AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided in...AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.展开更多
BACKGROUND Obesity is a disease state with serious adverse metabolic complications,including glucose intolerance and type 2 diabetes that currently has no cure.Identifying and understanding roles of various modulators...BACKGROUND Obesity is a disease state with serious adverse metabolic complications,including glucose intolerance and type 2 diabetes that currently has no cure.Identifying and understanding roles of various modulators of body composition and glucose homeostasis is required for developing effective cures.Syndecan-1(Sdc1) is a member of the heparan sulfate proteoglycan family that has mainly been investigated for its role in regulating proliferation and survival of epithelia and tumor cells,but little is known about its roles in regulating obesity and glucose homeostasis.AIM To examine the role of Sdc1 in regulating body fat and glucose metabolism.METHODS We used female wild type and Sdc1 knockout(Sdc1 KO) mice on BALB/c background and multiple methods.Metabolic measurements(rates of oxygen consumption,carbon dioxide production,respiratory exchange ratio and energy expenditure) were performed using an open-flow indirect calorimeter with additional features to measure food intake and physical activity.Glucose intolerance and insulin resistance were measured by established tolerance test methods.RESULTS Although our primary goal was to investigate the effects of Sdc1 deficiency on body fat and glucose homeostasis,we uncovered that Sdc1 regulates multiple metabolic parameters.Sdc1 KO mice have reduced body weight due to significant decreases in fat and lean masses under both chow and high fat diet conditions.The reduced body weight was not due to changes in food intakes,but Sdc1 KO mice exhibited altered feeding behavior as they ate more during the dark phase and less during the light phase than wild type mice.In addition,Sdc1 KO mice suffered from high rate of energy expenditure,glucose intolerance and insulin resistance.CONCLUSION These results reveal critical multisystem and opposing roles for Sdc1 in regulating normal energy balance and glucose homeostasis.The results will have important implications for targeting Sdc1 to modulate metabolic parameters.Finally,we offer a novel hypothesis that could reconcile the opposing roles associated with Sdc1 deficiency.展开更多
目的探究降浊合剂浓缩液对肥胖大鼠体质量、糖脂指标的影响。方法将30只SD大鼠随机分为正常组、模型组和给药组,每组各10只。正常组大鼠给予普通饲料足量喂养+生理盐水灌胃,模型组大鼠给予高脂饲料足量喂养+生理盐水灌胃,给药组大鼠给...目的探究降浊合剂浓缩液对肥胖大鼠体质量、糖脂指标的影响。方法将30只SD大鼠随机分为正常组、模型组和给药组,每组各10只。正常组大鼠给予普通饲料足量喂养+生理盐水灌胃,模型组大鼠给予高脂饲料足量喂养+生理盐水灌胃,给药组大鼠给予高脂饲料足量喂养+降浊合剂浓缩液灌胃。干预8周后,观察各组大鼠的大体情况和体质量变化,采用苏木精–伊红染色(hematoxylin and eosin staining,HE染色)观察脂肪细胞的病理变化,比较血糖(glucose,GLU)、总胆固醇(totalcholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白胆固醇(lowdensity lipoprotein-cholesterol,LDL-C)水平。结果干预后,给药组大鼠的精神状态、皮毛光泽度显著改善,且干预7~8周的体质量显著低于模型组(P<0.05);HE染色观察显示,给药组大鼠的白色、棕色脂肪细胞体积接近正常组;给药组大鼠的TG显著低于模型组(P<0.05),GLU、TC、LDL-C水平略低于模型组,但比较无统计学意义(P>0.05)。结论降浊合剂浓缩液能够改善肥胖大鼠的体质量和皮毛光泽度,缓解脂肪组织变性,降低糖脂指标。展开更多
To study the high-fat-diet induced rat obesity and the of fect of endurance training on the body fat content of obese rats, we randomly divided 66 male weanling SD rats into control(16 rats) and high fat diet group(50...To study the high-fat-diet induced rat obesity and the of fect of endurance training on the body fat content of obese rats, we randomly divided 66 male weanling SD rats into control(16 rats) and high fat diet group(50 rats). After 10 weeks, we chose diet-induced obese rats(DIO, 26 rats) and divided them into endurance training group(DIO-T, 8 rats) and DIO groups(DIO, 18 rats) randomly. Aner 8 weeks, endurance training, all rats were killed. The results showed that nosignificant difference was found between groups in body weight, the feed efficiency of DIO groups was higher than control groups, tke carass fat con tent of DIO-T group was significantlylower than DIO group, and plasma insulin concentration of DIO group was higher than control and DIO-T groups. It was suggested that rats’ obesity was induced obesity by high fat diet, dietary obesity had relation to higher eding efficiency and hyperinsulinemia. Endurance training can effectively reduce the body fat content of high-fat-diet induced obese rats by improving its hyper-insulinemia. Plasma TCH and TG of all rats had no significant difference.展开更多
