Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides dista...Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.展开更多
In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known t...In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known that the clinical features of metabolic diseases can manifest themselves with very different characteristics and escape early detection. Also, it is well known that the prognosis of many metabolic diseases is excellent if diagnosed and treated early. In this editorial we briefly summarized two groups of inherited metabolic diseases, the defects of cholesterol biosynthesis and those of bile acids. Both groups show variable clinical manifestations but some clinical signs and symptoms are common in both the defects of cholesterol and bile acids. The differential diagnosis can be made analyzing sterol profiles in blood and/or bile acids in blood and urine by chromatographic techniques(GC-MS and LC-MS/MS). Several defects of both biosynthetic pathways are treatable so early diagnosis is crucial. Unfortunately their diagnosis is made too late, due either to the clinical heterogeneity of the syndromes(severe, mild and very mild) that to the scarcity of scientific dissemination of these rare diseases. Therefore, the delay in diagnosis leads the patient to the medical observation when the disease has produced irreversible damages to the body. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, as well, we suggest appropriate request of the laboratory tests that along with common clinical features can help to diagnose these defects.展开更多
AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William...AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William’s E medium.The medium wascollected and renewed every 24 h.Bile acids andtheir precursors in media were finally analysed bygas chromatography-mass spectrometry.RESULTS Cholic acid(CA)andchenodeoxycholic acid(CDCA)conjugated withglycine or taurine accounted for 70% and 25% oftotal steroids.A third of CDCA was alsoconjugated with sulphuric acid.Dexamethasoneand thyroid hormone alone or in combination didnot significantly effect bile acid formation.Theaddition of cyclosporin A(10 μmol/L)inhibited thesynthesis of CA and CDCA by about 13% and30%,respectively.CONCLUSION Isolated human hepatocytes inprimary culture behave as in the intact liver byconverting cholesterol to conjugated CA andCDCA.This is in contrast to cultured HepG2 cells,which release large amounts of bile acidprecursors and unconjugated bile acids into themedium.展开更多
