微生物群-肠道-脂肪轴：丁酸盐介导的对炎症反应的改善作用以及对脂肪酸氧化失调的调节减轻了睡眠受限小鼠的肥胖。

Microbiota-gut-adipose axis: butyrate-mediated the improvement effect on inflammatory response and fatty acid oxidation dysregulation attenuates obesity in sleep-restricted mice.

作者信息

Gao Ting, Feng Minghui, Wang Zixu, Cao Jing, Chen Yaoxing

机构信息

National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China; Department of Nutrition and Health, China Agricultural University, Haidian, Beijing 100193, China.

National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China.

出版信息

Microbes Infect. 2023 Jul-Aug;25(6):105125. doi: 10.1016/j.micinf.2023.105125. Epub 2023 Mar 10.

DOI:10.1016/j.micinf.2023.105125

PMID:36906253

Abstract

BACKGROUND

Insufficient sleep was considered as a substantial cause of obesity. The present study further explored the mechanism whereby sleep restriction (SR)-mediated intestinal dysbiosis induced metabolic disorder and ultimately lead to obesity in mice and the improvement effect of butyrate exerting on it.

METHODS

A continuous 3 months SR mouse model with or without butyrate supplementation and fecal microbiota transplantation to explore the key role of intestinal microbiota in butyrate improving inflammatory response in inguinal white adipose tissue (iWAT) and fatty acid oxidation dysfunction in brown adipose tissue (BAT), further ameliorating SR-induced obesity.

RESULTS

SR-mediated gut microbiota dysbiosis (down-regulation in butyrate level and up-regulation in LPS level) induced intestinal permeability increase and inflammatory response in iWAT and fatty acid oxidation dysfunction in BAT, ultimately resulting in obesity. Further, we demonstrated butyrate ameliorated gut microbiota homeostasis, suppressed inflammatory response via GPR43/LPS/TLR4/MyD88/GSK-3β/β-catenin loop in iWAT and restored fatty acid oxidation function via HDAC3/PPARα/PGC-1α/UCP1/Calpain1 pathway in BAT, ultimately reversing SR-induced obesity.

CONCLUSIONS

We revealed that gut dysbiosis is a key factor for SR-induced obesity and provided a better understanding of the effects of butyrate. We further expected that reversing SR-induced obesity by improving microbiota-gut-adipose axis disorder could be a possible treatment for metabolic diseases.

摘要

背景

睡眠不足被认为是肥胖的一个重要原因。本研究进一步探讨了睡眠限制（SR）介导的肠道菌群失调诱导代谢紊乱并最终导致小鼠肥胖的机制，以及丁酸盐对其的改善作用。

方法

建立连续3个月的SR小鼠模型，补充或不补充丁酸盐，并进行粪便微生物群移植，以探讨肠道微生物群在丁酸盐改善腹股沟白色脂肪组织（iWAT）炎症反应和棕色脂肪组织（BAT）脂肪酸氧化功能障碍中的关键作用，进一步改善SR诱导的肥胖。

结果

SR介导的肠道微生物群失调（丁酸盐水平下调和LPS水平上调）导致肠道通透性增加、iWAT炎症反应以及BAT脂肪酸氧化功能障碍，最终导致肥胖。此外，我们证明丁酸盐改善了肠道微生物群稳态，通过GPR43/LPS/TLR4/MyD88/GSK-3β/β-连环蛋白环抑制iWAT中的炎症反应，并通过HDAC3/PPARα/PGC-1α/UCP1/钙蛋白酶1途径恢复BAT中的脂肪酸氧化功能，最终逆转SR诱导的肥胖。