The intracellular lipids in muscle cells of farm animals play a crucial role in determining the overall intramuscular fat(IMF)content,which has a positive impact on meat quality.However,the mechanisms underlying the d...The intracellular lipids in muscle cells of farm animals play a crucial role in determining the overall intramuscular fat(IMF)content,which has a positive impact on meat quality.However,the mechanisms underlying the deposition of lipids in muscle cells of farm animals are not yet fully understood.The purpose of this study was to determine the roles of carbohydrate-response element binding protein(ChREBP)and fructose in IMF deposition of chickens.For virus-mediated ChREBP overexpression in tibialis anterior(TA)muscle of chickens,seven 5-d-old male yellow-feather chickens were used.At 10 d after virus injection,the chickens were slaughtered to obtain TA muscles for analysis.For fructose administration trial,sixty 9-wk-old male yellow-feather chickens were randomly divided into 2 groups,with 6 replicates per group and 5 chickens per replicate.The chickens were fed either a basal diet or a basal diet supplemented with 10%fructose(purity≥99%).At 4 wk later,the chickens were slaughtered,and breast and thigh muscles were collected for analysis.The results showed that the skeletal ChREBP mRNA levels were positively associated with IMF content in multiple species,including the chickens,pigs,and mice(P<0.05).ChREBP overexpression increased lipid accumulation in both muscle cells in vitro and the TA muscles of mice and chickens in vivo(P<0.05),by activation of the de novo lipogenesis(DNL)pathway.Moreover,activation of ChREBP by dietary fructose administration also resulted in increased IMF content in mice and notably chickens(P<0.05).Furthermore,the lipidomics analysis revealed that ChREBP activation altered the lipid composition of chicken IMF and tented to improve the flavor profile of the meat.In conclusion,this study found that ChREBP plays a pivotal role in mediating the deposition of fat in chicken muscles in response to fructose-rich diets,which provides a novel strategy for improving meat quality in the livestock industry.展开更多
To investigate the role of glucose in regulating milk fatty acid synthesis,6 lactating Guanzhong dairy goats were infused with 0,60,or 100 g/d glucose via the external pubic artery in a 33 repeated Latin square experi...To investigate the role of glucose in regulating milk fatty acid synthesis,6 lactating Guanzhong dairy goats were infused with 0,60,or 100 g/d glucose via the external pubic artery in a 33 repeated Latin square experiment.A concomitant in vitro experiment was conducted to investigate possible mechanisms whereby glucose regulates milk fatty acid synthesis.RNA sequencing was used for cellular transcriptome analysis.Drugs,MK-2206,rapamycin,and dorsomorphin were used to block cellular mammalian AMP-activated protein kinase(AMPK),AKT serine/threonine kinase 1,and mechanistic target of rapamycin kinase signaling pathways,respectively.Carbohydrate response element binding protein(ChREBP)was knockdown and overexpressed to investigate its role in regulating milk fatty acid synthesis in mammary epithelial cells.Glucose infusion linearly elevated the concentration of C8:0(P=0.039)and C10:0(P=0.041)in milk fat while it linearly decreased(P=0.049)that of C16:0.This result was in agreement with the upregulation of genes related to de novo synthesis of fatty acids and lipid droplet formation,including adipose differentiation-related protein,butyrophilin subfamily 1 member A1,fatty acid synthase(FASN)and ChREBP.Their expression increased(P<0.05)linearly in the lactating goat mammary gland.In vitro,glucose linearly stimulated the expression of genes related to de novo synthesis of fatty acids and cellular triacylglycerol in cultured mammary epithelial cells.RNA sequencing and inhibition studies revealed that glucose induced transcriptomic changes increasing lipogenic pathways,with AMPK responding to glucose by controlling ChREBP and FASN.Knockdown and overexpression of ChREBP highlighted its essential role in lipogenesis.The knockdown and overexpression of ChREBP protein also revealed an essential role in regulating the de novo synthesis of fatty acids.Collectively,our data highlight that glucose supplementation promotes de novo fatty acid synthesis via the AMPK-ChREBP axis,hence increasing milk fat yield in the goat mammary glan展开更多
