脂联素的研究进展

脂联素（adiponectin）是一种由脂肪细胞特异性高分泌,具有多种生物学功能的特殊蛋白质它直接作用于肝脏、骨骼肌和血管,能提高胰岛素敏感性,增强脂肪酸β氧化,抵制血管炎症反应,最新研究还发现脂联素和骨生成密切相关。与其它脂肪因子不同的是,循环中脂联素的浓度与人体脂肪含量成反比,会因TNF-α的作用而上调,会被噻唑烷二酮类药物所抑制,还受到胰岛素抵抗和炎症反应的影响脂联素受体有2类,分别为AdipoR1和AdipoR2,AdipoR1主要分布在骨骼肌上,AdipoR2则高表达于肝脏组织。本文主要综述了脂联素及其受体的结构、生物学功能和研究进展。     

西伯利亚鲟AdipoR克隆、组织分布及其对禁食的响应

为了探究西伯利亚鲟脂联素受体的表达特征及其对能量状态变化的响应,研究采用RACE方法克隆获得AdipoR1和AdipoR2的cDNA全长.西伯利亚鲟AdipoR1 cDNA全长为2013 bp,开放阅读框为1146 bp;AdipoR2 cDNA全长为1590 bp,开放阅读框为1086 bp.多重序列比对结果显示,西...     

大鼠胰岛素抵抗形成中脂联素受体基因表达及运动的影响

目的:检测SD大鼠脂联素受体的分布,观察大鼠胰岛素抵抗(IR)形成中脂联素受体(Adipok)基因表达及运动的影响。方法:46只雄性SD大鼠随机分为4组(n=12),以高脂膳食喂养诱导IR,同时运动组实施10周游泳运动干预。结果:AdipoR1/R2mRNA分别在骨骼肌和肝脏高表达(P<0.05);H组骨骼肌AdipoR1和肝脏AdipoR2mRNA表达显著低于C组(P<0.05)。结论:骨骼肌和肝脏AdipoR1/R2mRNA表达的下调可能是高脂大鼠IR形成的机制之一,未观察到运动干预的显著影响。     

脂联素及其受体抗肿瘤的研究进展

目前大量的研究已表明循环系统的脂联素浓度与恶性肿瘤的发病风险呈负相关。这些恶性肿瘤包括绝经后乳腺癌、子宫内膜癌、大肠癌、前列腺癌等。脂联素是在其受体(AdipoR1和AdipoR2)的介导下发挥其生物学作用。相关实验发现,AdipoR1/R2在乳腺癌、子宫内膜癌、结直肠癌等肿瘤组织中有表达。因此针对脂联素的研究可能揭示其与恶性肿瘤的发生、发展的相关性。     

脂联素的研究进展

脂联素(adiponectin)是一种由脂肪细胞特异性高分泌,具有多种生物学功能的特殊蛋白质.它直接作用于肝脏、骨骼肌和血管,能提高胰岛素敏感性,增强脂肪酸β氧化,抵制血管炎症反应,最新研究还发现脂联素和骨生成密切相关.与其它脂肪因子不同的是,循环中脂联素的浓度与人体脂肪含量成反比,会因TNF-α的作用而上调,会被噻唑烷二酮类药物所抑制,还受到胰岛素抵抗和炎症反应的影响.脂联素受体有2类,分别为AdipoR1和AdipoR2,AdipoR1主要分布在骨骼肌上,AdipoR2则高表达于肝脏组织.本文主要综述了脂联素及其受体的结构、生物学功能和研究进展.     

脂联素调节糖脂代谢相关信号通路的研究进展

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。     

脂联素的信号转导通路

脂联素是一种由脂肪组织分泌的胶原样蛋白,其能降低血浆游离脂肪酸,具有抗动脉粥样硬化、改善胰岛素抵抗、降血糖、抗炎等作用,但其作用机制尚不十分明确。近期,脂联素的两型受体AdipoR1／R2已经被克隆,脂联素可能是通过其受体激活过氧化物酶体增殖物激活受体(PPAR)和AMPK信号转导通路而发挥作用。     

褪黑素受体激动剂改善高糖高脂喂养大鼠脂联素敏感性

目的观察褪黑素受体激动剂（NEU-P11）对高糖高脂饲养大鼠脂联素敏感性的影响。方法将30只SD大鼠随机分为对照组（CD组）,高糖高脂组（HFSD组）,褪黑素组（Mel组）,褪黑素受体激动剂组（NEU-P11组）。CD组饲以正常饲料;其余3组饲以高糖高脂饲料。6个月后,给药治疗2个月。治疗期间,Mel组每天注射Mel（4mg／kg）;NEU—P11组每天注射NEU-P11（10mg／kg）;CD组以及HFSD组注射生理盐水（5ml／kg）。测定糖脂代谢指标并做口服葡萄糖耐量实验（oral glucose tolerant test,OG-TY）,Western印迹检测脂联素（adiponectin,APN）在脂肪组织及脂联素受体（AdipoR）在骨骼肌组织中的表达变化。结果高糖高脂饮食可诱导SD大鼠产生胰岛素抵抗,脂联素表达增加。Neu-P11治疗后,胰岛素敏感性增强．脂联素表达降低至正常水平。结论Neu-P11能提高胰岛素敏感性,改善脂联素抵抗。     

3脂联素受体表达调控的研究进展

脂联素是主要由脂肪细胞分泌的细胞因子,具有胰岛素增敏、抗炎、抗动脉粥样硬化和保护心肌等作用.脂联素的生物学效应需通过脂联素受体1/2的介导来完成.脂联素受体的表达水平直接影响到脂联素对下游信号通路的激活及生物学效应的发挥.对调节脂联素受体表达的因素进行研究,不但有助于揭示调控脂联素受体表达的分子机制,而且也为防治代谢紊乱和心血管疾病提供新思路.     

