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Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue of male mice

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Listed:
  • Xiaoxue Jiang

    (Fudan University)

  • Kan liu

    (Chinese Academy of Sciences)

  • Peixiang Luo

    (Chinese Academy of Sciences)

  • Zi Li

    (Chinese Academy of Sciences)

  • Fei Xiao

    (Fudan University)

  • Haizhou Jiang

    (Fudan University)

  • Shangming Wu

    (Chinese Academy of Sciences)

  • Min Tang

    (Fudan University)

  • Feixiang Yuan

    (Fudan University)

  • Xiaoying Li

    (Fudan University)

  • Yousheng Shu

    (Fudan University)

  • Bo Peng

    (Fudan University)

  • Shanghai Chen

    (Fudan University)

  • Shihong Ni

    (Fudan University)

  • Feifan Guo

    (Fudan University)

Abstract

The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.

Suggested Citation

  • Xiaoxue Jiang & Kan liu & Peixiang Luo & Zi Li & Fei Xiao & Haizhou Jiang & Shangming Wu & Min Tang & Feixiang Yuan & Xiaoying Li & Yousheng Shu & Bo Peng & Shanghai Chen & Shihong Ni & Feifan Guo, 2024. "Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue of male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52059-1
    DOI: 10.1038/s41467-024-52059-1
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    References listed on IDEAS

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    1. Xinyang Song & Ximei Sun & Sungwhan F. Oh & Meng Wu & Yanbo Zhang & Wen Zheng & Naama Geva-Zatorsky & Ray Jupp & Diane Mathis & Christophe Benoist & Dennis L. Kasper, 2020. "Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis," Nature, Nature, vol. 577(7790), pages 410-415, January.
    2. Zi-Bing Jin & Xiu-Feng Huang & Ji-Neng Lv & Lue Xiang & Dong-Qing Li & Jiangfei Chen & Changjiang Huang & Jinyu Wu & Fan Lu & Jia Qu, 2014. "SLC7A14 linked to autosomal recessive retinitis pigmentosa," Nature Communications, Nature, vol. 5(1), pages 1-9, May.
    3. Fei Xiao & Haizhou Jiang & Zi Li & Xiaoxue Jiang & Shanghai Chen & Yuguo Niu & Hanrui Yin & Yousheng Shu & Bo Peng & Wei Lu & Xiaoying Li & Zhigang Li & Shujue Lan & Xiaoyan Xu & Feifan Guo, 2023. "Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
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