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
鸭ChREBP(carbohydrate response element binding protein,碳水化合物反应元件结合蛋白),是鸭糖酵解脂肪酸从头合成的重要调节因子之一,对调节机体糖脂代谢平衡有重要作用;本研究以PCR-SSCP结合直接测序对三穗鸭、兴义鸭、樱桃谷鸭3个...鸭ChREBP(carbohydrate response element binding protein,碳水化合物反应元件结合蛋白),是鸭糖酵解脂肪酸从头合成的重要调节因子之一,对调节机体糖脂代谢平衡有重要作用;本研究以PCR-SSCP结合直接测序对三穗鸭、兴义鸭、樱桃谷鸭3个鸭品种ChREBP基因外显子1、2、3、6、9、10、11、12、13进行多态性检测,分析SNPs位点与血清生化指标的关联性及对各指标的加、显性效应;结果显示,仅在樱桃谷鸭的外显子9中检测到了g.246911 G>A突变,表明鸭ChREBP基因具有良好的保守性,产生了AA、AB、BB三种基因型,A和B两个等位因,B和BB分别为该位点的优势等位基因和优势基因型,其频率为0.575和0.450,多态信息含量(PIC)为0.369,属于中度多态,卡方(χ2)检验发现,该g.246911G>A突变位点的基因型分布在樱桃谷鸭群体中严重偏离了Hardy-Weinberg平衡,可能是因为长期人工选择的原因,关联性分析结果表明,AA基因型个体的血清生化指标除低密度脂蛋白没有达到显著水平外,其他指标均显著地高于BB基因型个体(p<0.05),加、显性效应显示,该位点对总蛋白、白蛋白、球蛋白、高密度脂蛋白、低密度脂蛋白、总胆固醇具有显著的加性效应(p<0.05),对总蛋白和白蛋白有显著的负显性效应(p<0.05);推测g.246911G>A为有利突变,AA和A分别为有利基因型和等位基因,可作为今后选育优秀生长性状樱桃谷鸭的遗传标记位点。展开更多
为更好地了解及利用贵州地方鸭品种优良遗传资源,本研究随机抽取50只樱桃谷鸭(公母各半),屠宰,测其肉质及血清生化指标,荧光定量PCR检测樱桃谷鸭ChREBP m RNA的组织表达谱并分析其相关性,结果显示:ChREBP在鸭各组织中均表达,在腹脂中表...为更好地了解及利用贵州地方鸭品种优良遗传资源,本研究随机抽取50只樱桃谷鸭(公母各半),屠宰,测其肉质及血清生化指标,荧光定量PCR检测樱桃谷鸭ChREBP m RNA的组织表达谱并分析其相关性,结果显示:ChREBP在鸭各组织中均表达,在腹脂中表达量最高,除在大脑、小脑、肝、脾、腺胃和肌胃中表达量较低,属低度表达,在其它10组织中表达量相对较高,均属中高度表达。相关性结果表明,ChREBP mRNA表达丰度与白蛋白、甘油三酯、总胆固醇和高密度脂蛋白呈显著或极显著正相关(p<0.05或0.01),与低密度脂蛋白呈极显著负相关(p<0.01),与肉质指标相关但不显著(p>0.05),推测ChREBP基因在鸭调控脂质代谢方面发挥着重要作用。展开更多
Insulin can stimulate hepatic expression of carbohydrate-responsive element-binding protein （ChREBP）. As recent studies revealed potential metabolic beneficial effects of ChREBP, we asked whether its expression can ...Insulin can stimulate hepatic expression of carbohydrate-responsive element-binding protein （ChREBP）. As recent studies revealed potential metabolic beneficial effects of ChREBP, we asked whether its expression can also be regulated by the dietary polyphenoi curcumin. We also aimed to determine mechanisms underlying ChREBP stimulation by insulin and curcumin. The effect of insulin on ChREBP expression was assessed in mouse hepatocytes, while the effect of curcumin was assessed in mouse hepatocytes and with curcumin garage in mice. Chemical inhibitors for insulin signaling molecules were utilized to identify involved signaling molecules, and the involvement of p21-activated protein kinase 1 （Pakl） was determined with its chemical inhibitor and Pokl-/- hepatocytes. We found that both insulin and curcumin-stimulated