Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.

IF 14.3 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yucheng Zhu, Ruiqi Yang, Zhangchao Deng, Bohua Deng, Kun Zhao, Chen Dai, Gang Wei, YanJiang Wang, Jinshui Zheng, Zhuqing Ren, Wentao Lv, Yingping Xiao, Zhinan Mei, Tongxing Song
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Abstract

Obesity represents a low-grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low-dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue-resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15-HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12-LOX) and 15- Hydroxyeicosatetraenoic acid (15-HETE) rescues the impaired thermogenesis. Interestingly, 15-HETE directly binds to AMP-activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15-HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity.

脂肪组织栖息的Sphingomonas Paucimobilis通过减少15-HETE的产生和抑制AMPK途径抑制适应性产热
肥胖是一种低度慢性炎症状态,与适应性产热功能受损有关。然而,慢性炎症激活产热缺陷的机制仍不清楚。本文首先通过在小鼠冷暴露前注射低剂量脂多糖(LPS)建立了一个慢性炎症模型,然后验证了LPS处理能降低小鼠的核心体温并改变附睾白色脂肪组织(eWAT)中微生物的分布。研究发现,一种驻留在脂肪组织的细菌 Sphingomonas paucimobilis 可能会抑制棕色脂肪的激活和腹股沟脂肪组织的棕色化,从而导致适应性产热缺陷。LPS 和 S. paucimobilis 通过抑制 15-HETE 的主要代谢酶 12 脂氧合酶(12-LOX),从机制上抑制了 15-HETE 的产生和释放,而 15- 羟基二十碳四烯酸(15-HETE)则能挽救受损的产热。有趣的是,15-HETE 可直接与 AMP 激活蛋白激酶 α(AMPKα)结合,提高 AMPK 的磷酸化程度,从而激活解偶联蛋白 1(UCP1)和线粒体氧化磷酸化(OXPHOS)复合物。对人类肥胖症受试者的进一步分析表明,体重指数高的个体显示出较低的 15-HETE 水平。综上所述,这项研究加深了人们对慢性炎症如何损害适应性产热的理解,并为缓解肥胖症提供了新的靶点。
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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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