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LncRNA LINK-A Remodels Tissue Inflammatory Microenvironments to Promote Obesity.

Yu Chen | Hui Chen | Ying Wang | Fangzhou Liu | Xiao Fan | Chengyu Shi | Xinwan Su | Manman Tan | Yebin Yang | Bangxing Lin | Kai Lei | Lei Qu | Jiecheng Yang | Zhipeng Zhu | Zengzhuang Yuan | Shanshan Xie | Qinming Sun | Dante Neculai | Wei Liu | Qingfeng Yan | Xiang Wang | Jianzhong Shao | Jian Liu | Aifu Lin
Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 2024

High-fat diet (HFD)-induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity-associated human lncRNA LINK-A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD-induced obesity knock-in (KI) mouse model. Mechanistically, HFD LINK-A KI mice induce the infiltration of inflammatory factors, including IL-1β and CXCL16, through the LINK-A/HB-EGF/HIF1α feedback loop axis in a self-amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK-A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK-A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD-induced obesity and metabolic syndrome, pointing out LINK-A as a valuable and effective therapeutic target for treating HFD-induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK-A) in remodeling tissue inflammatory microenvironments to promote HFD-induced obesity.

Pubmed ID: 38145352

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Associated grants

  • Agency: National Natural Science Fund for Distinguished Young Scholars,
    Id: 32225014
  • Agency: National Natural Science Foundation of China,
    Id: 81672791
  • Agency: National Natural Science Foundation of China,
    Id: 81872300
  • Agency: National Natural Science Foundation of China,
    Id: 82172899
  • Agency: National Key R&D Program of China,
    Id: 2021YFC2700903
  • Agency: "Lingyan" R&D Research and Development Project,
    Id: 2023C03023
  • Agency: Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China,
    Id: LR18C060002
  • Agency: Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China,
    Id: LR22H160002
  • Agency: Fundamental Research Funds for the Central Universities,
    Id: K20220228

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RRID:SCR_016718

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