potential mechanisms underlying the cognitive decline in mice caused by the intake of aspartame and HFCS,and put forward possible and novel insights.展开更多
High fructose corn syrup has been industrially produced by converting glucose to fructose by glucose isomerases,tetrameric metalloenzymes widely used in industrial biocatalysis.Advances in enzyme engineering and comme...High fructose corn syrup has been industrially produced by converting glucose to fructose by glucose isomerases,tetrameric metalloenzymes widely used in industrial biocatalysis.Advances in enzyme engineering and commercial production of glucose isomerase have paved the way to explore more efficient variants of these enzymes.The 5-hydroxymethylfurfural can be produced from high fructose corn syrup catalytic dehydration,and it can be further converted into various furanic compounds chemically or biologically for various industrial applications as a promising platform chemical.Although the chemical conversion of 5-hydroxymethylfurfural into furanic compounds has been extensively investigated in recent years,bioconversion has shown promise for its mild conditions due to the harsh chemical reaction conditions.This review discusses pro-tein engineering potential for improving glucose isomerase production and recent advancements in bioconversion of 5-hydroxymethylfurfural into value-added furanic derivatives.It suggests bi-ological strategies for the industrial transformation of 5-hydroxymethylfurfural.展开更多
Non-alcoholic steatohepatitis(NASH),a progressive form of NAFLD,is strongly associated with high-fructose diets.We investigated whether microbial fermentation could enhance the known hepatoprotective effects of extra ...Non-alcoholic steatohepatitis(NASH),a progressive form of NAFLD,is strongly associated with high-fructose diets.We investigated whether microbial fermentation could enhance the known hepatoprotective effects of extra virgin olive oil(EVOO)by modifying its bioactive compounds such as squalene and antioxidant potential.This study evaluated the effects of fermented EVOO on NASH induced by a high-fructose diet(HFrD)in rats.EVOO was optimized for fermentation using Yarrowia lipolytica,and the highest squalene level was selected based on GC-MS assessment.Male Sprague-Dawley rats were divided into four experimental groups(n=6 per group).One group was fed a balanced diet as the control group,while the other groups were placed on a high-fructose diet to induce steatohepatitis.Among these,one group served as the steatohepatitis group,while the remaining two groups received 10%EVOO and fermented EVOO in their diets,respectively,for six weeks.Liver function,serum glucose,insulin,lipid profiles,hepatic lipids,oxidative stress markers,interleukins-6 and IL-1β,as well as histopathological and immunohistochemical assessments,were conducted.Fermented EVOO,characterized by an increased squalene level,significantly improved liver function parameters(as indicated by lower ALT,AST,ALP,and bilirubin levels,p<0.05),markedly reduced insulin resistance(HOMA-IR,p<0.05),and significantly decreased hepatic lipid accumulation(total fat,cholesterol,and triglycerides in liver tissue,p<0.05)compared to the HFrD group.Additionally,significantly enhanced antioxidant markers(GSH:190.24±1.32 ng/mg;SOD:174.34±2.15 U/mg;catalase:10.56±0.86 ng/mg)compared to HFrD controls(GSH:81.29±2.01;SOD:71.02±1.57;catalase:6.77±0.14),while reducing oxidative stress(MDA:1.12±0.02 vs 2.21±0.02 nmol/mg)and inflammation markers(IL-6:6.24±0.98 vs 8.34±0.15 ng/g;IL-1β:7.84±0.99 vs 9.76±0.13 pg/g;all p<0.05).Histopathological examination revealed a significant reduction in collagen deposition and marked improvements in immunohistochemical changes.These findings suggest that fermented EVOO confers protective effects against high-fructose-induced hepatic steatohepatitis in rats.This highlights its potential as a dietary intervention for managing NASH.展开更多
The widely consumed high-fructose corn syrup(HFCS) has been linked to neurological disorders. In a recent article published in Nature, Wang et al. extend the harms of excessive fructose intake on neurodevelopment to t...The widely consumed high-fructose corn syrup(HFCS) has been linked to neurological disorders. In a recent article published in Nature, Wang et al. extend the harms of excessive fructose intake on neurodevelopment to the prenatal and lactation stages. They reveal that fructose uptake via GLUT5 reprograms microglial metabolism towards a low-ATP production state, suppressing microglial phagocytosis and impairing neurodevelopment.展开更多
