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SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling

Author

Listed:
  • Hongrui Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Liang Yu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jin’e Wang

    (China Three Gorges University)

  • Yaqing Zhang

    (China Three Gorges University)

  • Mengchen Xu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Cheng Lv

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Bing Cui

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Mengmeng Yuan

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yu Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yupeng Yan

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Rutai Hui

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yibo Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

White adipose tissue browning can promote lipid burning to increase energy expenditure and improve adiposity. Here, we show that Slc35d3 expression is significantly lower in adipose tissues of obese mice. While adipocyte-specific Slc35d3 knockin is protected against diet-induced obesity, adipocyte-specific Slc35d3 knockout inhibits white adipose tissue browning and causes decreased energy expenditure and impaired insulin sensitivity in mice. Mechanistically, we confirm that SLC35D3 interacts with the NOTCH1 extracellular domain, which leads to the accumulation of NOTCH1 in the endoplasmic reticulum and thus inhibits the NOTCH1 signaling pathway. In addition, knockdown of Notch1 in mouse inguinal white adipose tissue mediated by orthotopic injection of AAV8-adiponectin-shNotch1 shows considerable improvement in obesity and glucolipid metabolism, which is more pronounced in adipocyte-specific Slc35d3 knockout mice than in knockin mice. Overall, in this study, we reveal that SLC35D3 is involved in obesity via NOTCH1 signaling, and low adipose SLC35D3 expression in obesity might be a therapeutic target for obesity and associated metabolic disorders.

Suggested Citation

  • Hongrui Wang & Liang Yu & Jin’e Wang & Yaqing Zhang & Mengchen Xu & Cheng Lv & Bing Cui & Mengmeng Yuan & Yu Zhang & Yupeng Yan & Rutai Hui & Yibo Wang, 2023. "SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43418-5
    DOI: 10.1038/s41467-023-43418-5
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    References listed on IDEAS

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    2. Jingyuan Li & Li Gong & Shaozhuang Liu & Yujie Zhang & Chunmei Zhang & Mi Tian & Huixia Lu & Peili Bu & Jianmin Yang & Changhan Ouyang & Xiuxin Jiang & Jiliang Wu & Yun Zhang & Qing Min & Cheng Zhang , 2019. "Adipose HuR protects against diet-induced obesity and insulin resistance," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Fabrizio C. Lucchini & Stephan Wueest & Tenagne D. Challa & Flurin Item & Salvatore Modica & Marcela Borsigova & Yulia Haim & Christian Wolfrum & Assaf Rudich & Daniel Konrad, 2020. "ASK1 inhibits browning of white adipose tissue in obesity," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    4. Eric H. Schroeter & Jeffrey A. Kisslinger & Raphael Kopan, 1998. "Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain," Nature, Nature, vol. 393(6683), pages 382-386, May.
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    Cited by:

    1. Ting Zeng & Liuling Xiao & Jiajie Li & Han Wu & Xiaolong Guo & Fukang Zhu & Xinyu Yu & Yewei Cui & Xueya Zhao & Yumeng Wang & Ting Zhang & Weijiong He & Hongxiang Zeng & Xi Li, 2025. "Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    2. Xuetao Ji & Xu Zhang & Tong Zhang & Yao Xue & Mengping He & Chaopu Li & Yun Huang & Haoyu Wang & Jing Ju & Li’e Cai & Yuzhu Wang & Ning Wang & Lijuan Fan & Hui Tong & Heng Fan & Qinsheng Chen & Qinwei, 2025. "PNPLA7 mediates Parkin-mitochondrial recruitment in adipose tissue for mitophagy and inhibits browning," Nature Communications, Nature, vol. 16(1), pages 1-20, December.

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