Diabetes,inflammation, and the adiponectin paradox: Therapeutic targets in SARS-CoV-2

Aging and pre-existing conditions in older patients increase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severity and its complications, although the causes remain unclear. Apart from acute pulmonary syndrome, Coronavirus 2019 (COVID-19) can increasingly induce chronic conditions. Importantly, SARS-CoV-2 triggers de novo type 2 diabetes mellitus (T2DM) linked to age-associated cardiovascular disease (CVD), cancers, and neurodegeneration. Mechanistically, SARS-CoV-2 induces inflammation, possibly through damage-associated molecular pattern (DAMP) signaling and ‘cytokine storm,’ causing insulin resistance and the adiponectin (APN) paradox, a phenomenon linking metabolic dysfunction to chronic disease. Accordingly, preventing the APN paradox by suppressing APN-related inflammatory signaling might prove beneficial. A better understanding could uncover novel therapies for SARS-CoV-2 and its chronic disorders.     

糖代谢异常患者脂联素水平与颈动脉内膜-中层厚度的关系

目的探讨糖代谢异常患者脂联素(adiponectin,APN)水平与颈动脉内膜-中层厚度(carotid intimal-medial thickness,CIMT)之间的关系。方法选取糖耐量正常30例、糖耐量减低36例、2型糖尿病36例,收集相关临床资料,应用酶联免疫法测定空腹血清APN,免疫散射比浊法测定血清超敏C-反应蛋白(high sensitivity C reactive protein,hs-CRP)。分析血清ANP和hs-CRP水平与CIMT的关系。结果从糖耐量正常、糖耐量低减至糖尿病,随着糖代谢异常的加重,APN逐渐降低,hs-CRP逐渐升高,CIMT逐渐增厚(P<0.05或0.01);以APN为因变量、各指标为自变量进行Pearson相关分析,甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)、hs-CRP和CIMT与APN水平呈负相关,高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)与APN水平呈正相关。结论APN水平下降与糖代谢异常患者动脉粥样硬化关系密切。     

Glucose Tolerance in Women 24 h Postpartum Is Related to Blood Pressure,Anthropometric Data,and Adipokine Serum Levels

Objectives. To characterize glucose tolerance and adipokine serum levels in a cohort of women shortly after delivery. Study Design. A study population of healthy pregnant women (n = 65) was invited to undergo a standardized oral glucose tolerance test within 24 h after delivery at the University Hospital of Leipzig. As controls, 30 nonpregnant healthy, lean women were studied. Glucose, insulin, proinsulin, c-peptide, leptin, adiponectin, and soluble leptin receptor levels were compared in cases and controls by using the Mann–Whitney U two-sample statistics and correlation according to Spearman. Results. As compared to normal glucose tolerant (NGT) women postpartum, fasting c-peptide levels were significantly higher (NGT mothers = 0.23 nmol/L, controls: 0.49 nmol/L, p < 0.001), whereas proinsulin serum levels were significantly lower in nonpregnant controls (NGT mothers = 1.37 pmol/L, controls = 1.00 pmol/L, p = 0.05). Considering fasting adiponectin values, postpartum adiponectin was significantly decreased compared with controls (NGT mothers = 6.9 μg/L, controls = 8.9 μg/L, p = 0.05). Fasting serum levels of leptin (NGT mothers = 17 ng/mL, controls = 10.6 ng/mL, p < 0.009) and soluble leptin receptor (NGT mothers = 34.4 ng/mL, controls = 17.7 ng/mL, p < 0.001) were increased postpartum. Conclusion. We found significantly lower adiponectin and higher leptin sera levels in women postpartum as compared to nonpregnant women. In addition, adipokine serum levels shortly after delivery were related to parameters of adiposity and glucose tolerance. We hypothesize that women in the post-delivery period exhibit biochemical features resembling metabolic syndrome, impaired glucose tolerance, and derangement of the adipokine system.     