目的通过观察健脾祛痰方对脾虚痰浊型血脂异常患者的血脂水平、中医证候积分的影响,分析正常与高脂人群、中药治疗前后患者肠道菌群的结构变化,以明确健脾祛痰方降脂的临床疗效,探索健脾祛痰法降脂的作用机制。方法在辽宁中医药大学附...目的通过观察健脾祛痰方对脾虚痰浊型血脂异常患者的血脂水平、中医证候积分的影响,分析正常与高脂人群、中药治疗前后患者肠道菌群的结构变化,以明确健脾祛痰方降脂的临床疗效,探索健脾祛痰法降脂的作用机制。方法在辽宁中医药大学附属医院纳入正常及脾虚痰浊血脂异常受试者共计180例,按照就诊顺序随机分为正常组、模型组、健脾祛痰方组,每组60例。所有组别均予健康宣教,健脾祛痰方组予健脾祛痰方颗粒剂冲服,治疗疗程为2个月。采用全自动分析仪检测所有受试者血清胆固醇(Total Cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low Density Lipoprotein,LDL-C)、高密度脂蛋白胆固醇(High Density Lipoprotein,HDL-C)水平,用中医证候积分量表评定患者中医证候疗效,酶联免疫吸附测定法测定受试者血清人成纤维细胞生长因子19(FGF19)的表达水平,16SrRNA高通量测序技术检测受试者粪便标本肠道菌群的结构变化。结果脾虚痰浊型血脂异常患者经健脾祛痰方治疗后血脂水平,中医证候积分较治疗前明显改善,血清中FGF19含量明显降低;健脾祛痰方组血脂疗效、中医证候积分总有效率显著优于模型组。高脂人群菌群多样性和物种丰度与正常人群相比明显减弱。有益菌减少,肠杆菌过生长,肠道菌群结构被破坏。健脾祛痰方组患者用药后样本间差异明显,各分类水平物种组成比例发生变化,编码胆盐水解酶(Bile Salt Hydrolase,BSH)相关微生物丰度降低。用药后肠道中的有害菌肠杆菌目(Enterobacteriales)减少,肠道菌群平衡有所恢复。结论健脾祛痰法能够显著降低血脂异常患者TC、TG、LDL-C水平,改善中医证候,其机制可能通过调节肠道菌群和胆汁酸代谢抑制FXR信号传导通路以降脂。展开更多
背景:运动已成为当下促进人体健康不可或缺的重要方式之一。近年肠道组织中的菌群作为预防和改善人体疾病的重要靶点,其对人体健康的重要性已逐渐得到人们的认识。当前研究已证明,运动可以介入肠道菌群对其组成、结构、功能及多样性进...背景:运动已成为当下促进人体健康不可或缺的重要方式之一。近年肠道组织中的菌群作为预防和改善人体疾病的重要靶点,其对人体健康的重要性已逐渐得到人们的认识。当前研究已证明,运动可以介入肠道菌群对其组成、结构、功能及多样性进行有效调控,从而影响机体组织健康状况。目的:文章首先对运动、肠道菌群以及机体健康3者的相关性进行系统分析,旨在进一步探究运动介入肠道菌群对机体组织健康产生影响的可能性机制;其次不同运动强度下菌群变化对机体健康影响状况进行分析,以期对相关疾病的改善和后续研究提供思路和途径。方法:检索Web of Science、Elsevier、Springer、PubMed、ProQuest、中国知网、万方数据、维普中文期刊服务平台及中国台湾学术文献数据库,检索与运动训练、肠道菌群、能量代谢、抗炎反应和氧化应激等相关的中英文文献,文献发表时间截止至2022年2月,根据研究目的确立相应的入组标准,最终筛选出97篇文献进行论述。结果与结论:①运动可以通过调节肠道菌群促进短链脂肪酸分泌促进抗炎因子白细胞介素10的增加,降低脂多糖诱导产生的相关炎症因子,从而提高机体组织抗炎能力,促进宿主健康。②运动介入肠道菌群不仅可以促进短链脂肪酸的产生也可以提高胆汁酸分泌来激活人体器官中的核激素法尼醇X受体和G蛋白偶联受体,从而调节宿主机体脂质、葡萄糖和能量代谢,促进机体各组织能量代谢吸收与稳定。③运动介入肠道菌群改变乳杆菌与双歧杆菌丰度调控抗氧化酶,如超氧化物歧化酶、过氧化氢酶及非酶系统谷胱甘肽的活性,从而调控或消除氧化应激,预防病原体入侵,改善肌肉组织损伤。④另外,有研究还发现不同强度运动对肠道菌群的影响有明显差异,从而对机体组织健康也产生不同影响,低-中强度运动介入肠道菌群可以改善肠道有益菌丰度,促进肠道稳态,对机体健康产生有益影响,而高强度运动介入肠道菌群对人体健康的影响存在较大争议。⑤目前,运动介入肠道菌群促进机体健康的相关机制尚不明朗,亟待深入研究,且对不同运动强度、运动时间、运动模式、运动对象等相关特定因素影响下肠道菌群对机体健康作用的具体研究较少,值得学者们进一步关注。展开更多
Cholesterol 7 alpha-hydroxylase(CYP7A1,EC1.14)is the first and rate-limiting enzyme in the classic bile acid synthesis pathway.Much progress has been made in understanding the transcriptional regulation of CYP7A1 gene...Cholesterol 7 alpha-hydroxylase(CYP7A1,EC1.14)is the first and rate-limiting enzyme in the classic bile acid synthesis pathway.Much progress has been made in understanding the transcriptional regulation of CYP7A1 gene expression and the underlying molecular mechanisms of bile acid feedback regulation of CYP7A1 and bile acid synthesis in the last three decades.Discovery of bile acid-activated receptors and their roles in the regulation of lipid,glucose and energy metabolism have been translated to the development of bile acid-based drug therapies for the treatment of liver-related metabolic diseases such as alcoholic and non-alcoholic fatty liver diseases,liver cirrhosis,diabetes,obesity and hepatocellular carcinoma.This review will provide an update on the advances in our understanding of the molecular biology and mechanistic insights of the regulation of CYP7A1 in bile acid synthesis in the last 40 years.展开更多
基金supported by the National Natural Science Foundation of China(32272331)。
文摘Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.
