ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling

The pleiotropic effects of the insulin-sensitizing adipokine adiponectin are mediated, at least in part, by two seven-transmembrane domain receptors AdipoR1 and AdipoR2. Recent reports indicate a role for AdipoR-binding proteins, namely APPL1, RACK1 and CK2β, in proximal signal transduction events. Here we demonstrate that endoplasmic reticulum protein 46 (ERp46) interacts specifically with AdipoR1 and provide evidence that ERp46 modulates adiponectin signalling. Co-immunoprecipitation followed by mass spectrometry identified ERp46 as an AdipoR1-, but not AdipoR2-, interacting protein. Analysis of truncated constructs and GST-fusion proteins revealed the interaction was mediated by the cytoplasmic, N-terminal residues (1-70) of AdipoR1. Indirect immunofluorescence microscopy and subcellular fractionation studies demonstrated that ERp46 was present in the ER and the plasma membrane (PM). Transient knockdown of ERp46 increased the levels of AdipoR1, and AdipoR2, at the PM and this correlated with increased adiponectin-stimulated phosphorylation of AMPK. In contrast, adiponectin-stimulated phosphorylation of p38MAPK was reduced following ERp46 knockdown. Collectively these results establish ERp46 as the first AdipoR1-specific interacting protein and suggest a role for ERp46 in adiponectin receptor biology and adiponectin signalling.     

High glucose/High Lipids impair vascular adiponectin function via inhibition of caveolin-1/AdipoR1 signalsome formation

Reduced levels of adiponectin (APN) contribute to cardiovascular injury in the diabetic population. Recent studies demonstrate elevated circulating APN levels are associated with endothelial dysfunction during pre-diabetes, suggesting the development of APN resistance. However, mechanisms leading to, and the role of, vascular APN resistance in endothelial dysfunction remain unidentified. The current study determined whether diabetes cause endothelial APN resistance, and by what mechanisms. Under high glucose/high lipids (HG/HL), APN-stimulated nitric oxide production by HUVEC was decreased, phosphorylation of eNOS, AMPK, and Akt was attenuated (P<0.01), and APN's anti-TNFα effect was blunted (P<0.01). APN receptor expression remained normal, whereas Cav1 expression was reduced in HG/HL cells (P<0.01). The AdipoR1/Cav1 signaling complex was dissociated in HG/HL cells. Knock-down of Cav1 inhibited APN's anti-oxidative and anti-inflammatory actions. Conversely, preventing HG/HL-induced Cav1 downregulation by Cav1 overexpression preserved APN signaling in HG/HL cells. Knock-in of a wild type Cav1 in Cav1 knock-down cells restored caveolae structure and rescued APN signaling. In contrast, knock-in of a mutated Cav1 scaffolding domain restored caveolae structure, but failed to rescue APN signaling in Cav1 knock-down cells. Finally, AdipoR1/Cav1 interaction was significantly reduced in diabetic vascular tissue, and the vasorelaxative response to APN was impaired in diabetic animals. The current study demonstrates for the first time the interaction between AdipoR1 and Cav1 is critical for adiponectin-mediated vascular signaling. The AdipoR1/Cav1 interaction is adversely affected by HG/HL, due largely to reduced Cav1 expression, supporting a potential mechanism for the development of APN resistance, contributing to diabetic endothelial dysfunction.     

Diacylglycerol kinase alpha regulates globular adiponectin-induced reactive oxygen species

Abstract:

It has previously been reported that the globular form of adiponectin (gAd), mature adipocyte-derived cytokine, induced generation of reactive oxygen species (ROS) and nitric oxide (NO) in the murine macrophage cell line RAW 264. This study investigated whether diacylglycerol kinases (DGKs), enzymes functioning in sub-cellular signalling pathways, had a role on gAd-induced ROS generation in RAW 264 cells. Administration of R59022, a specific inhibitor for DGK, reduced gAd-induced ROS generation and NO release. RAW 264 cell expressed DGKα mRNA. Depression of DGKα mRNA by RNA interference significantly reduced the ROS generation in response to gAd treatment. Interestingly, transfection with the DGKα-specific small interfering RNA attenuated the expression level of Nox1 mRNA in gAd-treated RAW 264 cells. In addition, the DGKα knockdown with siRNA suppressed gAd-induced NO release.     