Carnivorous fish have poor tolerance to carbohydrate in feed and low utilization rate of carbohydrate.Therefore,the balance of carbohydrate and lipids in the nutrient metabolism of carnivorous fish,the ef fective conv...Carnivorous fish have poor tolerance to carbohydrate in feed and low utilization rate of carbohydrate.Therefore,the balance of carbohydrate and lipids in the nutrient metabolism of carnivorous fish,the ef fective conversion and utilization of carbohydrate and lipids,and the feedback regulation of feeding are the key links for the e fficient utilization of carnivorous fish feed.Carbohydrate response element binding protein(ChREBP)is a new transcription factor found in recent years in the glucose signaling pathway,and can also participate in feeding regulation.We performed in-vivo and in-vitro experiments to reveal the role of ChREBP in the glucose metabolism and feeding in mandarin fish.The mRNA expression of ChREBP and appetite regulatory factors were measured after intraperitoneal injection of glucose in mandarin fish Siniperca chuatsi and cotransfection with glucose and glucose+siRNA in the hypothalamic cells in mandarin fish.The results reveal that at hour 2 and 4 post intraperitoneal injection with 1 mg/g BW glucose,the blood glucose level of the mandarin fish increased significantly,but food intake decreased significantly,and it also displayed a significantly increased ChREBP mRNA expression levels in liver.At hour 4 post injection,hypothalamic ChREBP mRNA level was significantly increased,whereas the mRNA expression levels of appetite genes neuropeptide Y(npy)and agouti-related peptide(AgRP)were decreased significantly.When the glucose concentration was 40 mmol/L,the expression level of ChREBP mRNA in mandarin fish hypothalamic cells was significantly up-regulated,but the expression level of appetite gene npy mRNA was down-regulated.When siRNA and glucose were co-transfected into mandarin fish brain cells,the expression level of chrebp mRNA was significantly decreased,and the appetite gene npy mRNA was significantly increased.The results indicated that glucose regulated food intake through the modulation of appetite gene npy by ChREBP.展开更多
目的研究2型糖尿病(T2DM)患者血清碳水化合物反应元件结合蛋白(ChREBP)水平变化及与糖尿病肾病(DN)的关系。方法选取2016年2月~2018年12月辽宁省阜新市第二人民医院(妇产医院)(以下简称“我院”)收治的T2DM患者193例,根据尿白蛋白肌酐比...目的研究2型糖尿病(T2DM)患者血清碳水化合物反应元件结合蛋白(ChREBP)水平变化及与糖尿病肾病(DN)的关系。方法选取2016年2月~2018年12月辽宁省阜新市第二人民医院(妇产医院)(以下简称“我院”)收治的T2DM患者193例,根据尿白蛋白肌酐比值(UACR)结果进行分组,UACR≤30的患者为单纯T2DM组(123例),UACR>30的患者为DN组(70例)。另取同期在我院接受体检的50名健康人作为对照组。比较三组临床资料,酶联免疫吸附试验检测血清ChREBP水平,logistic回归分析DN影响因素,受试者工作特征曲线分析血清ChREBP诊断DN的能效。结果DN组糖尿病病程长于T2DM组(P<0.05);T2DM组、DN组的空腹血糖(FBG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均高于对照组,而高密度脂蛋白胆固醇(HDL-C)低于对照组(均P<0.05);DN组24 h尿白蛋白排泄率(24 h UAER)、ChREBP水平高于对照组、T2DM组,肾小球滤过率(eGFR)低于对照组、T2DM组(均P<0.05);T2DM组24 h UAER、ChREBP水平高于对照组,eGFR低于对照组(均P<0.05)。糖尿病病程、24 h UAER以及ChREBP均是DN的独立危险因素。截断值为154.36 ng/mL时,灵敏度为0.872,特异度为0.834。结论血清ChREBP水平在DN患者中异常高表达,临床可检测血清ChREBP水平用于早期DN的诊断。展开更多
转录因子碳水化合物反应元件结合蛋白(carbohydrate response element binding protein,ChREBP)可结合糖酵解和脂肪合成相关基因,调控糖脂代谢。糖脂代谢不仅是代谢疾病,如糖尿病和肥胖症等的研究热点,也是提高肉质品质、培育优良畜禽...转录因子碳水化合物反应元件结合蛋白(carbohydrate response element binding protein,ChREBP)可结合糖酵解和脂肪合成相关基因,调控糖脂代谢。糖脂代谢不仅是代谢疾病,如糖尿病和肥胖症等的研究热点,也是提高肉质品质、培育优良畜禽品种的关注点。主要综述了ChREBP的结构、组织分布、生物学功能及影响其表达的因素,以期能够为更好地调控糖脂代谢提供理论基础。展开更多
基金funded by grants from the Specific Research Project of Guangxi for Research Bases and Talents (AD22035061)the National Natural Science Foundation of China (82100913 and 82360166)the Project of Bama County for Talents in Science and Technology (20220016).
