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Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

Author

Listed:
  • Omer Keinan

    (University of California San Diego)

  • Joseph M. Valentine

    (University of California San Diego)

  • Haopeng Xiao

    (Dana–Farber Cancer Institute
    Harvard Medical School)

  • Sushil K. Mahata

    (VA San Diego Healthcare System and University of California San Diego)

  • Shannon M. Reilly

    (University of California San Diego)

  • Mohammad Abu-Odeh

    (University of California San Diego)

  • Julia H. Deluca

    (University of California San Diego)

  • Benyamin Dadpey

    (University of California San Diego)

  • Leslie Cho

    (University of California San Diego)

  • Austin Pan

    (University of California San Diego)

  • Ruth T. Yu

    (Salk Institute for Biological Sciences)

  • Yang Dai

    (Salk Institute for Biological Sciences)

  • Christopher Liddle

    (University of Sydney)

  • Michael Downes

    (Salk Institute for Biological Sciences)

  • Ronald M. Evans

    (Salk Institute for Biological Sciences)

  • Aldons J. Lusis

    (University of California)

  • Markku Laakso

    (University of Eastern Finland)

  • Edward T. Chouchani

    (Dana–Farber Cancer Institute
    Harvard Medical School)

  • Mikael Rydén

    (Karolinska University Hospital)

  • Alan R. Saltiel

    (University of California San Diego
    University of California, San Diego)

Abstract

Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1)1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic β-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or β-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis.

Suggested Citation

  • Omer Keinan & Joseph M. Valentine & Haopeng Xiao & Sushil K. Mahata & Shannon M. Reilly & Mohammad Abu-Odeh & Julia H. Deluca & Benyamin Dadpey & Leslie Cho & Austin Pan & Ruth T. Yu & Yang Dai & Chri, 2021. "Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes," Nature, Nature, vol. 599(7884), pages 296-301, November.
    • Handle: RePEc:nat:nature:v:599:y:2021:i:7884:d:10.1038_s41586-021-04019-8
    DOI: 10.1038/s41586-021-04019-8
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    Cited by:

    1. Qingbo Chen & Lei Huang & Dongning Pan & Kai Hu & Rui Li & Randall H. Friedline & Jason K. Kim & Lihua Julie Zhu & David A. Guertin & Yong-Xu Wang, 2022. "A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Xiaoke Yang & Mingqi Zhu & Xue Lu & Yuxin Wang & Junyu Xiao, 2024. "Architecture and activation of human muscle phosphorylase kinase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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