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Adipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice

Author

Listed:
  • Takefumi Kimura

    (National Institute of Diabetes and Digestive and Kidney Diseases
    Shinshu University School of Medicine)

  • Sai P. Pydi

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Lei Wang

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Dhanush Haspula

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Yinghong Cui

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Huiyan Lu

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Gabriele M. König

    (University of Bonn)

  • Evi Kostenis

    (University of Bonn)

  • Gregory R. Steinberg

    (McMaster University)

  • Oksana Gavrilova

    (Mouse Metabolism Core National Institute of Diabetes and Digestive and Kidney Diseases)

  • Jürgen Wess

    (National Institute of Diabetes and Digestive and Kidney Diseases)

Abstract

Obesity is the major driver of the global epidemic in type 2 diabetes (T2D). In individuals with obesity, impaired insulin action leads to increased lipolysis in adipocytes, resulting in elevated plasma free fatty acid (FFA) levels that promote peripheral insulin resistance, a hallmark of T2D. Here we show, by using a combined genetic/biochemical/pharmacologic approach, that increased adipocyte lipolysis can be prevented by selective activation of adipocyte Gq signaling in vitro and in vivo (in mice). Activation of this pathway by a Gq-coupled designer receptor or by an agonist acting on an endogenous adipocyte Gq-coupled receptor (CysLT2 receptor) greatly improved glucose and lipid homeostasis in obese mice or in mice with adipocyte insulin receptor deficiency. Our findings identify adipocyte Gq signaling as an essential regulator of whole-body glucose and lipid homeostasis and should inform the development of novel classes of GPCR-based antidiabetic drugs.

Suggested Citation

  • Takefumi Kimura & Sai P. Pydi & Lei Wang & Dhanush Haspula & Yinghong Cui & Huiyan Lu & Gabriele M. König & Evi Kostenis & Gregory R. Steinberg & Oksana Gavrilova & Jürgen Wess, 2022. "Adipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29231-6
    DOI: 10.1038/s41467-022-29231-6
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    References listed on IDEAS

    as
    1. Sai P. Pydi & Shanu Jain & Wesley Tung & Yinghong Cui & Lu Zhu & Wataru Sakamoto & Shalini Jain & Brent S. Abel & Monica C. Skarulis & Jie Liu & Thanh Huynh & Karel Pacak & Marc G. Caron & Oksana Gavr, 2019. "Adipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Katarina Klepac & Ana Kilić & Thorsten Gnad & Loren M. Brown & Beate Herrmann & Andrea Wilderman & Aileen Balkow & Anja Glöde & Katharina Simon & Martin E. Lidell & Matthias J. Betz & Sven Enerbäck & , 2016. "The Gq signalling pathway inhibits brown and beige adipose tissue," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    3. Lei Wang & Sai P. Pydi & Lu Zhu & Luiz F. Barella & Yinghong Cui & Oksana Gavrilova & Kendra K. Bence & Cecile Vernochet & Jürgen Wess, 2020. "Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    4. Ramona Schrage & Anna-Lena Schmitz & Evelyn Gaffal & Suvi Annala & Stefan Kehraus & Daniela Wenzel & Katrin M. Büllesbach & Tobias Bald & Asuka Inoue & Yuji Shinjo & Ségolène Galandrin & Naveen Shridh, 2015. "The experimental power of FR900359 to study Gq-regulated biological processes," Nature Communications, Nature, vol. 6(1), pages 1-17, December.
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