Gao Ting, Feng Minghui, Wang Zixu, Cao Jing, Chen Yaoxing
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.
Microbes Infect. 2023 Jul-Aug;25(6):105125. doi: 10.1016/j.micinf.2023.105125. Epub 2023 Mar 10.
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.
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.
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.
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.
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。
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。
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。
我们揭示肠道菌群失调是SR诱导肥胖的关键因素，并更好地理解了丁酸盐的作用。我们进一步期望通过改善微生物群-肠道-脂肪轴紊乱来逆转SR诱导的肥胖可能是治疗代谢性疾病的一种方法。