Hypotensive effects of omentin-1 related to increased adiponectin and decreased interleukin-6 in intra-thoracic pericardial adipose tissue

BackgroundOmentin is an adipokine expressed in visceral adipose tissue (VAT). In vitro studies demonstrated that omentin induces vasorelaxation in isolated rat mesenteric arteries, and in vivo studies showed inhibition of agonist-induced increases in blood pressure, possibly mediated by nitric oxide (NO)-dependent mechanisms.MethodsWe investigated, in normotensive rats, the effects of subacute omentin-1 administration [8 μg/kg, intraperitoneally (ip), once daily for 14 days] on cardiac activity, blood pressure, plasma concentration of l-citrulline (as a marker of NO production from l-arginine), and the gene expression of adiponectin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in intra-thoracic pericardial adipose tissue (PAT). Electrocardiography (ECG), heart rate (HR), mean blood pressure (MBP), pulse pressure (PP) were monitored before and after treatment with omentin-1 or vehicle.ResultsWith respect to baseline and vehicle, we found a significant decrease of MBP (p < 0.005) and PP (p < 0.05) after treatment with omentin-1, while ECG and HR were not modified. Omentin-1 significantly increased l-citrulline levels in plasma (p < 0.05), and the gene expression of adiponectin in PAT (p < 0.05). On the other hand, we found decreased gene expression of IL-6 (p < 0.005), while TNF-α mRNA in PAT was not affected.ConclusionWe conclude that the hypotensive effects of omentin-1 could be driven by stimulated production of NO in the vascular system, possibly related to increased adiponectin and decreased IL-6 mRNA in PAT.     

血脂异常者血清MCP-1、HO-1、APN和TNF-α水平的检测及临床价值

目的探讨血脂异常者血清单核细胞趋化蛋白-l(MCP-1)、血红素加氧酶-1(HO-1)、脂联素(APN)及肿瘤坏死因子α(TNF-α)水平的检测及临床价值。方法采用酶联免疫吸附法(ELISA)检测85例血脂异常者和35例健康对照者血清MCP-1、HO-1、APN及TNF-α的水平,同时检测血脂异常者血清其他脂类代谢指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)]的水平,并分析MCP-1、HO-1、APN及TNF-α与脂类代谢指标的相关性。结果血脂异常者血清MCP-1、HO-1和APN水平较健康对照组均显著升高,差异具有统计学意义(P0.01),而TNF-α水平较健康对照组则明显降低,差异具有统计学意义(P0.01);同时血脂异常者血清HO-1水平与MCP-1及LDL-C水平均呈正相关关系;APN水平则与TNF-α呈负相关关系,与LDL-C水平呈正相关关系;而健康对照组的HO-1水平与MCP-1水平无明显关系。结论血脂异常者血清MCP-1、HO-1和APN水平显著升高,而TNF-α水平则明显降低,说明MCP-1、HO-1、APN及TNF-α可能参与了动脉粥样硬化的发生及发展,并可能成为动脉粥样硬化潜在的预防或治疗靶点。     

辛伐他汀对急性脑卒中患者血清脂联素和不对称性二甲基精氨酸水平的影响

目的 探讨辛伐他汀对急性脑卒中患者血清脂联素和不对称性二甲基精氨酸(ADMA)水平的影响.方法 选择急性脑卒中患者90例,按随机数字表法分为常规治疗组和干预治疗组,每组45例.计算两组患者脑梗死体积和临床神经功能缺损程度评分.酶联免疫吸附试验法检测两组治疗前后血清脂联素和ADMA水平.比较两组治疗前后脂联素和ADMA水平的变化,并分析其与脑梗死体积和临床神经功能缺损程度评分的相关性.结果 治疗前两组患者脂联素和ADMA水平比较差异无统计学意义(P＞0.05)；治疗后两组患者脂联素水平明显升高,ADMA水平明显下降,与治疗前比较差异有统计学意义(P＜0.05).但是干预治疗组治疗后脂联素水平明显高于同期常规治疗组,ADMA水平明显低于同期常规治疗组,差异有统计学意义[(5.92±0.15)mg/L比(4.51±0.13)mg/L,(0.96±0.13)μmol/L比(1.08±0.15)μ mol/L] (P＜ 0.05).等级相关分析结果显示患者治疗前脂联素水平与脑梗死体积和临床神经功能缺损程度评分均呈负相关,相关系数分别为-0.75和-0.59,P值均＜0.05.患者治疗前ADMA水平与脑梗死体积和临床神经功能缺损程度评分均呈正相关,相关系数分别为0.68和0.71,P值均＜0.05.结论 辛伐他汀能有效地升高急性脑卒中患者脂联素水平和降低ADMA水平,改善患者预后.