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短期高血糖对肥胖女性饮食诱导体重减轻多阶段过程中体内选定细胞因子在脂肪组织中的通量的影响。

Effect of short-term hyperglycemia on adipose tissue fluxes of selected cytokines in vivo during multiple phases of diet-induced weight loss in obese women.

作者信息

Siklova Michaela, Simonsen Lene, Polak Jan, Stich Vladimir, Bülow Jens

机构信息

Department of Sports Medicine (M.S., J.P., V.S.), Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic; Department of Clinical Physiology (L.S., J.B.), Bispebjerg University Hospital, 2400 Copenhagen, Denmark; and Department of Biomedical Sciences (J.B.), University of Copenhagen, DK-1165 Copenhagen, Denmark.

出版信息

J Clin Endocrinol Metab. 2015 May;100(5):1949-56. doi: 10.1210/jc.2014-3846. Epub 2015 Mar 9.

Abstract

CONTEXT

Hyperglycemia is suggested to be one of the drivers of the proinflammatory state observed in obese and diabetic patients.

OBJECTIVES

The objectives of the study was to investigate whether sc abdominal adipose tissue (scAT) could be one of the important sources of proinflammatory cytokines released in response to short-term hyperglycemia and whether this secretion capacity could be influenced by weight loss.

DESIGN, PATIENTS, AND INTERVENTIONS: Output of cytokines and proteins of acute phase from scAT in response to a 3-hours hyperglycemic clamp was evaluated in nine obese women in vivo using Fick's principle. Moreover, the output of cytokines was analyzed during a multiphase dietary intervention consisting of 1 month on a very low-calorie diet and subsequent 5-month weight-stabilization phase.

MAIN OUTCOME MEASURE(S): The levels of cytokines and proteins of acute phase [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra), TNF-α, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A, and C-reactive protein] in arterial and venous plasma were measured during each dietary phase. The insulin sensitivity of scAT in respect to the antilipolytic effect of insulin during the clamp was assessed.

RESULTS

Hyperglycemia increased the output of cytokines IL-6, MCP-1, and IL-1Ra from scAT. This effect had a tendency to be reduced after weight loss. The output of other proinflammatory substances from scAT into circulation was not detected. The diet-induced weight loss was associated with the improvement of antilipolytic insulin sensitivity in scAT.

CONCLUSIONS

The results suggest that short-term hyperglycemia induces an increase of the output of cytokines IL-6, IL-1Ra, and MCP-1 from adipose tissue, and this deleterious hyperglycemia effect may be attenuated by the diet-induced weight reduction. This lowered responsiveness of the inflammation-related system may be an important feature of the weight reduction-induced improvement of the metabolic status of obese prediabetic individuals.

摘要

背景

高血糖被认为是肥胖和糖尿病患者中观察到的促炎状态的驱动因素之一。

目的

本研究的目的是调查皮下腹部脂肪组织(scAT)是否可能是短期高血糖反应中释放的促炎细胞因子的重要来源之一,以及这种分泌能力是否会受到体重减轻的影响。

设计、患者和干预措施:使用菲克原理在体内评估了9名肥胖女性皮下腹部脂肪组织对3小时高血糖钳夹的细胞因子和急性期蛋白输出。此外,在一个多阶段饮食干预过程中分析了细胞因子的输出,该干预包括1个月的极低热量饮食和随后5个月的体重稳定阶段。

主要观察指标

在每个饮食阶段测量动脉和静脉血浆中急性期细胞因子和蛋白[白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-1受体拮抗剂(IL-1Ra)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)、血清淀粉样蛋白A和C反应蛋白]的水平。评估了钳夹期间皮下腹部脂肪组织对胰岛素抗脂解作用的胰岛素敏感性。

结果

高血糖增加了皮下腹部脂肪组织中细胞因子IL-6、MCP-1和IL-1Ra的输出。体重减轻后这种作用有降低的趋势。未检测到皮下腹部脂肪组织中其他促炎物质进入循环的输出。饮食诱导的体重减轻与皮下腹部脂肪组织抗脂解胰岛素敏感性的改善有关。

结论

结果表明,短期高血糖会导致脂肪组织中细胞因子IL-6、IL-1Ra和MCP-1的输出增加,而饮食诱导的体重减轻可能会减弱这种有害的高血糖效应。炎症相关系统这种降低的反应性可能是体重减轻诱导肥胖糖尿病前期个体代谢状态改善的一个重要特征。

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