AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding ei...AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.展开更多
Background Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examine...Background Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the forma tion of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr ) mice. Methods Forty-eight 7-week-old LDLr/ mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P 〈 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P 〈 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLrmice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.展开更多
AIM: To analyze the microbiota shift in the dista esophagus of Sprague-Dawley rats fed a high-fat diet. METHODS: Twenty Sprague-Dawley rats were divided into high-fat diet and normal control groups of 10 rats each. ...AIM: To analyze the microbiota shift in the dista esophagus of Sprague-Dawley rats fed a high-fat diet. METHODS: Twenty Sprague-Dawley rats were divided into high-fat diet and normal control groups of 10 rats each. The composition of microbiota in the mucosa from the distal esophagus was analyzed based on se- lective culture. A variety of Lactobacillus species were identified by molecular biological techniques. Bacterial DNA from Lactobacillus colonies was extracted, and 165 rDNA was amplified by PCR using bacterial uni- versal primers. The amplified 16S rDNA products were separated by denaturing gradient gel electrophoresis (DGGE). Every single band was purified from the gel and sent to be sequenced. RESULTS: Based on mucosal bacterial culturing in the distal esophagus, Staphylococcus aureus was absent, and total anaerobes and Lactobacillus species were de- creased significantly in the high-fat diet group compared with the normal control group (P 〈 0.01). Detailed DGGE analysis on the composition of Lactobacillus species in the distal esophagus revealed that Lactobacillus crispa- tus, Lactobacillus gasseri (L. gasser/] and Lactobacillus reuteri (L. reuterl] comprised the Lactobacillus species in the high-fat diet group, while the composition of Lactobacillus species in the normal control group consisted of L. gasseri, Lactobacillus jensenii and L. reuteri. CONCLUSION: High-fat diet led to a mucosal micro- flora shift in the distal esophagus in rats, especially the composition of Lactobacillus species.展开更多
Background: Physical activity(PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat highcarbohydrate(HFHC) diet influences the effect of different intensities of PA on ...Background: Physical activity(PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat highcarbohydrate(HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training(LIT), and high-intensity interval training(HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult rats.Methods: Twelve-week-old Wistar rats were randomly allocated to 4 groups(12 rats/group): control(CTL), sedentary(SED), LIT, and HIIT.Biometric indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA interventions.Results: The SED group had slower cardiac conduction(p = 0.0426) and greater thoracic aortic contractile responses(p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group(p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group(both p < 0.05). The LIT and HIIT groups had lower visceral(p = 0.0057 for LIT, p = 0.0120 for HIIT)and epididymal fat(p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL group.Conclusion: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation,mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.展开更多
To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies us...To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.RESULTSUpregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson’s trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models.CONCLUSIONThese data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.展开更多
The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot(Scophthalmus maximus) reared at five salinities(12,18,24,30,and 36).The fish were fed three isoca...The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot(Scophthalmus maximus) reared at five salinities(12,18,24,30,and 36).The fish were fed three isocaloric and isolipidic diets for 60 days.The results show that specific growth rate(SGR)and feed conversion efficiency(FCE) were higher in fish reared at salinities of 18 and 36,but lower at 12.Fish fed with diet C25P40(25%carbohydrate and 40%protein) had lower SGR and FCE values compared with those fed with the C5P52(5%carbohydrate and 52%protein) and C15P46(15%carbohydrate and 46%protein) diets;however,there was no statistical difference between diet C5P52 and C15P46.SGR and FCE values were unaffected by diet composition in fish reared at salinity 36.Hepatic lipogenic enzyme activities were higher in fish reared at 18 and 36,but lower at 12,while glucokinase(GK) activity was higher in fish reared at 12,and lower at 18 and 36.Dietary starch enhanced GK activity while depressing lipogenic enzyme activity.However,lipogenic enzyme activity increased with increasing dietary starch in fish reared at 36.It is recommended that salinity should be maintained > 12 in the farming of juvenile turbot.In addition,an increase in gelatinized starch from 5%to 15%could spare 6%dietary protein in fish reared at salinities of 18-30,while higher salinity(36) could improve dietary carbohydrate use and enhance the protein-sparing effect,which is linked with the induction of lipogenic capacities.展开更多