非诺贝特和二甲双胍对Zucker糖尿病大鼠脂联素受体表达的影响

脂联素是一种由脂肪细胞分泌的蛋白,可通过激活AMPK和PPAR-α等信号分子影响糖脂代谢,并具有胰岛素增敏作用。其生物学效应是由脂联素受体（adiponectin receptor,AdipoR）1和2介导的。研究发现,ob／ob和db／db小鼠及有2型糖尿病家族史的患者骨骼肌中AdipoR1的表达水平下降,又有研究表明两种受体介导了不同的生物学效应,提示脂联素的生物学作用受其受体表达水平及两种受体比例关系的影响。     

Expression of adiponectin receptors in pancreatic beta cells

Pancreatic beta cell dysfunction is an early and crucial pathogenic factor in the development of type 2 diabetes. Free fatty acids (FFA) and adipokines released from adipose tissues lead to both the development of insulin resistance and beta cell dysfunction. Adiponectin is a novel adipokine with antidiabetic properties. Its circulating concentrations are reduced in subjects with increased visceral adiposity, insulin resistance, or type 2 diabetes. Very recently, the cloning of two adiponectin receptors AdipoR1 and AdipoR2 was reported. AdipoR1 is abundantly expressed in muscle, while AdipoR2 is predominantly expressed in liver. Here we report the marked expression of mRNAs for the adiponectin receptors AdipoR1 and AdipoR2 in human and rat pancreatic beta cells, at levels similar to liver and greater than muscle. Adiponectin receptor expression is increased by beta cell exposure to the unsaturated FFA oleate, and treatment of insulin-producing cells with globular adiponectin induces lipoprotein lipase expression. Regulated adiponectin receptor expression on pancreatic beta cells might be a novel mechanism modulating the effects of circulating adiponectin.     

Effects of exercise on adiponectin and adiponectin receptor levels in rats

Adiponectin reportedly reduces insulin-resistance. Exercise has also been shown to lessen insulin-resistance, though it is not known whether exercise increases levels of adiponectin and/or its receptors or whether its effects are dependent on exercise intensity and/or frequency. Catecholamine levels have been shown to increase during exercise and to fluctuate based on exercise intensity and duration. In light of this information, we examined the effects of exercise on catecholamine, adiponectin, and adiponectin receptor levels in rats. Our data showed that blood adiponectin levels increased by 150% in animals that exercised at a rate of 30 m/min for 60 min 2 days per week, but not 5 days, per week; no such increase was observed in rats that exercised at a rate of 25 m/min for 30 min. The effects of exercise on adiponectin receptor mRNA were variable, with adiponectin receptor 1 (AdipoR1) levels in muscle increasing up to 4 times while adiponectin receptor 2 (AdipoR2) levels in liver fell to below half in response to exercise at a rate of 25 m/min for 30 min 5 days per week. We also observed that urinary epinephrine levels and plasma lipids were elevated by exercise at a rate of 25 m/min for 30 min 2 days per week. Exercise frequency at a rate of 25 m/min for 30 min correlated with AdipoR1 and AdipoR2 mRNA expression in the muscle and liver, respectively (r=0.640, p<0.05 and r=-0.808, p<0.0005, respectively). Urinary epinephrine levels correlated with AdipoR2 mRNA expression in liver tissues (r=-0.664, p<0.05) in rats that exercised at a rate of 25 m/min for 30 min. Thus, exercise may regulate adiponectin receptor mRNA expression in tissues, which might cause increases in glucose uptake and fatty acid oxidation in the muscle. The effect of exercise on adiponectin levels depends on the specific conditions of the exercise.     

Adiponectin receptor binding proteins - recent advances in elucidating adiponectin signalling pathways

Adiponectin whose systemic levels are reduced in obesity-related diseases ameliorates insulin sensitivity and regulates biological processes like apoptosis, proliferation, migration and inflammation. Adiponectin binds to adiponectin receptors, AdipoR1 and AdipoR2, which are ubiquitously expressed. Clathrin-dependent endocytosis of AdipoR1 and adiponectin has been demonstrated to modulate adiponectin bioactivity. Recently, APPL1 has been identified as an AdipoR1 and AdipoR2 binding protein. Furthermore, activated protein kinase C1, endoplasmic reticulum protein 46 and protein kinase CK2β subunit form a complex with AdipoR1. This review summarizes recent studies exploiting heterologous expression of adiponectin receptors in yeast, and the type and function of the recently described adiponectin receptor associated proteins.     

