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Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis

Author

Listed:
  • Eryun Zhang

    (Shanghai University of Traditional Chinese Medicine
    City of Hope National Medical Center)

  • Lihua Jin

    (City of Hope National Medical Center)

  • Yangmeng Wang

    (City of Hope National Medical Center)

  • Jui Tu

    (City of Hope National Medical Center
    City of Hope National Medical Center)

  • Ruirong Zheng

    (Shanghai University of Traditional Chinese Medicine)

  • Lili Ding

    (Shanghai University of Traditional Chinese Medicine
    City of Hope National Medical Center)

  • Zhipeng Fang

    (City of Hope National Medical Center)

  • Mingjie Fan

    (City of Hope National Medical Center)

  • Ismail Al-Abdullah

    (City of Hope National Medical Center)

  • Rama Natarajan

    (City of Hope National Medical Center)

  • Ke Ma

    (City of Hope National Medical Center)

  • Zhengtao Wang

    (Shanghai University of Traditional Chinese Medicine)

  • Arthur D. Riggs

    (City of Hope National Medical Center)

  • Sarah C. Shuck

    (City of Hope National Medical Center)

  • Li Yang

    (Shanghai University of Traditional Chinese Medicine)

  • Wendong Huang

    (City of Hope National Medical Center
    City of Hope National Medical Center)

Abstract

The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5′-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.

Suggested Citation

  • Eryun Zhang & Lihua Jin & Yangmeng Wang & Jui Tu & Ruirong Zheng & Lili Ding & Zhipeng Fang & Mingjie Fan & Ismail Al-Abdullah & Rama Natarajan & Ke Ma & Zhengtao Wang & Arthur D. Riggs & Sarah C. Shu, 2022. "Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28743-5
    DOI: 10.1038/s41467-022-28743-5
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    Cited by:

    1. Eryun Zhang & Alon Agua & Wendong Huang, 2023. "A gut feeling for drugs that have metabolic benefits," Nature Communications, Nature, vol. 14(1), pages 1-4, December.
    2. Ying Yang & Michael A. Reid & Eric A. Hanse & Haiqing Li & Yuanding Li & Bryan I. Ruiz & Qi Fan & Mei Kong, 2023. "SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Song-Yang Zhang & Tony K. T. Lam, 2022. "Metabolic regulation by the intestinal metformin-AMPK axis," Nature Communications, Nature, vol. 13(1), pages 1-3, December.

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