With the social and economic developing, people' s living standards continue to improve, and diet structure has undergone significant changes. Meat, fish, dairy products, snack and foods of high fat, and high protein...With the social and economic developing, people' s living standards continue to improve, and diet structure has undergone significant changes. Meat, fish, dairy products, snack and foods of high fat, and high protein proportion increase significantly. Malnutrition and low birth weight situation caused due to lack of food have gradually reduced. Irrational diet causes relative excess nutrients and new malnutrition, and thus lead to the proportion of people of obesity, hypertension, hyperlipidemia, coronary heart disease and diabetes has increased year by year. People regard these diseases as "diseases of affluence ", where obesity is the most common but the most easily overlooked. In recent years, with the release of the results and physical research concerned about scholars, obesity has attracted people' s attention.展开更多
Because of their physiological similarity to humans, pigs provide an excellent model for the study of obesity. This study evaluated diet-induced adiposity in genetically lean pigs and found that body weight and energy...Because of their physiological similarity to humans, pigs provide an excellent model for the study of obesity. This study evaluated diet-induced adiposity in genetically lean pigs and found that body weight and energy intake did not differ between controls and pigs fed the high-fat (HF) diet for three months. However, fat mass percentage, adi- pocyte size, concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), insulin, and leptin in plasma were significantly higher in HF pigs than in controls. The HF diet increased the expression in backfat tissue of genes responsible for cholesterol synthesis such as Insig-1 and Insig-2. Lipid metabolism-related genes including sterol regulatory element binding protein lc (SREBP-lc), fatty acid synthase 1 (FASN1), diacylglycerol O-acyltransferase 2 (DGAT2), and fatty acid binding protein 4 (FABP4) were significantly up-regulated in backfat tissue, while the expression of proliferator-activated receptor-α(PPAR-α) and carnitine palmitoyl transferase 2 (CPT2), both involved in fatty acid oxidation, was reduced. In liver tissue, HF feeding significantly elevated the expression of SREBP-lc, FASN1, DGAT2, and hepatocyte nuclear factor-4α (HNF-4α) mRNAs. Microarray analysis further showed that the HF diet had a significant effect on the expression of 576 genes. Among these, 108 genes were related to 21 pathways, with 20 genes involved in adiposity deposition and 26 related to immune response. Our results suggest that an HF diet can induce genetically lean pigs into obesity with body fat mass expansion and adipose-related inflammation.展开更多
Abnormal hepatic lipid metabolism is a key component of fatty liver development with excess fat deposition in the liver through steatosis. Cystathionine gamma-lyase (CSE) is one of the enzymes that catalyze hydrogen...Abnormal hepatic lipid metabolism is a key component of fatty liver development with excess fat deposition in the liver through steatosis. Cystathionine gamma-lyase (CSE) is one of the enzymes that catalyze hydrogen sulfide (HAS) production in the liver. The aim of the present study was to investigate the role of CSE/H2S in hepatic regulation of cholesterol and fatty acid metabolism. Wild-type (WT) and CSE knockout (CSE-KO) mice fed with high-fat diet (HFD) were analyzed for liver morphological and biochemical changes. HFD feeding of CSE-KO mice, not WT mice, markedly increased cholesterol levels in plasma and livers, and the sizes of the liver and gall bladder. Typical histological and biochemical changes of fatty liver disease were found in CSE-KO mice with damaged liver functions. The levels of plasma and liver triglyceride were significantly lower in HFD-fed CSE-KO mice than in HFD-fed WT mice. Moreover, the expression of nuclear receptors transcriptional factors, especially LXRα, in the liver was decreased in both control diet-or HFD-fed CSE-KO mice. Decreased expression of CYP7A1, an LXRα targeted gene, halted catabolism of cholesterol into bile and subsequently led to cholesterol accumulation in the liver and gall bladder. Since deficiency in CSE/H2S pathway results in high susceptibility to HFD- induced fatty liver, targeting at CSE/H2S pathway in the liver may represent a novel strategy against the development of fatty liver damage.展开更多
基金Supported by The Fok Ying-Tong Education Foundation, China, No. 114036Leading Academic Discipline Project of Shanghai Municipal Education Commission, No. J50307State Administration of Traditional Chinese Medicine
文摘AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.