Reduced response to adiponectin and lower abundance of adiponectin receptor proteins in type 2 diabetic monocytes

The abundance of the adiponectin receptors, AdipoR1 and AdipoR2, and the effects of the antidiabetic adipokine adiponectin in monocytes of normal-weight and overweight controls and type 2 diabetic patients (T2D) were analyzed. AdipoR1 and AdipoR2 mRNAs were increased in monocytes of obese controls and T2D patients when compared to normal-weight controls, and AdipoR1 mRNA positively correlated to AdipoR2 mRNA, the waist to hip ratio and systemic adiponectin. However, AdipoR1 and AdipoR2 proteins were lower in monocytes of T2D compared to normal-weight donors. Induction of IL-6 and IL-8 by adiponectin, an effect involving p38 MAPK, was also reduced in T2D monocytes.     

Receptor for activated C-kinase 1, a novel binding partner of adiponectin receptor 1

Adiponectin is an adipose tissue derived hormone with anti-diabetic and insulin-sensitizing properties. Two adiponectin receptors, AdipoR1 and AdipoR2, have recently been identified, yet the signaling pathways triggered through adiponectin receptors remain to be elucidated. Using a yeast two-hybrid screen, we identified an adaptor protein, receptor for activated protein kinase C1 (RACK1), as an interacting partner of human AdipoR1. RACK1 was confirmed to interact with AdipoR1 by co-immunoprecipitation and co-localization analysis in mammalian cells. The interaction was enhanced by adiponectin stimulation. In addition, the knockdown of RACK1 by RNA interference inhibited adiponectin-stimulated glucose uptake in HepG2 cells. These results suggest that RACK1 may act as a key bridging factor in adiponectin signaling transduction through interacting with AdipoR1.     

Aberrant expressions of leptin and adiponectin receptor isoforms in chronic myeloid leukemia patients

Background

Leptin and adiponectin receptors mediate the role of leptin in stimulating the growth of leukemic cells and the protective function of adiponectin undertaken in several malignancies such as leukemia. In this study, we investigated the involvement of the expression of leptin and adiponectin receptors in chronic myeloid leukemia (CML) pathogenesis.

Methods

The expression of leptin receptor isoforms, OB-Rt, OB-Ra, and OB-Rb, and the expression of adiponectin receptors, AdipoR1 and AdipoR2, were measured as mRNA levels in two CML cell lines (K562 and Meg-01) and 20 CML patients and 24 healthy controls by using RT-PCR.

Results

OB-Rt and OB-Ra isoforms expression of the leptin receptors were found to be significantly lower in Meg-01 cell lines than K562 cells. All leptin receptors were downregulated in CML patients and more particularly OB-Rb level was found to be undetectably low in normal PBMC as well as in CML patients. AdipoR1 expression level was higher in Meg-01 than in K562, whereas AdipoR2 level was found to be unchanged in both cell lines. Interestingly, while AdipoR1 expression increased in CML patients, AdipoR2 decreased. Moreover, imatinib therapy did not affect both leptin and adiponectin isoform expressions.

Conclusion

While the decrease in leptin receptor levels in CML patients was confirmed, the increase in AdipoR1 levels and relevant decrease in AdipoR2 levels depicted their possible involvement in CML pathogenesis. This suggests different functions of adiponectin receptors in CML development.     

Changes in the gene expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in ovarian follicular cells of dairy cow at different stages of development

Adiponectin is one of the most important, recently discovered adipocytokines that acts at various levels to control male and female fertility through central effects on the hypothalamus-pituitary axis or through peripheral effects on the ovary, uterus, and embryo. We studied simultaneous changes in the gene expression pattern of adiponectin and adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) in granulosa and theca cells, cumulus-oocyte complex, and in corpus luteum in healthy bovine (Bos tarus) follicles at different stages of development. The expression levels of adiponectin, AdipoR1, and AdipoR2 mRNA were lower (P < 0.05) in granulosa and cumulus cells in comparison with that in theca cells and oocyte. In contrast with the oocyte, AdipoR1 in granulosa, theca, and luteal cells was expressed (P < 0.05) more than AdipoR2. Adiponectin expression increased (P < 0.05) in granulosa cells and in cumulus-oocyte complex during follicular development from small to large follicles. Opposite results were observed in theca cells. Expression of adiponectin was highest in the late stages of corpus luteum (CL) regression, whereas lower expression was recorded in active CL (P < 0.05). AdipoR1 and AdipoR2 expression increased during the terminal follicular growth in granulosa and theca cells (P < 0.05) and during the luteal phase progress in CL. There was positive correlation between adiponectin mRNA level in granulosa cells from large follicles and follicular fluid estradiol concentration (r = 0.48, P < 0.05) and negative correlation between adiponectin mRNA abundance in theca cells and follicular fluid progesterone concentration (r = -0.44, P < 0.05). In conclusion, we found that the physiologic status of the ovary has significant effects on the natural expression patterns of adiponectin and its receptors in follicular and luteal cells of bovine ovary.