目的研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP1c)对肠道糖异生的调控作用。方法饥饿处理C57BL/6小鼠、SREBP1c纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)小鼠,通过qPCR、Western blot检...目的研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP1c)对肠道糖异生的调控作用。方法饥饿处理C57BL/6小鼠、SREBP1c纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)小鼠,通过qPCR、Western blot检测糖异生途径限速酶葡萄糖-6-磷酸酶(glucose-6-phosphatase catalytic,G6PC)和磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase 1,PCK1)在肝脏、空肠和回肠组织中的表达水平;在肠上皮细胞CaCo-2中过表达或敲低SREBP1c,检测细胞内G6PC和PCK1表达水平。结果饥饿处理后,C57BL/6小鼠空肠、回肠组织中G6PC、PCK1和SREBP1c表达水平均显著增加(P<0.05)。SREBP1c基因敲除后,小鼠空肠、回肠组织中由饥饿诱导的糖异生限速酶G6PC和PCK1的表达明显下调(P<0.05)。在肠上皮细胞CaCo-2中过表达SREBP1c,可显著上调糖异生途径关键酶G6PC和PCK1的表达,促进细胞内葡萄糖的产生(P<0.05);反之,敲低SREBP1c的表达,可明显下调G6PC和PCK1,抑制细胞内葡萄糖的产生(P<0.05)。结论饥饿状态下,SREBP1c可调控肠上皮细胞中糖异生限速酶G6PC和PCK1的表达,进而影响葡萄糖的生成,表明SREBP1c可能参与肠道糖异生的调控,机制有待进一步探索。展开更多
目的研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP1c)缺失对小鼠肠道菌群结构的影响。方法以SREBP1c基因敲除鼠为研究对象,收集纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)的小鼠粪便,采用16S ...目的研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP1c)缺失对小鼠肠道菌群结构的影响。方法以SREBP1c基因敲除鼠为研究对象,收集纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)的小鼠粪便,采用16S rDNA测序粪便基因组DNA,采用物种分类学分析、多样性指数分析、聚类分析、主成分分析(principal component analysis,PCA)等,比较敲除型和野生型两组小鼠肠道菌群结构的组成差异。检测两组小鼠肝脏脂合成代谢以及肠道屏障的差异。结果常规饲养下,SREBP1c基因敲除对小鼠的体重及肝脏总胆固醇含量(total cholesterol,TC)没有显著影响,明显减少肝脏内甘油三酯(triglyceride,TG)含量。α多样性指数(Sobs指数)分析发现,SREBP1c-KO小鼠的肠道菌群多样性显著低于野生型小鼠(P<0.01);PCA分析显示,两组小鼠肠道菌群组成有一定程度的差异。在门水平,厚壁菌门与拟杆菌门比值在SREBP1c-KO小鼠肠道中有上升趋势,但没有统计学差异;在属水平,相较于野生型小鼠,SREBP1c-KO小鼠肠道的理研菌属(Rikenella)相对丰度显著减少(P<0.05),同时肠道抗菌肽Reg3γ和紧密连接蛋白Occludin表达显著下调。结论脂代谢关键调控基因SREBP1c缺失降低小鼠肠道菌群多样性,减少理研菌属相对丰度水平,可能与肠道屏障减弱有关。展开更多
目的:探讨玉米须总皂苷对非酒精性脂肪肝(Nonal coholic Fatty Liver Disease,NAFLD)大鼠肝脏固醇调节元件结合蛋白1c(Sterol Regulatory Element Binding Protein 1c,SREBP1c)和乙酰辅酶羧化酶α(Acetyl CoA car boxyl aseα,ACCα)表...目的:探讨玉米须总皂苷对非酒精性脂肪肝(Nonal coholic Fatty Liver Disease,NAFLD)大鼠肝脏固醇调节元件结合蛋白1c(Sterol Regulatory Element Binding Protein 1c,SREBP1c)和乙酰辅酶羧化酶α(Acetyl CoA car boxyl aseα,ACCα)表达的影响。方法:将雄性SD大鼠60只随机分为正常组,模型组和治疗组,每组20只,造模成功后,治疗组给予玉米须总皂苷4 mg/(kg·d)灌胃,正常组和模型组给生理盐水灌胃,于治疗4周和8周后分别处死大鼠各半,HE染色检测肝脏病理学,普通试剂盒检测血脂,酶联免疫吸附实验(ELI SA)试剂盒检测肝功能谷草转氨酶(AST)和谷丙转氨酶(ALT),同时采用RT-PCR以及蛋白免疫印迹法(Western Blot)检测肝脏组织SREBP1c和ACCα的表达。结果:与正常组相比,模型组大鼠肝功能指标AST和ALT,血脂指标甘油三酯(TG)和游离脂肪酸(FFA)升高(P<0. 05),与模型组相比,玉米须总皂苷治疗4周后,其AST、ALT、TG以及FFA均下降(P<0. 05);治疗8周后进一步降低(P<0. 05);与正常组相比,模型组SREBP1c和ACCα表达升高(P<0. 05),与模型组相比,玉米须总皂苷治疗4周后降低,治疗8周后进一步降低(P<0. 05)。结论:玉米须总皂苷对非酒精性脂肪肝病大鼠肝功能和血脂有改善作用,这可能与其可以降低肝脏脂肪酸α氧化关键酶SREBP1c和ACCα有关。展开更多
Background: The effects of whey protein intake on the transcriptional expression of genes related to lipid metabolism in mice were investigated herein. Methods: For 4 weeks, mice were fed AIN-93G composed of either ca...Background: The effects of whey protein intake on the transcriptional expression of genes related to lipid metabolism in mice were investigated herein. Methods: For 4 weeks, mice were fed AIN-93G composed of either casein or whey protein as the protein source. Then the gastrocnemius muscle, liver, and