文摘The intracellular lipids in muscle cells of farm animals play a crucial role in determining the overall intramuscular fat(IMF)content,which has a positive impact on meat quality.However,the mechanisms underlying the deposition of lipids in muscle cells of farm animals are not yet fully understood.The purpose of this study was to determine the roles of carbohydrate-response element binding protein(ChREBP)and fructose in IMF deposition of chickens.For virus-mediated ChREBP overexpression in tibialis anterior(TA)muscle of chickens,seven 5-d-old male yellow-feather chickens were used.At 10 d after virus injection,the chickens were slaughtered to obtain TA muscles for analysis.For fructose administration trial,sixty 9-wk-old male yellow-feather chickens were randomly divided into 2 groups,with 6 replicates per group and 5 chickens per replicate.The chickens were fed either a basal diet or a basal diet supplemented with 10%fructose(purity≥99%).At 4 wk later,the chickens were slaughtered,and breast and thigh muscles were collected for analysis.The results showed that the skeletal ChREBP mRNA levels were positively associated with IMF content in multiple species,including the chickens,pigs,and mice(P<0.05).ChREBP overexpression increased lipid accumulation in both muscle cells in vitro and the TA muscles of mice and chickens in vivo(P<0.05),by activation of the de novo lipogenesis(DNL)pathway.Moreover,activation of ChREBP by dietary fructose administration also resulted in increased IMF content in mice and notably chickens(P<0.05).Furthermore,the lipidomics analysis revealed that ChREBP activation altered the lipid composition of chicken IMF and tented to improve the flavor profile of the meat.In conclusion,this study found that ChREBP plays a pivotal role in mediating the deposition of fat in chicken muscles in response to fructose-rich diets,which provides a novel strategy for improving meat quality in the livestock industry.
基金the National Natural Science Foundation of China(31702090)the Fundamental Research Funds for the Central Universities(2020QNA6029 and 2021FZZX003-02-06).
文摘To investigate the role of glucose in regulating milk fatty acid synthesis,6 lactating Guanzhong dairy goats were infused with 0,60,or 100 g/d glucose via the external pubic artery in a 33 repeated Latin square experiment.A concomitant in vitro experiment was conducted to investigate possible mechanisms whereby glucose regulates milk fatty acid synthesis.RNA sequencing was used for cellular transcriptome analysis.Drugs,MK-2206,rapamycin,and dorsomorphin were used to block cellular mammalian AMP-activated protein kinase(AMPK),AKT serine/threonine kinase 1,and mechanistic target of rapamycin kinase signaling pathways,respectively.Carbohydrate response element binding protein(ChREBP)was knockdown and overexpressed to investigate its role in regulating milk fatty acid synthesis in mammary epithelial cells.Glucose infusion linearly elevated the concentration of C8:0(P=0.039)and C10:0(P=0.041)in milk fat while it linearly decreased(P=0.049)that of C16:0.This result was in agreement with the upregulation of genes related to de novo synthesis of fatty acids and lipid droplet formation,including adipose differentiation-related protein,butyrophilin subfamily 1 member A1,fatty acid synthase(FASN)and ChREBP.Their expression increased(P<0.05)linearly in the lactating goat mammary gland.In vitro,glucose linearly stimulated the expression of genes related to de novo synthesis of fatty acids and cellular triacylglycerol in cultured mammary epithelial cells.RNA sequencing and inhibition studies revealed that glucose induced transcriptomic changes increasing lipogenic pathways,with AMPK responding to glucose by controlling ChREBP and FASN.Knockdown and overexpression of ChREBP highlighted its essential role in lipogenesis.The knockdown and overexpression of ChREBP protein also revealed an essential role in regulating the de novo synthesis of fatty acids.Collectively,our data highlight that glucose supplementation promotes de novo fatty acid synthesis via the AMPK-ChREBP axis,hence increasing milk fat yield in the goat mammary glan