脓毒症患者血清TOLL样受体4、脂联素与炎症反应和病情严重程度的关系

目的:探讨脓毒症患者血清TOLL样受体4(TLR4)、脂联素(APN)与炎症反应和病情严重程度的关系。方法:选取2016年12月到2018年4月期间在重庆市中医院接受治疗的脓毒症患者60例作为研究组,另选取同期本院健康体检者60例作为对照组。根据急性生理及慢性健康状况Ⅱ(APACHEⅡ)评分将脓毒症患者分为高分组17例(APACHEⅡ评分≥20分)和低分组43例(APACHEⅡ评分20分)。比较两组血清中的TLR4、APN、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)水平,比较高分组和低分组患者血清中的TLR4、APN及炎症因子水平,分析脓毒症患者TLR4、APN的表达与炎症因子、APACHEⅡ评分的相关性。结果:研究组血清中的TLR4、PCT、TNF-α、CRP水平均明显高于对照组,APN水平明显低于对照组(P0.05)。高分组患者血清中的TLR4、PCT、TNF-α、CRP水平明显高于低分组,APN水平明显低于低分组(P0.05)。脓毒症患者TLR4的表达与PCT、TNF-α、CRP、APACHEⅡ评分呈正相关,APN的表达与PCT、TNF-α、CRP、APACHEⅡ评分呈负相关(P0.05)。结论:脓毒症患者病情越严重,TLR4水平越高,而APN水平越低,TLR4、APN可能是通过调节炎症反应来影响脓毒症患者的疾病进展。     

脂联素在早产儿血清中的表达及其与体格指标、载脂蛋白和骨密度的关系

目的:探讨脂联素在早产儿血清中的表达水平及其与体格指标、载脂蛋白和骨密度的相关性。方法:选择2017年1月至2018年5月期间我院新生儿科住院的早产儿72例作为研究组,另外选择同期我院出生的足月新生儿58例作为对照组。对比两组新生儿的一般资料、脂联素、载脂蛋白和骨密度水平,分析早产儿血清脂联素水平与体格指标、载脂蛋白和骨密度的相关性,同时分析影响血清脂联素水平的危险因素。结果:两组受试新生儿的性别、胸围、低密度脂蛋白(LDL-C)及高密度脂蛋白(HDL-C)之间的差异无统计学意义(P0.05);研究组新生儿的胎龄、体质量指数(BMⅠ)、身长、头围、总胆固醇(TC)及三酰甘油(TG)明显低于对照组(P0.05);与对照组相比,研究组新生儿血清脂联素、载脂蛋白A-Ⅰ(Apo A-Ⅰ)及左胫骨中段超声波在骨骼中的传播速度(SOS)水平明显下降,而载脂蛋白B(Apo B)和Apo B/Apo A-Ⅰ水平均显著升高,且差异均具有统计学意义(P0.05);早产儿血清脂联素水平与胎龄、BMⅠ、头围、TC、TG、Apo A-Ⅰ及SOS呈正相关(P0.05),与Apo B和Apo B/Apo A-Ⅰ水平呈负相关(P0.05);Logistic回归结果显示,胎龄、BMⅠ、Apo B/Apo A-Ⅰ及SOS是早产儿血清脂联素水平的影响因素(P0.05)。结论:早产儿血清脂联素水平低于足月儿,血清脂联素水平与体格指标、载脂蛋白及骨密度密切相关,可能对新生儿的生长发育具有重要的调节作用。     

Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels.

Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC.

Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan.

Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels.

Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.     

血清脂联素水平对老年维持性血液透析患者心脑血管事件发生风险及预后的影响

目的:探讨老年维持性血液透析(MHD)患者血清脂联素(adiponectin,ADPN)水平与其心脑血管事件发生风险及其预后的关系。方法:采用酶联免疫吸附实验(ELISA)检测76例老年MHD患者血清ADPN水平,以5 mg/L为界,以5 mg/L为低ADPN组,≥5 mg/L为高ADPN组。随访观察两组心脑血管事件的发生情况及预后。采用Cox回归分析血清ADPN水平和心脑血管事件对老年MHD患者的预后影响。结果:76例老年MHD患者的血清ADPN水平为(11.10±10.68)mg/L,其中低ADPN组患者有33例,高ADPN组患者有43例。与低ADPN组相比,高ADPN组患者的心脑血管事件发生率明显下降,而生存时间明显延长(P0.05)。Cox回归分析显示低ADPN水平和发生心脑血管事件是老年MHD患者生存时间的危险因素(P0.05)。结论:血清ADPN水平可作为老年MHD患者心脑血管事件的预测指标,并与患者的预后相关,有较好的临床应用价值。