选用750尾初体质量为（114.2±6.5） g的大菱鲆（Scophthalmus maximus L.）,随机分成5组,每组3个重复,每重复50尾鱼,分别投喂在高脂基础饲料中添加0（D-0）、120（D-120）、240（D-240）、480（D-480）和960 mg/kg （D-960）的DL-...选用750尾初体质量为（114.2±6.5） g的大菱鲆（Scophthalmus maximus L.）,随机分成5组,每组3个重复,每重复50尾鱼,分别投喂在高脂基础饲料中添加0（D-0）、120（D-120）、240（D-240）、480（D-480）和960 mg/kg （D-960）的DL-α-生育酚醋酸酯5种试验饲料养殖110 d,考察维生素E（VE）对高脂饲料养殖大菱鲆生长、脂类代谢和抗氧化性能的影响。结果表明, D-240组大菱鲆末均质量最高,且显著高于D-0组（对照组）（P〈0.05）,与其他组差异不显著（P〉0.05）； D-120组和D-240组饲料系数显著低于D-0组（P〈0.05）,但蛋白质效率显著高于D-0组（P〈0.05）。D-0组和D-960组血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇和谷丙转氨酶显著高于其他各组（P〈0.05）,而D-0组和D-960组高密度脂蛋白胆固醇则显著低于其他各组（P〈0.05）；随着饲料VE添加水平的增加,大菱鲆肝脂蛋白脂酶（LPL）活性有降低的趋势；脂肪酸合成酶（FAS）活性,有先增加后降低的趋势。大菱鲆肝总抗氧化酶、超级氧化歧化酶和过氧化氢酶活性,均随VE添加水平的升高有先升高后下降的趋势,而丙二醛含量的变化趋势则相反；随着饲料 VE 水平的增加,大菱鲆肝 VE 积累量有显著升高的趋势（P〈0.05）,肌肉 VE 的积累量先升高后恒定在一个水平。综上所述,在高脂饲料中添加适量的维生素E （有效含量124~243 mg/kg）能改善大菱鲆生长性能、饲料利用效率、鱼肝体指数、脏体指数,调节和改善血脂代谢,可调控机体脂肪代谢酶活性,提高机体组织VE积累量和肝抗氧化功能。本研究旨在通过考察添加不同水平的 VE 对高脂胁迫下大菱鲆生长、脂类代谢酶、抗氧化能力的影响,为VE在高脂胁迫下的合理使用及以VE营养调控鱼类脂肪代谢和改善抗氧化功能提供参考依据。展开更多
基金Supported by National Key R&D Program of China No.2017YFC0908900National Key Basic Research Project,No.2012CB517501National Natural Science Foundation of China,No.81470840 and No.81600464
文摘AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.
文摘BACKGROUND Obesity is a disease state with serious adverse metabolic complications,including glucose intolerance and type 2 diabetes that currently has no cure.Identifying and understanding roles of various modulators of body composition and glucose homeostasis is required for developing effective cures.Syndecan-1(Sdc1) is a member of the heparan sulfate proteoglycan family that has mainly been investigated for its role in regulating proliferation and survival of epithelia and tumor cells,but little is known about its roles in regulating obesity and glucose homeostasis.AIM To examine the role of Sdc1 in regulating body fat and glucose metabolism.METHODS We used female wild type and Sdc1 knockout(Sdc1 KO) mice on BALB/c background and multiple methods.Metabolic measurements(rates of oxygen consumption,carbon dioxide production,respiratory exchange ratio and energy expenditure) were performed using an open-flow indirect calorimeter with additional features to measure food intake and physical activity.Glucose intolerance and insulin resistance were measured by established tolerance test methods.RESULTS Although our primary goal was to investigate the effects of Sdc1 deficiency on body fat and glucose homeostasis,we uncovered that Sdc1 regulates multiple metabolic parameters.Sdc1 KO mice have reduced body weight due to significant decreases in fat and lean masses under both chow and high fat diet conditions.The reduced body weight was not due to changes in food intakes,but Sdc1 KO mice exhibited altered feeding behavior as they ate more during the dark phase and less during the light phase than wild type mice.In addition,Sdc1 KO mice suffered from high rate of energy expenditure,glucose intolerance and insulin resistance.CONCLUSION These results reveal critical multisystem and opposing roles for Sdc1 in regulating normal energy balance and glucose homeostasis.The results will have important implications for targeting Sdc1 to modulate metabolic parameters.Finally,we offer a novel hypothesis that could reconcile the opposing roles associated with Sdc1 deficiency.