Background and aims:Diet-induced obesity and metabolic syndrome can trigger the progression of fatty liver disease to non-alcoholic steatohepatitis and fibrosis,which is a major public health concern.Bile acids regula...Background and aims:Diet-induced obesity and metabolic syndrome can trigger the progression of fatty liver disease to non-alcoholic steatohepatitis and fibrosis,which is a major public health concern.Bile acids regulate metabolic homeostasis and inflammation in the liver and gut via the activation of nuclear farnesoid X receptor(Fxr)and the membrane receptor Takeda G protein-coupled receptor 5(Tgr5).Tgr5 is highly expressed in the gut and skeletal muscle,and in cholangiocytes and Kupffer cells of the liver.Tgr5 is implicated in the mediation of liver and gut inflammation,as well as the maintenance of energy homeostasis.Here,we used a high fat,high fructose,and high sucrose(HFS)diet to determine how bile acid signaling through Tgr5 may regulate metabolism during the progression from fatty liver to non-alcoholic steatohepatitis and fibrosis.Materials and methods:Female C57BL/6J control wild type(WT)and Tgr5 knockout(Tgr5^(-/-))mice were fed HFS(high fat(40%kcal),high fructose,and 20%sucrose water)diet for 20 weeks.Metabolic phe-notypes were characterized through examination of bile acid synthesis pathways,lipid and cholesterol metabolism pathways,and fibrosis and inflammation pathways.Results:Tgr5^(-/-)mice were more glucose intolerant when fed HFS diet,despite gaining the same amount of weight as WT mice.Tgr5^(-/-)mice accumulated significantly more hepatic cholesterol and triglycerides on HFS diet compared to WT mice,and gene expression of lipogenic genes was significantly upregulated.Hepatic cholesterol 7alpha-hydroxylase(Cyp7a1)gene expression was consistently elevated in Tgr5^(-/-)mice,while oxysterol 7alpha-hydroxylase(Cyp7b1),sterol 27-hydroxylase(Cyp27a1),Fxr,and small heterodimer partner(Shp)were downregulated by HFS diet.Surprisingly,hepatic inflammation and fibrosis were also significantly reduced in Tgr5^(-/-)mice fed HFS diet,which may be due to altered se-rotonin signaling in the liver.Conclusions:Tgr5^(-/-)mice may be protected from high fat,high sugar-induced hepatic inflammation and injury due to altered serotonin metabolism.展开更多
文摘As the consumption of fructose and saturated fatty acids(FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a mod-erate(10 weeks) and a prolonged(30 weeks) high fructose and saturated fatty acid(HFS) diet on plasma FA com-position in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to es-tablish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7)(decreased) and 20:4(n-6)(increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.
文摘Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.
基金financially supported by Ningxia Key Research and Development Program Grant(2024BBF02009).
文摘Insulin resistance is an increasingly severe public health issue worldwide,affecting millions and significantly raising the risk of diabetes and cardiovascular diseases.Despite this,current treatment options remain limited,which has heightened interest in exploring interventions based on natural compounds.This study investigates the potential of Lycium barbarum leaf flavonoids(LBLF)to improve insulin resistance induced by high fructose in mice,with a focus on the mechanisms related to blood glucose regulation and gut microbiota composition.Research results show that,compared to the high fructose model group,treatment with metformin hydrochloride and rutin reduced fasting blood glucose levels by 32.06%and 18.94%,respectively.LBLF treatment at various doses decreased fasting blood glucose levels by 12.29%,19.02%,and 32.98%,and insulin levels by 26.50%,11.04%,and 28.23%,respectively,demonstrating its effective ability to regulate blood glucose levels.It was also found that LBLF effectively regulated lipid disorders,significantly reduced oxidative stress in the liver,and protected liver function.Liver transcriptomic analysis suggests that LBLF may improve insulin resistance by regulating gene expression in the MAPK and retinol metabolism signaling pathways.Additionally,gut microbiota diversity analysis revealed that LBLF treatment reduced the Firmicutes/Bacteroidetes(F/B)ratio,which is asso-ciated with obesity and metabolic disorders,thereby optimizing the gut microbiota structure disrupted by high fructose intake.These results highlight the therapeutic potential of LBLF in managing insulin resistance and associated metabolic disorders,providing a theoretical basis for further research into its broader applications.