epididymal adipose tissue were excised. Expression levels of the transcription factors, PPARα, PPARγ, and SREBP1c, and those of the enzymes modulated by these factors, HSL, LPL, ACCα, and FAS, were measured by real-time PCR. The effects of whey protein were compared to those of the case in control. Results: The mRNA expression of PPARα was enhanced in the gastrocnemius muscle, while that of PPARγ was increased in the liver and epididymal adipose tissue. The expression of HSL and LPL was increased in the epididymal adipose tissue and gastrocnemius muscle, respectively. The mRNA expression of SREBP1c was suppressed in all of the three tissues. The expression of ACCα was suppressed in the gastrocnemius muscle and liver, while that of FAS was suppressed in all of the three tissues. Conclusions: These results indicate that whey protein intakes transcriptionally modulate PPARs and SREBP1c directing lipid metabolism toward the enhancement of triglyceride breakdown and suppression of fatty acid synthesis.展开更多
Background: De novo lipogenesis (DNL) is a critical event for the development of tumors, in the present work,we revealed the role of propofol in colorectal cancer (CRC) cell proliferation. Methods: Western blotting (W...Background: De novo lipogenesis (DNL) is a critical event for the development of tumors, in the present work,we revealed the role of propofol in colorectal cancer (CRC) cell proliferation. Methods: Western blotting (WB), Real-timePCR, and luciferase combined with chromatin immunoprecipitation (ChIP) were used to identify the mechanismunderlying propofol-modulated cell proliferation in CRC cells. Results: Herein, we showed that propofol suppressedcell proliferation, which was attributed to the inhibition of DNL characterized by reduced fatty acid synthase (FASN),acetyl-coA carboxylase alpha (ACCA), and stearoyl-coA desaturase-1 (SCD1) expression. Mechanically, propofolstimulation decreased sterol regulatory element-binding proteins-1c (SREBP-1c) mature and nuclear translocation,which further decreased SCD1 transactivation confirmed by luciferase and ChIP analysis, while no significantdifference in total SREBP1c was observed. What’s more, supplementation of Monounsaturated fatty acid (MuFA)could reverse the inhibitory effect of propofol on cell proliferation. Conclusion: Taken together, these resultssuggested propofol modulated cell proliferation is dependent on SREBP1c-mediated DNL.展开更多
Objective To investigate the serum and follicular fluid levels of sterol regulatory element-binding protein 1 c(SREBP-lc),leucine-rich α-2-glycoprotein 1 (LRG1)and the correlation with insulin resistance (IR) in nono...Objective To investigate the serum and follicular fluid levels of sterol regulatory element-binding protein 1 c(SREBP-lc),leucine-rich α-2-glycoprotein 1 (LRG1)and the correlation with insulin resistance (IR) in nonovarian etiology infertility patients and polycystic ovary syndrome (PCOS) patients with or without IR.展开更多
Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this stud...Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this study:three groups were given streptozotocin to induce diabetes,and one group was given a normal control.For treatment groups,each group received either metformin(200 mg/kg body weight)or quercetin(50 mg/kg body weight)for a month.The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins(TGF-βand p-Smad3)was evaluated by Western blot.Furthermore,MCP and IL-1βwere determined by ELISA.Results:Quercetin significantly reduced insulin and glucose levels.Besides,it reduced the serum levels of ALT,AST,and ALP,improved lipid profile,lowered the MDA level,increased SOD activity,decreased the rise in MCP-1 and IL-1β,inhibited the TGF-β/Smad3 signaling pathway,decreasedα-SMA and SREBP1c expression,and increased AMPK(P<0.05).Conclusions:Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.展开更多
文摘目的研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP1c)对肠道糖异生的调控作用。方法饥饿处理C57BL/6小鼠、SREBP1c纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)小鼠,通过qPCR、Western blot检测糖异生途径限速酶葡萄糖-6-磷酸酶(glucose-6-phosphatase catalytic,G6PC)和磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase 1,PCK1)在肝脏、空肠和回肠组织中的表达水平;在肠上皮细胞CaCo-2中过表达或敲低SREBP1c,检测细胞内G6PC和PCK1表达水平。结果饥饿处理后,C57BL/6小鼠空肠、回肠组织中G6PC、PCK1和SREBP1c表达水平均显著增加(P<0.05)。SREBP1c基因敲除后,小鼠空肠、回肠组织中由饥饿诱导的糖异生限速酶G6PC和PCK1的表达明显下调(P<0.05)。在肠上皮细胞CaCo-2中过表达SREBP1c,可显著上调糖异生途径关键酶G6PC和PCK1的表达,促进细胞内葡萄糖的产生(P<0.05);反之,敲低SREBP1c的表达,可明显下调G6PC和PCK1,抑制细胞内葡萄糖的产生(P<0.05)。结论饥饿状态下,SREBP1c可调控肠上皮细胞中糖异生限速酶G6PC和PCK1的表达,进而影响葡萄糖的生成,表明SREBP1c可能参与肠道糖异生的调控,机制有待进一步探索。
文摘目的研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP1c)缺失对小鼠肠道菌群结构的影响。方法以SREBP1c基因敲除鼠为研究对象,收集纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)的小鼠粪便,采用16S rDNA测序粪便基因组DNA,采用物种分类学分析、多样性指数分析、聚类分析、主成分分析(principal component analysis,PCA)等,比较敲除型和野生型两组小鼠肠道菌群结构的组成差异。检测两组小鼠肝脏脂合成代谢以及肠道屏障的差异。结果常规饲养下,SREBP1c基因敲除对小鼠的体重及肝脏总胆固醇含量(total cholesterol,TC)没有显著影响,明显减少肝脏内甘油三酯(triglyceride,TG)含量。α多样性指数(Sobs指数)分析发现,SREBP1c-KO小鼠的肠道菌群多样性显著低于野生型小鼠(P<0.01);PCA分析显示,两组小鼠肠道菌群组成有一定程度的差异。在门水平,厚壁菌门与拟杆菌门比值在SREBP1c-KO小鼠肠道中有上升趋势,但没有统计学差异;在属水平,相较于野生型小鼠,SREBP1c-KO小鼠肠道的理研菌属(Rikenella)相对丰度显著减少(P<0.05),同时肠道抗菌肽Reg3γ和紧密连接蛋白Occludin表达显著下调。结论脂代谢关键调控基因SREBP1c缺失降低小鼠肠道菌群多样性,减少理研菌属相对丰度水平,可能与肠道屏障减弱有关。
文摘Background: The effects of whey protein intake on the transcriptional expression of genes related to lipid metabolism in mice were investigated herein. Methods: For 4 weeks, mice were fed AIN-93G composed of either casein or whey protein as the protein source. Then the gastrocnemius muscle, liver, and epididymal adipose tissue were excised. Expression levels of the transcription factors, PPARα, PPARγ, and SREBP1c, and those of the enzymes modulated by these factors, HSL, LPL, ACCα, and FAS, were measured by real-time PCR. The effects of whey protein were compared to those of the case in control. Results: The mRNA expression of PPARα was enhanced in the gastrocnemius muscle, while that of PPARγ was increased in the liver and epididymal adipose tissue. The expression of HSL and LPL was increased in the epididymal adipose tissue and gastrocnemius muscle, respectively. The mRNA expression of SREBP1c was suppressed in all of the three tissues. The expression of ACCα was suppressed in the gastrocnemius muscle and liver, while that of FAS was suppressed in all of the three tissues. Conclusions: These results indicate that whey protein intakes transcriptionally modulate PPARs and SREBP1c directing lipid metabolism toward the enhancement of triglyceride breakdown and suppression of fatty acid synthesis.