文摘目的探究降浊合剂浓缩液对肥胖大鼠体质量、糖脂指标的影响。方法将30只SD大鼠随机分为正常组、模型组和给药组,每组各10只。正常组大鼠给予普通饲料足量喂养+生理盐水灌胃,模型组大鼠给予高脂饲料足量喂养+生理盐水灌胃,给药组大鼠给予高脂饲料足量喂养+降浊合剂浓缩液灌胃。干预8周后,观察各组大鼠的大体情况和体质量变化,采用苏木精–伊红染色(hematoxylin and eosin staining,HE染色)观察脂肪细胞的病理变化,比较血糖(glucose,GLU)、总胆固醇(totalcholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白胆固醇(lowdensity lipoprotein-cholesterol,LDL-C)水平。结果干预后,给药组大鼠的精神状态、皮毛光泽度显著改善,且干预7~8周的体质量显著低于模型组(P<0.05);HE染色观察显示,给药组大鼠的白色、棕色脂肪细胞体积接近正常组;给药组大鼠的TG显著低于模型组(P<0.05),GLU、TC、LDL-C水平略低于模型组,但比较无统计学意义(P>0.05)。结论降浊合剂浓缩液能够改善肥胖大鼠的体质量和皮毛光泽度,缓解脂肪组织变性,降低糖脂指标。
文摘To study the high-fat-diet induced rat obesity and the of fect of endurance training on the body fat content of obese rats, we randomly divided 66 male weanling SD rats into control(16 rats) and high fat diet group(50 rats). After 10 weeks, we chose diet-induced obese rats(DIO, 26 rats) and divided them into endurance training group(DIO-T, 8 rats) and DIO groups(DIO, 18 rats) randomly. Aner 8 weeks, endurance training, all rats were killed. The results showed that nosignificant difference was found between groups in body weight, the feed efficiency of DIO groups was higher than control groups, tke carass fat con tent of DIO-T group was significantlylower than DIO group, and plasma insulin concentration of DIO group was higher than control and DIO-T groups. It was suggested that rats’ obesity was induced obesity by high fat diet, dietary obesity had relation to higher eding efficiency and hyperinsulinemia. Endurance training can effectively reduce the body fat content of high-fat-diet induced obese rats by improving its hyper-insulinemia. Plasma TCH and TG of all rats had no significant difference.
文摘选用750尾初体质量为（114.2±6.5） g的大菱鲆（Scophthalmus maximus L.）,随机分成5组,每组3个重复,每重复50尾鱼,分别投喂在高脂基础饲料中添加0（D-0）、120（D-120）、240（D-240）、480（D-480）和960 mg/kg （D-960）的DL-α-生育酚醋酸酯5种试验饲料养殖110 d,考察维生素E（VE）对高脂饲料养殖大菱鲆生长、脂类代谢和抗氧化性能的影响。结果表明, D-240组大菱鲆末均质量最高,且显著高于D-0组（对照组）（P〈0.05）,与其他组差异不显著（P〉0.05）； D-120组和D-240组饲料系数显著低于D-0组（P〈0.05）,但蛋白质效率显著高于D-0组（P〈0.05）。D-0组和D-960组血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇和谷丙转氨酶显著高于其他各组（P〈0.05）,而D-0组和D-960组高密度脂蛋白胆固醇则显著低于其他各组（P〈0.05）；随着饲料VE添加水平的增加,大菱鲆肝脂蛋白脂酶（LPL）活性有降低的趋势；脂肪酸合成酶（FAS）活性,有先增加后降低的趋势。大菱鲆肝总抗氧化酶、超级氧化歧化酶和过氧化氢酶活性,均随VE添加水平的升高有先升高后下降的趋势,而丙二醛含量的变化趋势则相反；随着饲料 VE 水平的增加,大菱鲆肝 VE 积累量有显著升高的趋势（P〈0.05）,肌肉 VE 的积累量先升高后恒定在一个水平。综上所述,在高脂饲料中添加适量的维生素E （有效含量124~243 mg/kg）能改善大菱鲆生长性能、饲料利用效率、鱼肝体指数、脏体指数,调节和改善血脂代谢,可调控机体脂肪代谢酶活性,提高机体组织VE积累量和肝抗氧化功能。本研究旨在通过考察添加不同水平的 VE 对高脂胁迫下大菱鲆生长、脂类代谢酶、抗氧化能力的影响,为VE在高脂胁迫下的合理使用及以VE营养调控鱼类脂肪代谢和改善抗氧化功能提供参考依据。
