1-Linoleoylglycerophosphocholine stimulates UCP1-dependent thermogenesis and mitochondrial respiration to combat obesity.

IF 4.1 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rui Wang, Tianfu Zhu, Jingxian Lu, Mengke Cheng, Xingyun Wang, Xirong Guo, Shan Huang, Jianfang Gao
{"title":"1-Linoleoylglycerophosphocholine stimulates UCP1-dependent thermogenesis and mitochondrial respiration to combat obesity.","authors":"Rui Wang, Tianfu Zhu, Jingxian Lu, Mengke Cheng, Xingyun Wang, Xirong Guo, Shan Huang, Jianfang Gao","doi":"10.1016/j.jlr.2025.100914","DOIUrl":null,"url":null,"abstract":"<p><p>Obesity leads to numerous illnesses and metabolic disorders, with lysophosphatidylcholine (LPC) levels declining in obese patients. However, the physiological role of LPC and the regulatory mechanisms involved in modulating obesity remain largely unknown. Here, we provide evidence that 1-linoleoylglycerophosphocholine (1-LGPC) promotes adipocyte energy expenditure by activating the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (KEAP1-NRF2) axis. Metabolomic analyses identified 1-LGPC as a characteristic metabolite that declined in the peripheral blood of obese patients. Treatment with 1-LGPC effectively alleviated high-fat diet-induced lipid accumulation in zebrafish larvae and human adipocytes. Elevated expression levels, increased oxygen consumption rates, and enhanced transcript levels indicated that uncoupling protein 1-dependent thermogenesis and mitochondrial respiration were significantly boosted. Furthermore, NRF2 expression and nuclear translocation were induced by 1-LGPC, and NRF2 inhibition triggered UCP1 downregulation and lipid accumulation restoration, confirming the KEAP1-NRF2 axis's involvement in 1-LGPC-induced energy expenditure. These findings offer preliminary insights into physiological roles and mechanisms by which 1-LGPC modulates lipid and energy metabolism, providing potential strategies for obesity intervention using clinically identified compounds.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100914"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Lipid Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jlr.2025.100914","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Obesity leads to numerous illnesses and metabolic disorders, with lysophosphatidylcholine (LPC) levels declining in obese patients. However, the physiological role of LPC and the regulatory mechanisms involved in modulating obesity remain largely unknown. Here, we provide evidence that 1-linoleoylglycerophosphocholine (1-LGPC) promotes adipocyte energy expenditure by activating the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (KEAP1-NRF2) axis. Metabolomic analyses identified 1-LGPC as a characteristic metabolite that declined in the peripheral blood of obese patients. Treatment with 1-LGPC effectively alleviated high-fat diet-induced lipid accumulation in zebrafish larvae and human adipocytes. Elevated expression levels, increased oxygen consumption rates, and enhanced transcript levels indicated that uncoupling protein 1-dependent thermogenesis and mitochondrial respiration were significantly boosted. Furthermore, NRF2 expression and nuclear translocation were induced by 1-LGPC, and NRF2 inhibition triggered UCP1 downregulation and lipid accumulation restoration, confirming the KEAP1-NRF2 axis's involvement in 1-LGPC-induced energy expenditure. These findings offer preliminary insights into physiological roles and mechanisms by which 1-LGPC modulates lipid and energy metabolism, providing potential strategies for obesity intervention using clinically identified compounds.

1-亚油酰甘油磷脂胆碱刺激ucp1依赖的产热和线粒体呼吸来对抗肥胖。
肥胖会导致许多疾病和代谢紊乱,肥胖患者的溶血磷脂酰胆碱(LPC)水平下降。然而,LPC的生理作用和调节肥胖的调节机制在很大程度上仍然未知。在这里,我们提供的证据表明,1-亚油基甘油磷脂胆碱(1-LGPC)通过激活kelch样ech相关蛋白1-核因子2-相关因子2 (KEAP1-NRF2)轴促进脂肪细胞的能量消耗。代谢组学分析确定1-LGPC是肥胖患者外周血中下降的特征性代谢物。用1-LGPC处理可有效缓解高脂肪饮食诱导的斑马鱼幼虫和人类脂肪细胞的脂质积累。表达水平升高、耗氧量增加和转录物水平增强表明,解偶联蛋白1依赖性产热作用和线粒体呼吸作用显著增强。此外,NRF2表达和核易位被1-LGPC诱导,NRF2抑制引发UCP1下调和脂质积累恢复,证实了KEAP1-NRF2轴参与1-LGPC诱导的能量消耗。这些发现为1-LGPC调节脂质和能量代谢的生理作用和机制提供了初步的见解,为使用临床鉴定的化合物干预肥胖提供了潜在的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信