文摘In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known that the clinical features of metabolic diseases can manifest themselves with very different characteristics and escape early detection. Also, it is well known that the prognosis of many metabolic diseases is excellent if diagnosed and treated early. In this editorial we briefly summarized two groups of inherited metabolic diseases, the defects of cholesterol biosynthesis and those of bile acids. Both groups show variable clinical manifestations but some clinical signs and symptoms are common in both the defects of cholesterol and bile acids. The differential diagnosis can be made analyzing sterol profiles in blood and/or bile acids in blood and urine by chromatographic techniques(GC-MS and LC-MS/MS). Several defects of both biosynthetic pathways are treatable so early diagnosis is crucial. Unfortunately their diagnosis is made too late, due either to the clinical heterogeneity of the syndromes(severe, mild and very mild) that to the scarcity of scientific dissemination of these rare diseases. Therefore, the delay in diagnosis leads the patient to the medical observation when the disease has produced irreversible damages to the body. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, as well, we suggest appropriate request of the laboratory tests that along with common clinical features can help to diagnose these defects.
基金the Swedish Medical Research Council(03X-4793 and 03X-7890)
文摘AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William’s E medium.The medium wascollected and renewed every 24 h.Bile acids andtheir precursors in media were finally analysed bygas chromatography-mass spectrometry.RESULTS Cholic acid(CA)andchenodeoxycholic acid(CDCA)conjugated withglycine or taurine accounted for 70% and 25% oftotal steroids.A third of CDCA was alsoconjugated with sulphuric acid.Dexamethasoneand thyroid hormone alone or in combination didnot significantly effect bile acid formation.Theaddition of cyclosporin A(10 μmol/L)inhibited thesynthesis of CA and CDCA by about 13% and30%,respectively.CONCLUSION Isolated human hepatocytes inprimary culture behave as in the intact liver byconverting cholesterol to conjugated CA andCDCA.This is in contrast to cultured HepG2 cells,which release large amounts of bile acidprecursors and unconjugated bile acids into themedium.