ChREBP expression in Akt-independent but MEK/ERK-dependent manner, involving the inactivation of the transcriptional repressor Oct-1. Aged Pokl-/- mice showed reduced body fat volume. Pakl inhibition or its genetic deletion attenuated the stimulatory effect of insulin or curcumin on ChREBP expression. Our study hence suggests the existence of a novel signaling cascade Pakl/MEK/ERK/Oct-1 for both insulin and curcumin in exerting their glucose-lowering effect via promoting hepatic ChREBP production, supports the recognition of beneficial functions of ChREBP, and brings us a new overview on dietary polyphenols.展开更多
Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease worldwide.This study aimed to decipher the compl...Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease worldwide.This study aimed to decipher the complex role of FTO in hepatic lipid metabolism.We found that a decrease in N^(6)-methyladenosine(m^(6)A)RNA methylation in the liver of mice fed with a high-fat diet(HFD)was accompanied by an increase in FTO expression.Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes.Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1(SREBF1)and carbohydrate responsive element binding protein(ChREBP),two master lipogenic transcription factors,by demethylating m^(6)A sites.Knockdown ofeither SREBF1 or ChREBP attenuated the lipogenic effect of FTO,suggesting that they are bona fide effectors for FTO in regulating lipogenesis.Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta,while knockdown of FTO abrogated the lipogenic effect of insulin.Inhibition ofFTo by entacapone decreased the expression of SREBF1,ChREBP,and downstream lipogenic genes,ameliorating liver steatosis in HFD-fed mice.Thus,our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategyfor treating NAFLD.展开更多
高发的糖尿病、肥胖症、脂肪肝等代谢性疾病和肿瘤对生活品质和生命健康带来极大威胁,寻找更加有效的药物靶标至关重要。碳水化合物反应元件结合蛋白(carbohydrate responsive element binding protein,ChREBP)是调控糖脂代谢的转录因子...高发的糖尿病、肥胖症、脂肪肝等代谢性疾病和肿瘤对生活品质和生命健康带来极大威胁,寻找更加有效的药物靶标至关重要。碳水化合物反应元件结合蛋白(carbohydrate responsive element binding protein,ChREBP)是调控糖脂代谢的转录因子,显著影响肝脏糖酵解、脂质生成和胰岛素敏感性,在胰岛中促进β细胞适应性增殖,提示ChREBP对糖尿病等代谢性疾病的发展起重要作用。近年发现,ChREBP在肝癌、结直肠癌等肿瘤的发生发展中举足轻重。现就ChREBP的结构及特点、在正常组织和肿瘤中的作用及机制进行综述。ChREBP作为细胞代谢和肿瘤发生发展的纽带,为代谢性疾病和肿瘤研究提供了新的思路,其潜在靶标具有临床应用前景。展开更多
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.