基金supported by the National Natural Science Foundation of China(NO.82171829)the Key Project of the Science and Technology Department of Sichuan Province(NO.2025YFHZ0205)+2 种基金the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(NO.ZYYC25010)supported by the Intramural Research Program of the U.S.National Institutes of Health(NIH)National Institute of Dental and Craniofacial Research(NIDCR).
文摘The intake of sugars,especially glucose and fructose,has significantly increased with the change of lifestyle.Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases.Fructose directly mediates innate immune responses;however,whether it can directly regulate T-cell immunity remains unknown.We show that high fructose consumption accelerates the development of inflammatory bowel disease(IBD)by promoting the generation of T helper 1(Th1)and T helper 17(Th17)cells.It was demonstrated that fructose promotes the differentiation of Th1 and Th17 cells directly by enhancing mechanistic target of rapamycin complex 1(mTORC1)activation through the glutamine metabolism-dependent pathway.Reactive oxygen species(ROS)-induced activation of transforming growth factor-β(TGF-β)is also involved in fructose-induced Th17 cell generation.Moreover,metformin can reverse Th1 and Th17 cell generation induced by fructose by suppressing mTORC1 activation and reducing ROS-mediated TGF-βactivation.Finally,we identified metformin as an in vivo therapeutic drug for relieving high fructose consumption-induced T-cell inflammation and colitis aggravation.Our study revealed a previously unknown adverse effect of high fructose consumption in disrupting immune homeostasis and exacerbating IBD by directly promoting T-cell immunity,and showed metformin is a potential therapeutic for reversing the T cell immune imbalance caused by long-term high fructose consumption.
基金This article is funded by HEC,520-163233-2AV6-09,Anam Iqbal.
文摘Objective:To evaluate the therapeutic potential of coumarin-loaded chitosan nanoparticles(CNNPs)in managing high-fructose diet-induced diabetes and associated complications.Methods:CNNPs were synthesized using an ionic gelation method with chitosan coating and characterized.Rats with a high-fructose diet-induced diabetes were treated with coumarin and CNNPs(30,70,and 100 mg/kg)for 6-12 weeks.Metabolic,inflammatory,oxidative stress,organ function,and cardiovascular parameters were assessed,and qRT-PCR studies were carried out for measuring the mRNA expression of glucose transporter-4(GLUT-4),sirtuin-1(SIRT1),pyrin domain containing-3(NLRP3),sterol regulatory element binding protein 1c(SREBP-1c),forkhead box O3(FOXO3),and endothelial nitric oxide synthase(eNOS)genes.Results:Nanoparticle characterization revealed a Z-average size of 510.8 nm with a+14 mV zeta potential.CNNP treatment was more effective than coumarin,normalizing glycemic markers(glycosylated hemoglobin,serum insulin,and fasting blood glucose),and lipid profiles(total cholesterol,low-density lipoprotein cholesterol,triglycerides,and high-density lipoprotein cholesterol).Significant improvements were also seen in adipokines(adiponectin,chemerin,and leptin),inflammatory cytokines(interleukin-6 and tumor necrosis factor-α),and oxidative stress markers(catalase,superoxide dismutase and malonaldehyde).In addition,both treatments significantly upregulated the gene expression of SIRT1,GLUT-4,and eNOS,and downregulated FOXO3,SREBP-1c,and NLRP3.Histopathological studies confirmed that CNNPs ameliorated diabetes-induced structural abnormalities in major organs.Conclusions:CNNPs demonstrate improved bioavailability and therapeutic efficacy,offering a promising strategy for managing high-fructose diet-induced metabolic dysfunction and its complications.