文摘Background Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the forma tion of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr ) mice. Methods Forty-eight 7-week-old LDLr/ mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P 〈 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P 〈 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLrmice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.
文摘AIM: To analyze the microbiota shift in the dista esophagus of Sprague-Dawley rats fed a high-fat diet. METHODS: Twenty Sprague-Dawley rats were divided into high-fat diet and normal control groups of 10 rats each. The composition of microbiota in the mucosa from the distal esophagus was analyzed based on se- lective culture. A variety of Lactobacillus species were identified by molecular biological techniques. Bacterial DNA from Lactobacillus colonies was extracted, and 165 rDNA was amplified by PCR using bacterial uni- versal primers. The amplified 16S rDNA products were separated by denaturing gradient gel electrophoresis (DGGE). Every single band was purified from the gel and sent to be sequenced. RESULTS: Based on mucosal bacterial culturing in the distal esophagus, Staphylococcus aureus was absent, and total anaerobes and Lactobacillus species were de- creased significantly in the high-fat diet group compared with the normal control group (P 〈 0.01). Detailed DGGE analysis on the composition of Lactobacillus species in the distal esophagus revealed that Lactobacillus crispa- tus, Lactobacillus gasseri (L. gasser/] and Lactobacillus reuteri (L. reuterl] comprised the Lactobacillus species in the high-fat diet group, while the composition of Lactobacillus species in the normal control group consisted of L. gasseri, Lactobacillus jensenii and L. reuteri. CONCLUSION: High-fat diet led to a mucosal micro- flora shift in the distal esophagus in rats, especially the composition of Lactobacillus species.
基金supported by the Strategic Research Scholarship grant from Central Queensland University (CQU)in part supported by CQU Health CRNsupported by a Future Leader Fellowship (ID 100029) from the National Heart Foundation of Australia
文摘Background: Physical activity(PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat highcarbohydrate(HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training(LIT), and high-intensity interval training(HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult rats.Methods: Twelve-week-old Wistar rats were randomly allocated to 4 groups(12 rats/group): control(CTL), sedentary(SED), LIT, and HIIT.Biometric indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA interventions.Results: The SED group had slower cardiac conduction(p = 0.0426) and greater thoracic aortic contractile responses(p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group(p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group(both p < 0.05). The LIT and HIIT groups had lower visceral(p = 0.0057 for LIT, p = 0.0120 for HIIT)and epididymal fat(p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL group.Conclusion: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation,mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.
文摘To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.RESULTSUpregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson’s trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models.CONCLUSIONThese data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.
基金Supported by the Special Fund of Chinese Ministry of Agriculture for Modern Agriculture Industry System Construction(No.CARS-50)
文摘The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot(Scophthalmus maximus) reared at five salinities(12,18,24,30,and 36).The fish were fed three isocaloric and isolipidic diets for 60 days.The results show that specific growth rate(SGR)and feed conversion efficiency(FCE) were higher in fish reared at salinities of 18 and 36,but lower at 12.Fish fed with diet C25P40(25%carbohydrate and 40%protein) had lower SGR and FCE values compared with those fed with the C5P52(5%carbohydrate and 52%protein) and C15P46(15%carbohydrate and 46%protein) diets;however,there was no statistical difference between diet C5P52 and C15P46.SGR and FCE values were unaffected by diet composition in fish reared at salinity 36.Hepatic lipogenic enzyme activities were higher in fish reared at 18 and 36,but lower at 12,while glucokinase(GK) activity was higher in fish reared at 12,and lower at 18 and 36.Dietary starch enhanced GK activity while depressing lipogenic enzyme activity.However,lipogenic enzyme activity increased with increasing dietary starch in fish reared at 36.It is recommended that salinity should be maintained > 12 in the farming of juvenile turbot.In addition,an increase in gelatinized starch from 5%to 15%could spare 6%dietary protein in fish reared at salinities of 18-30,while higher salinity(36) could improve dietary carbohydrate use and enhance the protein-sparing effect,which is linked with the induction of lipogenic capacities.
