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Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling

Author

Listed:
  • Dongliang Lu

    (Washington University School of Medicine)

  • Anyuan He

    (Washington University School of Medicine
    Anhui Medical University)

  • Min Tan

    (Washington University School of Medicine)

  • Marguerite Mrad

    (Washington University School of Medicine)

  • Amal El Daibani

    (Washington University School of Medicine)

  • Donghua Hu

    (Washington University School of Medicine)

  • Xuejing Liu

    (Washington University School of Medicine)

  • Brian Kleiboeker

    (Washington University School of Medicine)

  • Tao Che

    (Washington University School of Medicine)

  • Fong-Fu Hsu

    (Washington University School of Medicine)

  • Monika Bambouskova

    (Washington University School of Medicine)

  • Clay F. Semenkovich

    (Washington University School of Medicine
    Department of Cell Biology and Physiology; Washington University School of Medicine)

  • Irfan J. Lodhi

    (Washington University School of Medicine)

Abstract

The liver gene expression of the peroxisomal β-oxidation enzyme acyl-coenzyme A oxidase 1 (ACOX1), which catabolizes very long chain fatty acids (VLCFA), increases in the context of obesity, but how this pathway impacts systemic energy metabolism remains unknown. Here, we show that hepatic ACOX1-mediated β-oxidation regulates inter-organ communication involved in metabolic homeostasis. Liver-specific knockout of Acox1 (Acox1-LKO) protects mice from diet-induced obesity, adipose tissue inflammation, and systemic insulin resistance. Serum from Acox1-LKO mice promotes browning in cultured white adipocytes. Global serum lipidomics show increased circulating levels of several species of ω−3 VLCFAs (C24-C28) with previously uncharacterized physiological role that promote browning, mitochondrial biogenesis and Glut4 translocation through activation of the lipid sensor GPR120 in adipocytes. This work identifies hepatic peroxisomal β-oxidation as an important regulator of metabolic homeostasis and suggests that manipulation of ACOX1 or its substrates may treat obesity-associated metabolic disorders.

Suggested Citation

  • Dongliang Lu & Anyuan He & Min Tan & Marguerite Mrad & Amal El Daibani & Donghua Hu & Xuejing Liu & Brian Kleiboeker & Tao Che & Fong-Fu Hsu & Monika Bambouskova & Clay F. Semenkovich & Irfan J. Lodhi, 2024. "Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48471-2
    DOI: 10.1038/s41467-024-48471-2
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    References listed on IDEAS

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