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
基金a grant from the National Natural Science Foundation of China (No. 30500685)
文摘The effects of berberine on the expression of hepatocyte nuclear factor-4α （HNF-4α） in liver of rats with fructose-induced insulin resistance and the molecular mechanism of berberine preventing insulin resistance were investigated. The experimental animals were divided into two groups of 16 animals each. The control group received a control routine diet containing 60% carbohydrate, and the study group a high-fructose diet containing 60% fructose as the sole source of carbohydrate. At the end of 6 weeks these were each subdivided into two groups. One was administered with berberine [187.5 mg/（kg·d） in 5 g/L carboxymethyl cellulose] by intragastric intubation and the other group was treated with a vehicle （5 g/L carboxymethyl cellulose）. The rats were fed on the same dietary regimen for the next 4 weeks. After the experimental period of 10 weeks, plasma glucose, insulin and triglyceride levels were measured. HOMA insulin resistance index （HOMA-IR） was assayed. Immunohistochemistry, semiquantitative RT-PCR and western blot were used to detect the expression of HNF-4α in liver. Compared with control diet, fructose feeding induced hyperinsulinemia, HOMA-IR and increased triglyceride （all P〈0.01）. Berberine prevented the rise in plasma insulin （P〈0.01）, HOMA-IR （P〈0.01） and triglyceride （P〈0.05） in the fructose-fed rats. No change in plasma glucose was seen among these groups. The mRNA and protein expression of HNF-4α was decreased in the fructose-fed rats, but berberine could promote its expression. It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4α in liver.
文摘The use of artificial sweeteners is becoming increasingly common.High-fructose corn syrup(HFCS)and aspartame are the two most commonly used sweeteners.It is reported that their consumption was associated with the impairment of cognitive function.However,the specific mechanism whereby HFCS and aspartame diets influence cognitive function is still unclear.Here,we administered 20%HFCS and 50 mg/kg aspartame in drinking water to establish a dietary intervention,and assessed mouse cognitive function using the novel object recognition(NOR)experiment.Results showed that the cognitive function of the mice declined in the NOR experiment.In order to clarify the molecular mechanisms,the Oxford Nanopore Technologies(ONT)platform was used to perform full-length RNA sequencing.As a result,662 long non-coding RNAs(lncRNAs)and 6895 alternative splicing(AS)events were identified,and the enrichment results of differentially expressed lncRNA target genes and AS genes suggested that the pathways related to cellular autophagy were enriched.The western blotting showed the PI3K/AKT/mTOR signaling pathway was activated,and the results of immunofluorescence also suggested that the HFCS and aspartame intake induced the accumulation of amyloid-βin the hippocampus.All in all,our study,starting from the dimensions of lncRNAs and AS,has deeply analyzed the potential mechanisms underlying the cognitive decline in mice caused by the intake of aspartame and HFCS,and put forward possible and novel insights.
基金supported by the Natural Sciences and Engineering Research Council of Canada(Grant number RGPIN-2017-05366)to WQ.
文摘High fructose corn syrup has been industrially produced by converting glucose to fructose by glucose isomerases,tetrameric metalloenzymes widely used in industrial biocatalysis.Advances in enzyme engineering and commercial production of glucose isomerase have paved the way to explore more efficient variants of these enzymes.The 5-hydroxymethylfurfural can be produced from high fructose corn syrup catalytic dehydration,and it can be further converted into various furanic compounds chemically or biologically for various industrial applications as a promising platform chemical.Although the chemical conversion of 5-hydroxymethylfurfural into furanic compounds has been extensively investigated in recent years,bioconversion has shown promise for its mild conditions due to the harsh chemical reaction conditions.This review discusses pro-tein engineering potential for improving glucose isomerase production and recent advancements in bioconversion of 5-hydroxymethylfurfural into value-added furanic derivatives.It suggests bi-ological strategies for the industrial transformation of 5-hydroxymethylfurfural.