文摘With the social and economic developing, people' s living standards continue to improve, and diet structure has undergone significant changes. Meat, fish, dairy products, snack and foods of high fat, and high protein proportion increase significantly. Malnutrition and low birth weight situation caused due to lack of food have gradually reduced. Irrational diet causes relative excess nutrients and new malnutrition, and thus lead to the proportion of people of obesity, hypertension, hyperlipidemia, coronary heart disease and diabetes has increased year by year. People regard these diseases as "diseases of affluence ", where obesity is the most common but the most easily overlooked. In recent years, with the release of the results and physical research concerned about scholars, obesity has attracted people' s attention.
基金Project supported by the National Key Research and Development Program of China(Nos.2018YFD0500400 and 2018YFD0501100)the National Basic Research Program(973)of China(No.2013CB127304)+1 种基金the China Agriculture Research System(No.CARS-36)and the National Natural Science Foundation of China(No.31402086)
文摘Because of their physiological similarity to humans, pigs provide an excellent model for the study of obesity. This study evaluated diet-induced adiposity in genetically lean pigs and found that body weight and energy intake did not differ between controls and pigs fed the high-fat (HF) diet for three months. However, fat mass percentage, adi- pocyte size, concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), insulin, and leptin in plasma were significantly higher in HF pigs than in controls. The HF diet increased the expression in backfat tissue of genes responsible for cholesterol synthesis such as Insig-1 and Insig-2. Lipid metabolism-related genes including sterol regulatory element binding protein lc (SREBP-lc), fatty acid synthase 1 (FASN1), diacylglycerol O-acyltransferase 2 (DGAT2), and fatty acid binding protein 4 (FABP4) were significantly up-regulated in backfat tissue, while the expression of proliferator-activated receptor-α(PPAR-α) and carnitine palmitoyl transferase 2 (CPT2), both involved in fatty acid oxidation, was reduced. In liver tissue, HF feeding significantly elevated the expression of SREBP-lc, FASN1, DGAT2, and hepatocyte nuclear factor-4α (HNF-4α) mRNAs. Microarray analysis further showed that the HF diet had a significant effect on the expression of 576 genes. Among these, 108 genes were related to 21 pathways, with 20 genes involved in adiposity deposition and 26 related to immune response. Our results suggest that an HF diet can induce genetically lean pigs into obesity with body fat mass expansion and adipose-related inflammation.
基金supported by an operating grant to RW from Canadian Institutes of Health Researcha Mid-career Investigator Award to LW from the Heart and Stroke Foundation of Ontario, Canada
文摘Abnormal hepatic lipid metabolism is a key component of fatty liver development with excess fat deposition in the liver through steatosis. Cystathionine gamma-lyase (CSE) is one of the enzymes that catalyze hydrogen sulfide (HAS) production in the liver. The aim of the present study was to investigate the role of CSE/H2S in hepatic regulation of cholesterol and fatty acid metabolism. Wild-type (WT) and CSE knockout (CSE-KO) mice fed with high-fat diet (HFD) were analyzed for liver morphological and biochemical changes. HFD feeding of CSE-KO mice, not WT mice, markedly increased cholesterol levels in plasma and livers, and the sizes of the liver and gall bladder. Typical histological and biochemical changes of fatty liver disease were found in CSE-KO mice with damaged liver functions. The levels of plasma and liver triglyceride were significantly lower in HFD-fed CSE-KO mice than in HFD-fed WT mice. Moreover, the expression of nuclear receptors transcriptional factors, especially LXRα, in the liver was decreased in both control diet-or HFD-fed CSE-KO mice. Decreased expression of CYP7A1, an LXRα targeted gene, halted catabolism of cholesterol into bile and subsequently led to cholesterol accumulation in the liver and gall bladder. Since deficiency in CSE/H2S pathway results in high susceptibility to HFD- induced fatty liver, targeting at CSE/H2S pathway in the liver may represent a novel strategy against the development of fatty liver damage.