Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

Aims/hypothesis We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPAR co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance.Methods Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic–hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot.Results Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPAR co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor- increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects.Conclusions/interpretation Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.     

脂联素与动脉粥样硬化

脂联素是新近发现的脂肪细胞特异性蛋白,研究显示脂联素通过抑制内皮细胞黏附因子的表达、平滑肌细胞的增殖以及巨噬细胞向泡沫细胞的转变,终止炎症反应、改善脂代谢等几个方面与动脉粥样硬化密切相关,对其进一步研究将提高对动脉粥样硬化发生发展的认识,为动脉粥样硬化的防治提供一个新的思路。     

健脾祛湿方对2型糖尿病并非酒精性脂肪肝患者脂联素、肿瘤坏死因子-α和肝脏脂肪含量的影响

【目的】观察健脾祛湿方对2型糖尿病（type 2 diabetes mellitus, T2DM）并非酒精性脂肪肝（non-alcoholic fatty liver disease, NAFLD）患者脂联素（adiponectin, APN）、肿瘤坏死因子-α（tumor necrosis facto al’pha, TNF-α）及肝脏脂肪含量变化的影响。【方法】将120例T2DM并NAFLD患者随机分为健脾祛湿方组（治疗组）和吡格列酮组（对照组）各60例,在基础降糖治疗的同时,分别给予健脾祛湿方和吡格列酮治疗,观察时间均为24周。利用声触诊组织量化成像技术（virtual touch tissue quantification technique, VTQ）、酶联免疫吸附（ ELISA）法和生化分析仪观察2组治疗前后肝脏脂肪含量、 APN、TNF-α、血糖、血脂和肝功能等指标的变化。【结果】治疗后,2组空腹血糖（FPG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、 TNF-α含量及肝实质ARFI (acoustic radiation force impulse)值较治疗前均显著下降(P<0．05),高密度脂蛋白胆固醇（HDL-C）、 APN含量较治疗前显著上升(P<0．05);治疗组治疗前后FINS、 TNF-α差值大于对照组(P<0．05)。【结论】健脾祛湿方可能通过升高APN、降低TNF-α,从而达到纠正糖脂代谢紊乱,保护胰岛功能以及减少肝脏脂肪含量的功效。     

中药正肝汤对乙型肝炎肝硬化患者血清瘦素、脂联素水平以及胰岛素抵抗影响的分析

目的 观察中药制剂正肝汤治疗乙型肝炎(乙肝)肝硬化患者对其血清瘦素(LEP)、脂联素(ADP)水平及胰岛素抵抗(IR)的影响。方法 将入选的66例乙肝肝硬化患者随机分为对照组(31例)和治疗组(35例), 其中对照组选用肌苷片和维生素C口服治疗, 治疗组在此基础上, 应用正肝汤治疗, 疗程为3个月, 测定治疗前后患者血清LEP、ADP水平及IR指数。结果 对照组血清LEP、ADP水平和IR指数与治疗前比较, 差异无统计学意义(P>0.05);治疗组血清LEP、ADP水平和IR指数较治疗前明显下降, 差异有统计学意义(P<0.05), 治疗组血清LEP和ADP水平与对照组比较, 差异有统计学意义(P<0.05)。结论 正肝汤治疗乙肝肝硬化患者具有降低血清LEP、ADP水平, 并有改善IR的作用。     

A high-fat maternal diet decreases adiponectin receptor-1 expression in offspring

In early life, over-nutrition may increase the risk of insulin resistance in the adult stage. Adiponectin and its receptor may play a key role in this process. This study aimed to identify the effect of a high-fat (HF) maternal diet on metabolic parameters and muscle adiponectin signaling in young adult offspring. We found that offspring born to dams fed HF chow (HF; 31% of calories from fat) had elevated body and adipose tissue weight and higher serum glucose levels after glucose challenge at three weeks (W3) and eight weeks (W8) of age. Offspring exposed to a HF diet also had higher serum adiponectin levels at W3 compared to controls. However, adiponectin levels were significantly decreased compared to controls by W8. Adiponectin receptor 1?mRNA expression in skeletal muscle was decreased in the HF group at W3 and W8, and there was no difference between the two groups in adiponectin receptor 2 expression. Furthermore, glucose transporter 4?mRNA and protein expression was decreased in the skeletal muscle of the HF group at W3 and W8. Our results suggest that a HF maternal diet decreases adiponectin receptor 1 expression in the offspring, which could contribute to reduced sensitivity to adiponectin and to adverse nutritional programing outcomes.     

脂联素减轻心脏骤停后综合征小鼠脑损伤的机制研究

目的 在建立心脏骤停后综合征(PCAS)小鼠模型的基础上,探究脑组织神经细胞凋亡与炎症介质TNFα、IL-6的关系,以及经尾静脉注射脂联素(Adiponectin,APN)后,能否减少炎症介质释放,从而减轻神经细胞凋亡损伤。方法 将60只小鼠随机分为3组:心脏骤停后综合征组(PCAS组)、脂联素干预组(APN组)及对照组(C组)。使用经食道交流电诱发室颤导致心脏骤停,再经心肺复苏恢复自主循环的方式建立PCAS小鼠模型。APN组和PCAS组在自主循环恢复(ROSC)后,通过尾静脉分别注射10μg APN溶液0.25ml和等体积无菌生理盐水,分别在ROSC后第0.5、3、6、12h采集标本,采用TUNEL染色检测脑组织神经细胞凋亡情况; 免疫组化法半定量检测脑组织中TNFα、IL-6表达情况。结果 1PCAS组小鼠的脑组织出现噬神经、神经元细胞凋亡,脑组织内TNFα、IL-6表达增加。2PCAS后神经细胞凋亡数与TNF-α、IL-6之间具有正相关性(P<0.05)。3APN减少ROSC后脑组织的细胞凋亡,减轻脑组织内TNFα、IL-6的表达。结论 PCAS后小鼠脑组织中炎症因子TNFα、IL-6的释放导致脑组织神经细胞凋亡。APN可通过降低ROSC后小鼠脑组织中TNFα及IL-6的表达而减轻神经细胞凋亡。     

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.