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Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity

Author

Listed:
  • Lei Wang

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Sai P. Pydi

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Lu Zhu

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Luiz F. Barella

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Yinghong Cui

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Oksana Gavrilova

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Kendra K. Bence

    (Pfizer Inc)

  • Cecile Vernochet

    (Pfizer Inc)

  • Jürgen Wess

    (National Institute of Diabetes and Digestive and Kidney Diseases)

Abstract

Adipocyte dysfunction links obesity to insulin resistance and type 2 diabetes. Adipocyte function is regulated by receptor-mediated activation of heterotrimeric G proteins. Little is known about the potential in vivo metabolic roles of Gi-type G proteins expressed by adipocytes, primarily due to the lack of suitable animal models. To address this question, we generated mice lacking functional Gi proteins selectively in adipocytes. Here we report that these mutant mice displayed significantly impaired glucose tolerance and reduced insulin sensitivity when maintained on an obesogenic diet. In contrast, using a chemogenetic strategy, we demonstrated that activation of Gi signaling selectively in adipocytes greatly improved glucose homeostasis and insulin signaling. We also elucidated the cellular mechanisms underlying the observed metabolic phenotypes. Our data support the concept that adipocyte Gi signaling is essential for maintaining euglycemia. Drug-mediated activation of adipocyte Gi signaling may prove beneficial for restoring proper glucose homeostasis in type 2 diabetes.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16756-x
    DOI: 10.1038/s41467-020-16756-x
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    Cited by:

    1. 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.
    2. Stephen E. Flaherty & Olivier Bezy & Wei Zheng & Dong Yan & Xiangping Li & Srinath Jagarlapudi & Bina Albuquerque & Ryan M. Esquejo & Matthew Peloquin & Meriem Semache & Arturo Mancini & Liya Kang & D, 2023. "Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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