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寒冷诱导的棕色脂肪组织活性改变男性血浆脂肪酸并改善葡萄糖代谢。

Cold-Induced Brown Adipose Tissue Activity Alters Plasma Fatty Acids and Improves Glucose Metabolism in Men.

作者信息

Iwen K Alexander, Backhaus Jenny, Cassens Melanie, Waltl Maren, Hedesan Oana C, Merkel Martin, Heeren Joerg, Sina Christian, Rademacher Leonie, Windjäger Anne, Haug Alexander R, Kiefer Florian W, Lehnert Hendrik, Schmid Sebastian M

机构信息

Department of Internal Medicine I, Section of Endocrinology & Diabetes, University Hospital Schleswig-Holstein, 23538 Lübeck, Germany.

Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria.

出版信息

J Clin Endocrinol Metab. 2017 Nov 1;102(11):4226-4234. doi: 10.1210/jc.2017-01250.

Abstract

CONTEXT

Mounting evidence suggests beneficial effects of brown adipose tissue (BAT) activation on glucose and lipid metabolism in humans. It is unclear whether cold-induced BAT activation affects not only insulin sensitivity but also insulin secretion. Likewise, the role in clearing circulating fatty acids (FAs) has not been fully explored.

OBJECTIVE

Exploring the effects of cold-induced BAT activation on insulin sensitivity and secretion, as well as on plasma FA profiles.

DESIGN

Fifteen healthy men participated in a cross-balanced repeated within-subject study with two experimental conditions. Subjects were exposed to thermoneutrality (22°C) and to moderate cold (18.06°C, shivering excluded) by use of a water-perfused whole body suit. Cold-induced BAT activation was quantified by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography in a subset of volunteers. A Botnia clamp procedure was applied to determine pancreatic first phase insulin response (FPIR) and insulin sensitivity. Hormones and metabolites, including 26 specific plasma FAs, were sampled throughout the experiment.

RESULTS

Cold exposure induced BAT activity. Plasma noradrenaline and dopamine concentrations increased in response to cold. Peripheral glucose uptake and insulin sensitivity significantly improved by ∼20%, whereas FPIR remained stable. Lignoceric acid (C24:0) concentrations increased, whereas levels of eicosanoic acid (C20:1n9), nervonic acid (C24:1n9), and behenic acid (C22:0) decreased.

CONCLUSIONS

Cold-exposure induces sympathetic nervous system activity and BAT metabolism in humans, resulting in improved glucose metabolism without affecting pancreatic insulin secretion. In addition, BAT activation is associated with altered circulating concentrations of distinct FAs. These data support the concept that human BAT metabolism significantly contributes to whole body glucose and lipid utilization in a coordinated manner.

摘要

背景

越来越多的证据表明,棕色脂肪组织(BAT)激活对人体的葡萄糖和脂质代谢具有有益作用。目前尚不清楚冷诱导的BAT激活是否不仅会影响胰岛素敏感性,还会影响胰岛素分泌。同样,其在清除循环脂肪酸(FAs)方面的作用尚未得到充分研究。

目的

探讨冷诱导的BAT激活对胰岛素敏感性和分泌以及血浆FA谱的影响。

设计

15名健康男性参与了一项交叉平衡的重复受试者内研究,该研究有两种实验条件。受试者通过使用水灌注全身套装,分别暴露于热中性环境(22°C)和中度寒冷环境(18.06°C,不包括颤抖)。在一部分志愿者中,通过[18F] - 氟脱氧葡萄糖正电子发射断层扫描 - 计算机断层扫描对冷诱导的BAT激活进行量化。采用博特尼亚钳夹法测定胰腺第一相胰岛素反应(FPIR)和胰岛素敏感性。在整个实验过程中采集激素和代谢物样本,包括26种特定的血浆FAs。

结果

冷暴露诱导了BAT活性。血浆去甲肾上腺素和多巴胺浓度因寒冷而升高。外周葡萄糖摄取和胰岛素敏感性显著提高了约20%,而FPIR保持稳定。二十四烷酸(C24:0)浓度升高,而二十碳烯酸(C20:1n9)、神经酸(C24:1n9)和山嵛酸(C22:0)水平降低。

结论

冷暴露可诱导人体交感神经系统活动和BAT代谢,从而改善葡萄糖代谢,而不影响胰腺胰岛素分泌。此外,BAT激活与不同FAs的循环浓度改变有关。这些数据支持了这样一种观点,即人体BAT代谢以协调的方式对全身葡萄糖和脂质利用做出了显著贡献。

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