文摘Non-alcoholic steatohepatitis(NASH),a progressive form of NAFLD,is strongly associated with high-fructose diets.We investigated whether microbial fermentation could enhance the known hepatoprotective effects of extra virgin olive oil(EVOO)by modifying its bioactive compounds such as squalene and antioxidant potential.This study evaluated the effects of fermented EVOO on NASH induced by a high-fructose diet(HFrD)in rats.EVOO was optimized for fermentation using Yarrowia lipolytica,and the highest squalene level was selected based on GC-MS assessment.Male Sprague-Dawley rats were divided into four experimental groups(n=6 per group).One group was fed a balanced diet as the control group,while the other groups were placed on a high-fructose diet to induce steatohepatitis.Among these,one group served as the steatohepatitis group,while the remaining two groups received 10%EVOO and fermented EVOO in their diets,respectively,for six weeks.Liver function,serum glucose,insulin,lipid profiles,hepatic lipids,oxidative stress markers,interleukins-6 and IL-1β,as well as histopathological and immunohistochemical assessments,were conducted.Fermented EVOO,characterized by an increased squalene level,significantly improved liver function parameters(as indicated by lower ALT,AST,ALP,and bilirubin levels,p<0.05),markedly reduced insulin resistance(HOMA-IR,p<0.05),and significantly decreased hepatic lipid accumulation(total fat,cholesterol,and triglycerides in liver tissue,p<0.05)compared to the HFrD group.Additionally,significantly enhanced antioxidant markers(GSH:190.24±1.32 ng/mg;SOD:174.34±2.15 U/mg;catalase:10.56±0.86 ng/mg)compared to HFrD controls(GSH:81.29±2.01;SOD:71.02±1.57;catalase:6.77±0.14),while reducing oxidative stress(MDA:1.12±0.02 vs 2.21±0.02 nmol/mg)and inflammation markers(IL-6:6.24±0.98 vs 8.34±0.15 ng/g;IL-1β:7.84±0.99 vs 9.76±0.13 pg/g;all p<0.05).Histopathological examination revealed a significant reduction in collagen deposition and marked improvements in immunohistochemical changes.These findings suggest that fermented EVOO confers protective effects against high-fructose-induced hepatic steatohepatitis in rats.This highlights its potential as a dietary intervention for managing NASH.
文摘The widely consumed high-fructose corn syrup(HFCS) has been linked to neurological disorders. In a recent article published in Nature, Wang et al. extend the harms of excessive fructose intake on neurodevelopment to the prenatal and lactation stages. They reveal that fructose uptake via GLUT5 reprograms microglial metabolism towards a low-ATP production state, suppressing microglial phagocytosis and impairing neurodevelopment.
基金This work was supported by the USA National Institutes of Health(NIH)(AA015951,DK044442,and DK058379).
文摘Background and aims:Diet-induced obesity and metabolic syndrome can trigger the progression of fatty liver disease to non-alcoholic steatohepatitis and fibrosis,which is a major public health concern.Bile acids regulate metabolic homeostasis and inflammation in the liver and gut via the activation of nuclear farnesoid X receptor(Fxr)and the membrane receptor Takeda G protein-coupled receptor 5(Tgr5).Tgr5 is highly expressed in the gut and skeletal muscle,and in cholangiocytes and Kupffer cells of the liver.Tgr5 is implicated in the mediation of liver and gut inflammation,as well as the maintenance of energy homeostasis.Here,we used a high fat,high fructose,and high sucrose(HFS)diet to determine how bile acid signaling through Tgr5 may regulate metabolism during the progression from fatty liver to non-alcoholic steatohepatitis and fibrosis.Materials and methods:Female C57BL/6J control wild type(WT)and Tgr5 knockout(Tgr5^(-/-))mice were fed HFS(high fat(40%kcal),high fructose,and 20%sucrose water)diet for 20 weeks.Metabolic phe-notypes were characterized through examination of bile acid synthesis pathways,lipid and cholesterol metabolism pathways,and fibrosis and inflammation pathways.Results:Tgr5^(-/-)mice were more glucose intolerant when fed HFS diet,despite gaining the same amount of weight as WT mice.Tgr5^(-/-)mice accumulated significantly more hepatic cholesterol and triglycerides on HFS diet compared to WT mice,and gene expression of lipogenic genes was significantly upregulated.Hepatic cholesterol 7alpha-hydroxylase(Cyp7a1)gene expression was consistently elevated in Tgr5^(-/-)mice,while oxysterol 7alpha-hydroxylase(Cyp7b1),sterol 27-hydroxylase(Cyp27a1),Fxr,and small heterodimer partner(Shp)were downregulated by HFS diet.Surprisingly,hepatic inflammation and fibrosis were also significantly reduced in Tgr5^(-/-)mice fed HFS diet,which may be due to altered se-rotonin signaling in the liver.Conclusions:Tgr5^(-/-)mice may be protected from high fat,high sugar-induced hepatic inflammation and injury due to altered serotonin metabolism.