基金Supported by the China Agriculture Research System (No.CARS-46)the National Key R&D Program of China (No.2018YFD0900400)。
文摘Carnivorous fish have poor tolerance to carbohydrate in feed and low utilization rate of carbohydrate.Therefore,the balance of carbohydrate and lipids in the nutrient metabolism of carnivorous fish,the ef fective conversion and utilization of carbohydrate and lipids,and the feedback regulation of feeding are the key links for the e fficient utilization of carnivorous fish feed.Carbohydrate response element binding protein(ChREBP)is a new transcription factor found in recent years in the glucose signaling pathway,and can also participate in feeding regulation.We performed in-vivo and in-vitro experiments to reveal the role of ChREBP in the glucose metabolism and feeding in mandarin fish.The mRNA expression of ChREBP and appetite regulatory factors were measured after intraperitoneal injection of glucose in mandarin fish Siniperca chuatsi and cotransfection with glucose and glucose+siRNA in the hypothalamic cells in mandarin fish.The results reveal that at hour 2 and 4 post intraperitoneal injection with 1 mg/g BW glucose,the blood glucose level of the mandarin fish increased significantly,but food intake decreased significantly,and it also displayed a significantly increased ChREBP mRNA expression levels in liver.At hour 4 post injection,hypothalamic ChREBP mRNA level was significantly increased,whereas the mRNA expression levels of appetite genes neuropeptide Y(npy)and agouti-related peptide(AgRP)were decreased significantly.When the glucose concentration was 40 mmol/L,the expression level of ChREBP mRNA in mandarin fish hypothalamic cells was significantly up-regulated,but the expression level of appetite gene npy mRNA was down-regulated.When siRNA and glucose were co-transfected into mandarin fish brain cells,the expression level of chrebp mRNA was significantly decreased,and the appetite gene npy mRNA was significantly increased.The results indicated that glucose regulated food intake through the modulation of appetite gene npy by ChREBP.
基金supported by the National Natural Science Foundation of China(No.30800399)the Construction Project of Key Laboratory of Shanxi Province(No.2014011049-12)+1 种基金the Scientific and Technological Innovation Foundation of Shanxi Medical UniversityChina(No.01201406)
文摘目的研究2型糖尿病(T2DM)患者血清碳水化合物反应元件结合蛋白(ChREBP)水平变化及与糖尿病肾病(DN)的关系。方法选取2016年2月~2018年12月辽宁省阜新市第二人民医院(妇产医院)(以下简称“我院”)收治的T2DM患者193例,根据尿白蛋白肌酐比值(UACR)结果进行分组,UACR≤30的患者为单纯T2DM组(123例),UACR>30的患者为DN组(70例)。另取同期在我院接受体检的50名健康人作为对照组。比较三组临床资料,酶联免疫吸附试验检测血清ChREBP水平,logistic回归分析DN影响因素,受试者工作特征曲线分析血清ChREBP诊断DN的能效。结果DN组糖尿病病程长于T2DM组(P<0.05);T2DM组、DN组的空腹血糖(FBG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均高于对照组,而高密度脂蛋白胆固醇(HDL-C)低于对照组(均P<0.05);DN组24 h尿白蛋白排泄率(24 h UAER)、ChREBP水平高于对照组、T2DM组,肾小球滤过率(eGFR)低于对照组、T2DM组(均P<0.05);T2DM组24 h UAER、ChREBP水平高于对照组,eGFR低于对照组(均P<0.05)。糖尿病病程、24 h UAER以及ChREBP均是DN的独立危险因素。截断值为154.36 ng/mL时,灵敏度为0.872,特异度为0.834。结论血清ChREBP水平在DN患者中异常高表达,临床可检测血清ChREBP水平用于早期DN的诊断。
文摘转录因子碳水化合物反应元件结合蛋白(carbohydrate response element binding protein,ChREBP)可结合糖酵解和脂肪合成相关基因,调控糖脂代谢。糖脂代谢不仅是代谢疾病,如糖尿病和肥胖症等的研究热点,也是提高肉质品质、培育优良畜禽品种的关注点。主要综述了ChREBP的结构、组织分布、生物学功能及影响其表达的因素,以期能够为更好地调控糖脂代谢提供理论基础。
