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The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage

Author

Listed:
  • Romain Girard

    (Université de Sherbrooke)

  • Sarah Tremblay

    (Université de Sherbrooke)

  • Christophe Noll

    (Université de Sherbrooke)

  • Stéphanie St-Jean

    (Université de Sherbrooke)

  • Christine Jones

    (Université de Sherbrooke)

  • Yves Gélinas

    (Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Faculty of Medicine, Université Laval)

  • Faïza Maloum-Rami

    (Université de Sherbrooke)

  • Nathalie Perreault

    (Université de Sherbrooke)

  • Mathieu Laplante

    (Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Faculty of Medicine, Université Laval
    Centre de recherche sur le cancer de l’Université Laval, Université Laval)

  • André C. Carpentier

    (Université de Sherbrooke)

  • François Boudreau

    (Université de Sherbrooke)

Abstract

The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

Suggested Citation

  • Romain Girard & Sarah Tremblay & Christophe Noll & Stéphanie St-Jean & Christine Jones & Yves Gélinas & Faïza Maloum-Rami & Nathalie Perreault & Mathieu Laplante & André C. Carpentier & François Boudr, 2022. "The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27934-w
    DOI: 10.1038/s41467-021-27934-w
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    Cited by:

    1. Nevin Witman & Chikai Zhou & Timm Häneke & Yao Xiao & Xiaoting Huang & Eduarde Rohner & Jesper Sohlmér & Niels Grote Beverborg & Miia L. Lehtinen & Kenneth R. Chien & Makoto Sahara, 2023. "Placental growth factor exerts a dual function for cardiomyogenesis and vasculogenesis during heart development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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