长期间歇性冷暴露干预脂肪组织代谢调控机体葡萄糖稳态

周鑫; 王澜; 张晨亮; 林树; 宋治远

doi:10.16016/j.1000-5404.201901189

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长期间歇性冷暴露干预脂肪组织代谢调控机体葡萄糖稳态

基础医学 | 更新时间：2026-01-09

- 长期间歇性冷暴露干预脂肪组织代谢调控机体葡萄糖稳态
- Long-term intermittent cold exposure regulates glucose homeostasis via intervening metabolism of adipose tissue in mice
- 第三军医大学学报 2019年41卷第11期页码：1044-1051
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院心血管内科，重庆市介入心脏病学研究所
- 作者简介：
  
  [宋治远，E-mail: zysong2010@126.conSONG Zhiyuan, E-mail:zysong2010@126.con
- 基金信息：
  
  国家自然科学基金面上项目(81570395)
- DOI：10.16016/j.1000-5404.201901189
  中图分类号： Q591.4;Q591.5;R339.55
- 收稿：2019-01-23，
  
  修回：2019-04-17，
  
  纸质出版：2019-06-15
- 稿件说明：
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周鑫, 王澜, 张晨亮, 等. 长期间歇性冷暴露干预脂肪组织代谢调控机体葡萄糖稳态[J]. 第三军医大学学报, 2019,41(11):1044-1051.

Xin ZHOU, Lan WANG, Chenliang ZHANG, et al. Long-term intermittent cold exposure regulates glucose homeostasis via intervening metabolism of adipose tissue in mice[J]. Journal of Third Military Medical University, 2019, 41(11): 1044-1051.
周鑫, 王澜, 张晨亮, 等. 长期间歇性冷暴露干预脂肪组织代谢调控机体葡萄糖稳态[J]. 第三军医大学学报, 2019,41(11):1044-1051. DOI： 10.16016/j.1000-5404.201901189.

Xin ZHOU, Lan WANG, Chenliang ZHANG, et al. Long-term intermittent cold exposure regulates glucose homeostasis via intervening metabolism of adipose tissue in mice[J]. Journal of Third Military Medical University, 2019, 41(11): 1044-1051. DOI： 10.16016/j.1000-5404.201901189.

摘要

目的

通过对小鼠进行长期间歇性冷暴露，探讨冷暴露对机体葡萄糖稳态的改善作用以及对高脂饮食诱导葡萄糖稳态损害的预防作用，并分析脂肪组织在该过程中所起的调控作用。

方法

取24只8周龄雄性C57BL/6J小鼠均分成4组，分别为对照组(正常普通饲料+常温)、冷暴露组(正常普通饲料+4 ℃，2 h/d)、高脂对照组(高脂饲料+常温)、高脂+冷暴露组(高脂饲料+4 ℃，2 h/d)。在分组后1、8、16、22周时分别进行葡萄糖耐量和胰岛素耐量实验，22周后取小鼠肩胛处棕色脂肪和腹股沟皮下脂肪进行转录组测序。

结果

22周间歇性冷暴露在不影响小鼠体质量的前提下，可以显著降低体内皮下脂肪的质量[对照组(0.338±0.024)g

冷暴露组(0.221±0.016)g

0.05

]

，显著提升棕色脂肪的质量[对照组(0.079±0.003)g

冷暴露组(0.095±0.005)g

0.05

]

，并使糖耐量水平提高25.9%(

0.01)，胰岛素敏感性提升50.4%(

0.01)，葡萄糖稳态改善的程度和冷暴露的时间呈正相关。在高脂饮食条件下，22周间歇性冷暴露显著抑制了其引发的体质量增加[高脂对照组(43.3±1.8)g

高脂+冷暴露组(32.9±0.7)g

0.01

]

和皮下脂肪质量增加[高脂对照组(1.186±0.215)g

高脂+冷暴露组(0.434±0.059)g

0.05

]

，并使糖耐量不足改善了25.5%(

0.01)，胰岛素抵抗改善了33.9%(

0.01)。转录组测序分析表明长期间歇性冷暴露显著激活棕色脂肪和白色脂肪的葡萄糖代谢、PI3K-Akt和胰

岛素信号通路(

0.05)，但在高脂饮食条件下冷暴露对白色脂肪组织葡萄糖代谢相关通路的激活作用不明显。

结论

长期间歇性冷暴露可以显著改善小鼠葡萄糖稳态，并可以预防高脂饮食对葡萄糖稳态的损害，其可能是通过激活脂肪组织葡萄糖代谢、PI3K-Akt和胰岛素信号通路来发挥作用。

Abstract

Objective

By stimulating intermittent cold exposure to mice for a long term

to investigate the effect of cold exposure on amelioration of glucose homeostasis and prevention of glucose homeostasis disorder induced by high-fat diet (HFD)

and analyze the regulative effect of adipose tissue in the process.

Methods

A total of 24 male C57 BL/6J male mice (8 weeks old) were equally divided into 4 groups

that is

control group (normal diet+room temperature)

cold exposure group (normal diet+4 ℃

2 h/d)

HFD group (HFD feeding+room temperature)

and HFD and cold exposure group. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were carried out in 1

16 and 22 weeks after intervention. In 22 weeks after intervention

scapular brown adipose tissue (BAT) and inguinal white adipose tissue (WATi) were collected for transcriptome profiling analysis.

Results

When having no effect on the bodyweight

intermittent cold exposure for 22 weeks significantly reduced the weight of WATi (0.221±0.016

0.338±0.024 g

0.05)

but increased the weight of BAT (0.095±0.005

0.079±0.003 g

0.05) when compared with the control group

and elevated glucose tolerance by 25.9% (

0.01) and enhanced insulin sensitivity by 50.4% (

0.01). The amelioration of glucose homeostasis was positively correlated with the length of cold exposure. However

in the mice with HFD feeding

the cold exposure inhibited the increase of bodyweight (43.3±1.8

32.9±0.7 g

0.01) and WATi (1.186±0.215

0.434±0.059 g

0.05)

and improved insufficient glucose tolerance by 25.5% (

0.01) and insulin resistance by 33.9% (

0.01) when compared to the mice of HFD and cold exposure group. Transcriptome profiling analysis showed that long-term intermittent cold exposure obviously activated the glycolysis in the brown fat and white fat tissues

and the PI3K-Akt and insulin signaling pathways (

0.01)

but HFD reversed the activation of glycolysis-related pathways in white fat tissues.

Conclusion

Long-term intermittent cold exposure may promote glucose homeostasis and prevent glucose homeostasis disorder induced by HFD

via

activating glycolysis

PI3K-Akt and insulin signaling pathways in adipose tissue.

关键词

Keywords

references

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