文摘为更好地了解及利用贵州地方鸭品种优良遗传资源,本研究随机抽取50只樱桃谷鸭(公母各半),屠宰,测其肉质及血清生化指标,荧光定量PCR检测樱桃谷鸭ChREBP m RNA的组织表达谱并分析其相关性,结果显示:ChREBP在鸭各组织中均表达,在腹脂中表达量最高,除在大脑、小脑、肝、脾、腺胃和肌胃中表达量较低,属低度表达,在其它10组织中表达量相对较高,均属中高度表达。相关性结果表明,ChREBP mRNA表达丰度与白蛋白、甘油三酯、总胆固醇和高密度脂蛋白呈显著或极显著正相关(p<0.05或0.01),与低密度脂蛋白呈极显著负相关(p<0.01),与肉质指标相关但不显著(p>0.05),推测ChREBP基因在鸭调控脂质代谢方面发挥着重要作用。
文摘Insulin can stimulate hepatic expression of carbohydrate-responsive element-binding protein （ChREBP）. As recent studies revealed potential metabolic beneficial effects of ChREBP, we asked whether its expression can also be regulated by the dietary polyphenoi curcumin. We also aimed to determine mechanisms underlying ChREBP stimulation by insulin and curcumin. The effect of insulin on ChREBP expression was assessed in mouse hepatocytes, while the effect of curcumin was assessed in mouse hepatocytes and with curcumin garage in mice. Chemical inhibitors for insulin signaling molecules were utilized to identify involved signaling molecules, and the involvement of p21-activated protein kinase 1 （Pakl） was determined with its chemical inhibitor and Pokl-/- hepatocytes. We found that both insulin and curcumin-stimulated ChREBP expression in Akt-independent but MEK/ERK-dependent manner, involving the inactivation of the transcriptional repressor Oct-1. Aged Pokl-/- mice showed reduced body fat volume. Pakl inhibition or its genetic deletion attenuated the stimulatory effect of insulin or curcumin on ChREBP expression. Our study hence suggests the existence of a novel signaling cascade Pakl/MEK/ERK/Oct-1 for both insulin and curcumin in exerting their glucose-lowering effect via promoting hepatic ChREBP production, supports the recognition of beneficial functions of ChREBP, and brings us a new overview on dietary polyphenols.
基金This work was supported by the Chinese Ministry of Science and Technology(2021YFA1100500)the National Natural Science Foundation of China(NSFC,91957205,82070821,and 82000805)+4 种基金Youth Innovation Promotion Association,Chinese Academy of Sciences(2021261)Pujiang Talent Program from the Science and Technology Commission of Shanghai Municipality(21PJ1416100)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2020QNRC001)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University(2022-3-1)NHC Key Laboratory of Food Safety Risk Assessment(2020K02).
文摘Previous studies have indicated an association of fat mass and obesity-associated(FTO)with nonalcoholic fatty liver disease(NAFLD),the most common chronic liver disease worldwide.This study aimed to decipher the complex role of FTO in hepatic lipid metabolism.We found that a decrease in N^(6)-methyladenosine(m^(6)A)RNA methylation in the liver of mice fed with a high-fat diet(HFD)was accompanied by an increase in FTO expression.Overexpression of FTO in the liver promoted triglyceride accumulation by upregulating the expression of lipogenic genes.Mechanistical studies revealed that FTO could stabilize the mRNAs of sterol regulatory element binding transcription factor 1(SREBF1)and carbohydrate responsive element binding protein(ChREBP),two master lipogenic transcription factors,by demethylating m^(6)A sites.Knockdown ofeither SREBF1 or ChREBP attenuated the lipogenic effect of FTO,suggesting that they are bona fide effectors for FTO in regulating lipogenesis.Insulin could stimulate FTO transcription through a mechanism involving the action of intranuclear insulin receptor beta,while knockdown of FTO abrogated the lipogenic effect of insulin.Inhibition ofFTo by entacapone decreased the expression of SREBF1,ChREBP,and downstream lipogenic genes,ameliorating liver steatosis in HFD-fed mice.Thus,our study established a critical role of FTO in both the insulin-regulated hepatic lipogenesis and the pathogenesis of NAFLD and provided a potential strategyfor treating NAFLD.
文摘高发的糖尿病、肥胖症、脂肪肝等代谢性疾病和肿瘤对生活品质和生命健康带来极大威胁,寻找更加有效的药物靶标至关重要。碳水化合物反应元件结合蛋白(carbohydrate responsive element binding protein,ChREBP)是调控糖脂代谢的转录因子,显著影响肝脏糖酵解、脂质生成和胰岛素敏感性,在胰岛中促进β细胞适应性增殖,提示ChREBP对糖尿病等代谢性疾病的发展起重要作用。近年发现,ChREBP在肝癌、结直肠癌等肿瘤的发生发展中举足轻重。现就ChREBP的结构及特点、在正常组织和肿瘤中的作用及机制进行综述。ChREBP作为细胞代谢和肿瘤发生发展的纽带,为代谢性疾病和肿瘤研究提供了新的思路,其潜在靶标具有临床应用前景。
