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Adipose tissue-derived PRXL2A suppresses hepatic lipogenesis in a study with male mice

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Listed:
  • Zhiyuan Li

    (Tsinghua University)

  • Zheng Tian

    (Tsinghua University)

  • Xiaoliu Shi

    (Tsinghua University)

  • Aijun Long

    (Tsinghua University)

  • Yazhuo Wang

    (Tsinghua University)

  • Yan Yang

    (The Second Xiangya Hospital of Central South University)

  • Yaqi Wang

    (The Second Xiangya Hospital of Central South University)

  • Jingjing Zhang

    (The Second Xiangya Hospital of Central South University)

  • Yiguo Wang

    (Tsinghua University)

Abstract

Hepatic de novo lipogenesis (DNL) is crucial for maintaining lipid homeostasis, and its dysregulation is implicated in various metabolic diseases. While it is well established that hepatic DNL is tightly regulated by hormones such as insulin and glucagon secreted from the pancreatic islets during feeding and fasting, further investigations are required to identify more hormones affecting hepatic DNL during the feeding-fasting transition. Here, we identify PRXL2A (peroxiredoxin like 2 A), an adipokine secreted during fasting, as an inhibitor of hepatic DNL. Mechanistically, PRXL2A binds to its receptor PTAFR (platelet activating factor receptor), promoting calcium mobilization and activating AMPK (AMP-activated protein kinase), thereby suppressing SREBP1 (sterol regulatory element-binding protein 1)-controlled hepatic DNL. Disruption of this axis by knockout of either Prxl2a or Ptafr increases hepatic DNL and lipid accumulation. Exogenous PRXL2A reduces hepatic DNL, suggesting a potential therapeutic strategy for diseases associated with hepatic lipid accumulation. Therefore, the PRXL2A-PTAFR signaling axis links adipose tissues and the liver to regulate hepatic lipid metabolism.

Suggested Citation

  • Zhiyuan Li & Zheng Tian & Xiaoliu Shi & Aijun Long & Yazhuo Wang & Yan Yang & Yaqi Wang & Jingjing Zhang & Yiguo Wang, 2025. "Adipose tissue-derived PRXL2A suppresses hepatic lipogenesis in a study with male mice," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61963-z
    DOI: 10.1038/s41467-025-61963-z
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    References listed on IDEAS

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    1. Alan R. Saltiel & C. Ronald Kahn, 2001. "Insulin signalling and the regulation of glucose and lipid metabolism," Nature, Nature, vol. 414(6865), pages 799-806, December.
    2. Jinbo Han & Erwei Li & Liqun Chen & Yuanyuan Zhang & Fangchao Wei & Jieyuan Liu & Haiteng Deng & Yiguo Wang, 2015. "The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1," Nature, Nature, vol. 524(7564), pages 243-246, August.
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