基金supported by Zhuhai Science and Technology Plan Project in the Field of Social Development(2320004000157)National Natural Science Foundation of China(82072215,82272219)+1 种基金Shenzhen Science and Technology Program(JCYJ20210324134602006)Natural Science Foundation of Guangdong Province(2214050001873).
文摘Background: De novo lipogenesis (DNL) is a critical event for the development of tumors, in the present work,we revealed the role of propofol in colorectal cancer (CRC) cell proliferation. Methods: Western blotting (WB), Real-timePCR, and luciferase combined with chromatin immunoprecipitation (ChIP) were used to identify the mechanismunderlying propofol-modulated cell proliferation in CRC cells. Results: Herein, we showed that propofol suppressedcell proliferation, which was attributed to the inhibition of DNL characterized by reduced fatty acid synthase (FASN),acetyl-coA carboxylase alpha (ACCA), and stearoyl-coA desaturase-1 (SCD1) expression. Mechanically, propofolstimulation decreased sterol regulatory element-binding proteins-1c (SREBP-1c) mature and nuclear translocation,which further decreased SCD1 transactivation confirmed by luciferase and ChIP analysis, while no significantdifference in total SREBP1c was observed. What’s more, supplementation of Monounsaturated fatty acid (MuFA)could reverse the inhibitory effect of propofol on cell proliferation. Conclusion: Taken together, these resultssuggested propofol modulated cell proliferation is dependent on SREBP1c-mediated DNL.
文摘Objective To investigate the serum and follicular fluid levels of sterol regulatory element-binding protein 1 c(SREBP-lc),leucine-rich α-2-glycoprotein 1 (LRG1)and the correlation with insulin resistance (IR) in nonovarian etiology infertility patients and polycystic ovary syndrome (PCOS) patients with or without IR.
文摘Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this study:three groups were given streptozotocin to induce diabetes,and one group was given a normal control.For treatment groups,each group received either metformin(200 mg/kg body weight)or quercetin(50 mg/kg body weight)for a month.The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins(TGF-βand p-Smad3)was evaluated by Western blot.Furthermore,MCP and IL-1βwere determined by ELISA.Results:Quercetin significantly reduced insulin and glucose levels.Besides,it reduced the serum levels of ALT,AST,and ALP,improved lipid profile,lowered the MDA level,increased SOD activity,decreased the rise in MCP-1 and IL-1β,inhibited the TGF-β/Smad3 signaling pathway,decreasedα-SMA and SREBP1c expression,and increased AMPK(P<0.05).Conclusions:Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.
