共查询到19条相似文献,搜索用时 234 毫秒
1.
脂联素调节糖脂代谢相关信号通路的研究进展 总被引:1,自引:0,他引:1
脂联素是一种主要由脂肪组织分泌的脂肪细胞因子,具有调节糖脂代谢、增强胰岛素敏感性、抗炎和抗动脉粥样硬化等多种作用。在脂联素介导的信号通路中,脂联素首先与脂联素受体(AdipoR)位于膜外的羧基端结合,再通过AdipoR膜内的氨基端与信号接头蛋白结合,进而激活下游的多条信号通路,其中腺苷酸活化蛋白激酶(AMPK)是脂联素信号通路中的关键分子,活化的AMPK可以使其下游的乙酰辅酶A羧化酶(ACC)、p38丝裂原活化蛋白激酶(p38 MAPK)、磷脂酰肌醇3激酶(PI3K)等多种胞质信号分子磷酸化,介导细胞能量代谢。本文重点综述了脂联素通过AMPK调节糖脂代谢的信号通路的研究进展。 相似文献
2.
脂联素在炎症性疾病中的研究进展 总被引:1,自引:0,他引:1
脂肪组织不仅是一个被动的能量储存的器官,它还是一个调节机体内分泌、能量代谢及炎症的内分泌器官.脂联素是由Scherer等于1995年在小鼠3T3-L1前脂肪细胞系的分化过程中分离克隆发现的主要由脂肪细胞分泌的一种内源性生物活性蛋白质.目前的研究表明脂联素具有抑制动脉粥样硬化、保护心血管系统、改善胰岛素抵抗、调节脂质代谢及抗炎等多种功能.现就脂联素的结构、基因表达调控以及它在动脉粥样硬化、心脏疾病、脂质代谢等肥胖引起的慢性炎症性疾病和自身免疫性疾病(如类风湿性关节炎,系统性红斑狼疮,克罗恩病)及急性肝炎等急性炎症性疾病中的作用作一综述.系统地介绍脂联素在各种炎症性疾病中发挥效用的机制,更好地认识脂联素的作用机理,为以后介入脂联素作用的调节过程、开发研究新药物等后续研究打下良好的基础. 相似文献
3.
4.
5.
脂肪细胞因子是心血管并发症的重要调节因子.其中,脂联素是脂肪细胞分泌的重要血管保护因子.肥胖、糖尿病及冠心病患者脂联素水平显著降低,低脂联素血症是动脉粥样硬化发生发展的独立危险因素.脂联素既可直接抑制动脉粥样硬化灶的形成,亦可通过间接作用抑制动脉粥样硬化的形成.脂联素在动脉粥样硬化的防治方面有明显的应用前景. 相似文献
6.
7.
8.
9.
脂联素作为脂肪细胞产生和分泌的一种细胞因子,在细胞和动物的基础实验中,脂联素已被证实具有胰岛素增敏、抗炎、抗氧化、抗动脉粥样硬化和抗凋亡等作用。然而在大规模人群的流行病学和基因组学的研究中,脂联素的这些有益作用却不能够完全再现。该文将对循环中脂联素水平与2型糖尿病、心血管疾病矛盾性关系进行归纳与总结,并对其矛盾性关系的原因给予阐述及分析,旨在为今后进一步研究脂联素在2型糖尿病及心血管疾病中的作用提供科学依据。 相似文献
10.
脂联素是人和动物体内重要的内源性生物活性激素,具有改善胰岛素抵抗、调控脂类代谢、抗动脉粥样硬化、保护心脏、抗炎、抗氧化应激、抗纤维化以及调控细胞凋亡等作用。脂联素需要与其受体结合才能发挥生物学功能,但因其结构和浓度的影响,脂联素在临床上的应用受到一定程度限制。研究发现,多种脂联素受体激动剂通过激活脂联素受体发挥与脂联素相似的生物学功能,且脂联素受体激动剂多为人工合成的小分子或筛选的多肽,作用效果更加明确。本文整理了目前已经报道的脂联素受体激动剂及其研究进展,概述了脂联素受体激动剂对肝脏、肾脏、心脏、血管、眼和皮肤等相关器官或组织疾病的作用或影响,为开发以脂联素及其受体为靶点的治疗药物提供理论依据。 相似文献
11.
Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions 总被引:3,自引:0,他引:3
Yamauchi T Nio Y Maki T Kobayashi M Takazawa T Iwabu M Okada-Iwabu M Kawamoto S Kubota N Kubota T Ito Y Kamon J Tsuchida A Kumagai K Kozono H Hada Y Ogata H Tokuyama K Tsunoda M Ide T Murakami K Awazawa M Takamoto I Froguel P Hara K Tobe K Nagai R Ueki K Kadowaki T 《Nature medicine》2007,13(3):332-339
Adiponectin plays a central role as an antidiabetic and antiatherogenic adipokine. AdipoR1 and AdipoR2 serve as receptors for adiponectin in vitro, and their reduction in obesity seems to be correlated with reduced adiponectin sensitivity. Here we show that adenovirus-mediated expression of AdipoR1 and R2 in the liver of Lepr(-/-) mice increased AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor (PPAR)-alpha signaling pathways, respectively. Activation of AMPK reduced gluconeogenesis, whereas expression of the receptors in both cases increased fatty acid oxidation and lead to an amelioration of diabetes. Alternatively, targeted disruption of AdipoR1 resulted in the abrogation of adiponectin-induced AMPK activation, whereas that of AdipoR2 resulted in decreased activity of PPAR-alpha signaling pathways. Simultaneous disruption of both AdipoR1 and R2 abolished adiponectin binding and actions, resulting in increased tissue triglyceride content, inflammation and oxidative stress, and thus leading to insulin resistance and marked glucose intolerance. Therefore, AdipoR1 and R2 serve as the predominant receptors for adiponectin in vivo and play important roles in the regulation of glucose and lipid metabolism, inflammation and oxidative stress in vivo. 相似文献
12.
13.
Adiponectin and its receptors, AdipoR1 and AdipoR2, regulate glucose and fatty acid metabolism partly via activation of AMP-activated protein kinase (AMPK). Recent work in Nature Medicine (Holland et al., 2011) suggests that adiponectin stimulates ceramidase activity through AdipoR1 and AdipoR2, an activity potentially involved in promoting cell survival. 相似文献
14.
《Cell Adhesion & Migration》2013,7(3):358-362
Adiponectin is an adipocytokine involved in the pathogenesis of various obesity-related disorders. Also, it has been shown that adiponectin has therapeutic potential for metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. Adiponectin can modulate breast cancer cell growth and proliferation. Anti-metastatic effects of adiponectin have also been elucidated. It has been shown that adiponectin inhibits important metastatic properties such as adhesion, invasion and migration of breast cancer cells. Examination of the underlying molecular mechanisms has shown that adiponectin treatment increases AMP-activated protein kinase (AMPK) phosphorylation and activity. Adiponectin also increases phosphorylation of downstream target of AMPK, Acetyl-CoA Carboxylase (ACC) and decreases phosphorylation of p70S6 kinase (S6K). Importantly, adiponectin treatment increases the expression of tumor suppressor gene, LKB1 in breast cancer cells. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, its biological functions including inhibition of adhesion, migration and invasion of breast cancer cells. Although further studies are required to analyze the effect of adiponectin on LKB1-AMPK-S6K axis, these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. These results highlight a new role for LKB1 in adiponectin action and may have significant implication for development of novel therapeutic options. 相似文献
15.
AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart 总被引:6,自引:0,他引:6
Myocardial ischemia is the leading cause of all cardiovascular deaths in North America. Myocardial ischemia is accompanied by profound changes in metabolism including alterations in glucose and fatty acid metabolism, increased uncoupling of glucose oxidation from glycolysis and accumulation of protons within the myocardium. These changes can contribute to a poor functional recovery of the heart. One key player in the ischemia-induced alteration in fatty acid and glucose metabolism is 5'AMP-activated protein kinase (AMPK). Accumulating evidence suggest that activation of AMPK during myocardial ischemia both increases glucose uptake and glycolysis while also increasing fatty acid oxidation during reperfusion. Gain-of-function mutations of AMPK in cardiac muscle may also be causally related to the development of hypertrophic cardiomyopathies. Therefore, a better understanding of role of AMPK in cardiac metabolism is necessary to appropriately modulate its activity as a potential therapeutic target in treating ischemia reperfusion injuries. This review attempts to update some of the recent findings that delineate various pathways through which AMPK regulates glucose and fatty acid metabolism in the ischemic myocardium. 相似文献
16.
AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that is a key regulator of energy balance at both the cellular and whole-body level. AMPK acts to stimulate ATP production and reduce ATP consumption when cellular ATP levels fall, thereby normalizing energy balance. Given the central role of AMPK in cellular carbohydrate and lipid metabolism, AMPK activation has been proposed to be a therapeutic target for conditions associated with dysfunctional nutrient metabolism including obesity, type 2 diabetes, hepatic steatosis, cardiovascular diseases and cancer. One way by which increased ATP production can be achieved is by increasing the supply of nutrient substrates. In the 1990s, AMPK activation was demonstrated to stimulate glucose uptake in striated muscle, thereby improving substrate supply for ATP production. Subsequently AMPK activation was postulated to underlie the increase in glucose uptake that occurs during muscle contraction. More recently, however, several lines of evidence have demonstrated that AMPK activation is unlikely to be required for contraction-mediated glucose uptake. Furthermore, despite the importance of AMPK in cellular and whole-body metabolism, far fewer studies have investigated either the role of AMPK in glucose uptake by non-muscle tissues or whether AMPK regulates the uptake of fatty acids. In the present review, we discuss the role of AMPK in nutrient uptake by tissues, focusing on glucose uptake out with muscle and fatty acid uptake. 相似文献
17.
Adiponectin-mediated modulation of hypertrophic signals in the heart 总被引:31,自引:0,他引:31
Shibata R Ouchi N Ito M Kihara S Shiojima I Pimentel DR Kumada M Sato K Schiekofer S Ohashi K Funahashi T Colucci WS Walsh K 《Nature medicine》2004,10(12):1384-1389
Patients with diabetes and other obesity-linked conditions have increased susceptibility to cardiovascular disorders. The adipocytokine adiponectin is decreased in patients with obesity-linked diseases. Here, we found that pressure overload in adiponectin-deficient mice resulted in enhanced concentric cardiac hypertrophy and increased mortality that was associated with increased extracellular signal-regulated kinase (ERK) and diminished AMP-activated protein kinase (AMPK) signaling in the myocardium. Adenovirus-mediated supplemention of adiponectin attenuated cardiac hypertrophy in response to pressure overload in adiponectin-deficient, wild-type and diabetic db/db mice. In cultures of cardiac myocytes, adiponectin activated AMPK and inhibited agonist-stimulated hypertrophy and ERK activation. Transduction with a dominant-negative form of AMPK reversed these effects, suggesting that adiponectin inhibits hypertrophic signaling in the myocardium through activation of AMPK signaling. Adiponectin may have utility for the treatment of hypertrophic cardiomyopathy associated with diabetes and other obesity-related diseases. 相似文献
18.
Jarzyna R 《Postepy biochemii》2006,52(3):283-288
AMP-activated protein kinase (AMPK) is the central component of a protein kinase cascade that acts as an energy sensor maintaining the energy balance at the cellular as well as at the whole body level. Within the healthy cell, metabolic stress leading to an increase in AMP concentration results in AMPK activation. Once activated, AMPK "switches off" many anabolic pathways e.g. fatty acid and protein synthesis while "switches on" catabolic pathways such as fatty acid oxidation or glycolysis which serve to restore intracellular ATP level. Adipocyte derived hormones leptin and adiponectin activate AMPK in peripheral tissues increasing energy expenditure. AMPK also regulates food intake due to response to hormonal and nutrient signals in hypothalamus. Antidiabetic drugs that mimic the action of insulin activate the AMPK signaling pathways. Further studies are needed to clarify the importance of the AMPK activation for therapeutic effects of this drugs. 相似文献
19.
Motoharu Awazawa Kohjiro Ueki Kazunori Inabe Kazuma Kaneko Nabeel Bardeesy Ryozo Nagai 《Biochemical and biophysical research communications》2009,382(1):51-2811
Adiponectin, one of the insulin-sensitizing adipokines, has been shown to activate fatty acid oxidation in liver and skeletal muscle, thus maintaining insulin sensitivity. However, the precise roles of adiponectin in fatty acid synthesis are poorly understood. Here we show that adiponectin administration acutely suppresses expression of sterol regulatory element-binding protein (SREBP) 1c, the master regulator which controls and upregulates the enzymes involved in fatty acid synthesis, in the liver of +Leprdb/+Leprdb (db/db) mouse as well as in cultured hepatocytes. We also show that adiponectin suppresses SREBP1c by AdipoR1, one of the functional receptors for adiponetin, and furthermore that suppressing either AMP-activated protein kinase (AMPK) via its upstream kinase LKB1 deletion cancels the negative effect of adiponectin on SREBP1c expression. These data show that adiponectin suppresses SREBP1c through the AdipoR1/LKB1/AMPK pathway, and suggest a possible role for adiponectin in the regulation of hepatic fatty acid synthesis. 相似文献