文摘目的通过观察健脾祛痰方对脾虚痰浊型血脂异常患者的血脂水平、中医证候积分的影响,分析正常与高脂人群、中药治疗前后患者肠道菌群的结构变化,以明确健脾祛痰方降脂的临床疗效,探索健脾祛痰法降脂的作用机制。方法在辽宁中医药大学附属医院纳入正常及脾虚痰浊血脂异常受试者共计180例,按照就诊顺序随机分为正常组、模型组、健脾祛痰方组,每组60例。所有组别均予健康宣教,健脾祛痰方组予健脾祛痰方颗粒剂冲服,治疗疗程为2个月。采用全自动分析仪检测所有受试者血清胆固醇(Total Cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白胆固醇(Low Density Lipoprotein,LDL-C)、高密度脂蛋白胆固醇(High Density Lipoprotein,HDL-C)水平,用中医证候积分量表评定患者中医证候疗效,酶联免疫吸附测定法测定受试者血清人成纤维细胞生长因子19(FGF19)的表达水平,16SrRNA高通量测序技术检测受试者粪便标本肠道菌群的结构变化。结果脾虚痰浊型血脂异常患者经健脾祛痰方治疗后血脂水平,中医证候积分较治疗前明显改善,血清中FGF19含量明显降低;健脾祛痰方组血脂疗效、中医证候积分总有效率显著优于模型组。高脂人群菌群多样性和物种丰度与正常人群相比明显减弱。有益菌减少,肠杆菌过生长,肠道菌群结构被破坏。健脾祛痰方组患者用药后样本间差异明显,各分类水平物种组成比例发生变化,编码胆盐水解酶(Bile Salt Hydrolase,BSH)相关微生物丰度降低。用药后肠道中的有害菌肠杆菌目(Enterobacteriales)减少,肠道菌群平衡有所恢复。结论健脾祛痰法能够显著降低血脂异常患者TC、TG、LDL-C水平,改善中医证候,其机制可能通过调节肠道菌群和胆汁酸代谢抑制FXR信号传导通路以降脂。
文摘背景:运动已成为当下促进人体健康不可或缺的重要方式之一。近年肠道组织中的菌群作为预防和改善人体疾病的重要靶点,其对人体健康的重要性已逐渐得到人们的认识。当前研究已证明,运动可以介入肠道菌群对其组成、结构、功能及多样性进行有效调控,从而影响机体组织健康状况。目的:文章首先对运动、肠道菌群以及机体健康3者的相关性进行系统分析,旨在进一步探究运动介入肠道菌群对机体组织健康产生影响的可能性机制;其次不同运动强度下菌群变化对机体健康影响状况进行分析,以期对相关疾病的改善和后续研究提供思路和途径。方法:检索Web of Science、Elsevier、Springer、PubMed、ProQuest、中国知网、万方数据、维普中文期刊服务平台及中国台湾学术文献数据库,检索与运动训练、肠道菌群、能量代谢、抗炎反应和氧化应激等相关的中英文文献,文献发表时间截止至2022年2月,根据研究目的确立相应的入组标准,最终筛选出97篇文献进行论述。结果与结论:①运动可以通过调节肠道菌群促进短链脂肪酸分泌促进抗炎因子白细胞介素10的增加,降低脂多糖诱导产生的相关炎症因子,从而提高机体组织抗炎能力,促进宿主健康。②运动介入肠道菌群不仅可以促进短链脂肪酸的产生也可以提高胆汁酸分泌来激活人体器官中的核激素法尼醇X受体和G蛋白偶联受体,从而调节宿主机体脂质、葡萄糖和能量代谢,促进机体各组织能量代谢吸收与稳定。③运动介入肠道菌群改变乳杆菌与双歧杆菌丰度调控抗氧化酶,如超氧化物歧化酶、过氧化氢酶及非酶系统谷胱甘肽的活性,从而调控或消除氧化应激,预防病原体入侵,改善肌肉组织损伤。④另外,有研究还发现不同强度运动对肠道菌群的影响有明显差异,从而对机体组织健康也产生不同影响,低-中强度运动介入肠道菌群可以改善肠道有益菌丰度,促进肠道稳态,对机体健康产生有益影响,而高强度运动介入肠道菌群对人体健康的影响存在较大争议。⑤目前,运动介入肠道菌群促进机体健康的相关机制尚不明朗,亟待深入研究,且对不同运动强度、运动时间、运动模式、运动对象等相关特定因素影响下肠道菌群对机体健康作用的具体研究较少,值得学者们进一步关注。
基金This research is supported by grants DK58379 and DK44442 from the USA National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health.
文摘Cholesterol 7 alpha-hydroxylase(CYP7A1,EC1.14)is the first and rate-limiting enzyme in the classic bile acid synthesis pathway.Much progress has been made in understanding the transcriptional regulation of CYP7A1 gene expression and the underlying molecular mechanisms of bile acid feedback regulation of CYP7A1 and bile acid synthesis in the last three decades.Discovery of bile acid-activated receptors and their roles in the regulation of lipid,glucose and energy metabolism have been translated to the development of bile acid-based drug therapies for the treatment of liver-related metabolic diseases such as alcoholic and non-alcoholic fatty liver diseases,liver cirrhosis,diabetes,obesity and hepatocellular carcinoma.This review will provide an update on the advances in our understanding of the molecular biology and mechanistic insights of the regulation of CYP7A1 in bile acid synthesis in the last 40 years.
