Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism....Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.展开更多
固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)是调节胆固醇,脂肪酸和甘油三酯生物合成的主要转录因子,控制着脂肪生成和摄取等关键基因的表达。笔者总结了SREBPs的激活机制及其与胰岛素、环磷腺苷、肝脏X...固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)是调节胆固醇,脂肪酸和甘油三酯生物合成的主要转录因子,控制着脂肪生成和摄取等关键基因的表达。笔者总结了SREBPs的激活机制及其与胰岛素、环磷腺苷、肝脏X受体等相互作用,共同参与脂质代谢的过程,并结合最新研究动态对SREBPs的功能进行阐述。这些发现表明,抑制SREBPs可以成为治疗代谢性疾病的新策略,如Ⅱ型糖尿病,胰岛素抵抗,脂肪肝、动脉粥样硬化以及相关肿瘤等。展开更多
骨关节炎是影响人类健康的重要退行性疾病之一,造成了大量的身体残疾和医疗资源支出,但是该病的具体发病机制尚未阐明,从而无法治愈该病。编码固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的基因是近年来...骨关节炎是影响人类健康的重要退行性疾病之一,造成了大量的身体残疾和医疗资源支出,但是该病的具体发病机制尚未阐明,从而无法治愈该病。编码固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的基因是近年来研究较多的基因,在维持机体脂质代谢稳态中起到重要的作用,越来越多的研究证实,该基因与骨关节炎关系密切。该文将会从SREBPs基因介绍、SREBPs基因与骨关节炎的关系及其通过相关因子作用造成机体代谢障碍及骨关节炎的可能机制方面进行相关探讨,就SREBPs基因在骨关节炎中的作用作一综述,从而为相关研究提供便利。展开更多
基金Supported by The Natural Sciences and Engineering Research Council of Canada,No.NSERC 7594
文摘Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.
文摘固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)是调节胆固醇,脂肪酸和甘油三酯生物合成的主要转录因子,控制着脂肪生成和摄取等关键基因的表达。笔者总结了SREBPs的激活机制及其与胰岛素、环磷腺苷、肝脏X受体等相互作用,共同参与脂质代谢的过程,并结合最新研究动态对SREBPs的功能进行阐述。这些发现表明,抑制SREBPs可以成为治疗代谢性疾病的新策略,如Ⅱ型糖尿病,胰岛素抵抗,脂肪肝、动脉粥样硬化以及相关肿瘤等。
文摘骨关节炎是影响人类健康的重要退行性疾病之一,造成了大量的身体残疾和医疗资源支出,但是该病的具体发病机制尚未阐明,从而无法治愈该病。编码固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的基因是近年来研究较多的基因,在维持机体脂质代谢稳态中起到重要的作用,越来越多的研究证实,该基因与骨关节炎关系密切。该文将会从SREBPs基因介绍、SREBPs基因与骨关节炎的关系及其通过相关因子作用造成机体代谢障碍及骨关节炎的可能机制方面进行相关探讨,就SREBPs基因在骨关节炎中的作用作一综述,从而为相关研究提供便利。
基金the Research and Development Projects of Shenzhen,No.JCYJ20130402114702130the Program of Shenzhen Municipal Science and Technology Bureau,No.201302064~~