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Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis

Author

Listed:
  • Yi Zhu

    (The University of Texas Southwestern Medical Center at Dallas
    Baylor College of Medicine)

  • Na Li

    (The University of Texas Southwestern Medical Center at Dallas
    Tianjin Medical University General Hospital)

  • Mingyang Huang

    (Baylor College of Medicine)

  • Mason Bartels

    (The University of Texas Southwestern Medical Center at Dallas)

  • Sophie Dogné

    (University of Namur)

  • Shangang Zhao

    (The University of Texas Southwestern Medical Center at Dallas)

  • Xi Chen

    (Baylor College of Medicine)

  • Clair Crewe

    (The University of Texas Southwestern Medical Center at Dallas)

  • Leon Straub

    (The University of Texas Southwestern Medical Center at Dallas)

  • Lavanya Vishvanath

    (The University of Texas Southwestern Medical Center at Dallas)

  • Zhuzhen Zhang

    (The University of Texas Southwestern Medical Center at Dallas)

  • Mengle Shao

    (The University of Texas Southwestern Medical Center at Dallas)

  • Yongjie Yang

    (Baylor College of Medicine)

  • Christy M. Gliniak

    (The University of Texas Southwestern Medical Center at Dallas)

  • Ruth Gordillo

    (The University of Texas Southwestern Medical Center at Dallas)

  • Gordon I. Smith

    (Washington University School of Medicine in St. Louis.)

  • William L. Holland

    (The University of Texas Southwestern Medical Center at Dallas
    University of Utah College of Health)

  • Rana K. Gupta

    (The University of Texas Southwestern Medical Center at Dallas)

  • Bingning Dong

    (Baylor College of Medicine)

  • Nathalie Caron

    (University of Namur)

  • Yong Xu

    (Baylor College of Medicine)

  • Yucel Akgul

    (The University of Texas Southwestern Medical Center at Dallas)

  • Samuel Klein

    (Washington University School of Medicine in St. Louis.)

  • Philipp E. Scherer

    (The University of Texas Southwestern Medical Center at Dallas
    The University of Texas Southwestern Medical Center at Dallas)

Abstract

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma HA. Instead, an HA-driven systemic substrate redistribution and adipose tissue-liver crosstalk contributes to the systemic glucose improvements. In summary, we demonstrate an unexpected improvement in glucose metabolism as a consequence of HA overproduction in adipose tissue, which argues against the use of systemic HA synthesis inhibitors to treat obesity and T2D.

Suggested Citation

  • Yi Zhu & Na Li & Mingyang Huang & Mason Bartels & Sophie Dogné & Shangang Zhao & Xi Chen & Clair Crewe & Leon Straub & Lavanya Vishvanath & Zhuzhen Zhang & Mengle Shao & Yongjie Yang & Christy M. Glin, 2021. "Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25025-4
    DOI: 10.1038/s41467-021-25025-4
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