p110α-dependent hepatocyte signaling is critical for liver gene expression and its rewiring in MASLD - Toxicologie Intégrative & Métabolisme
Pré-Publication, Document De Travail Année : 2024

p110α-dependent hepatocyte signaling is critical for liver gene expression and its rewiring in MASLD

Marion Régnier
Prunelle Perrier
  • Fonction : Auteur
Yannick Lippi
Smati Sarra
  • Fonction : Auteur
Céline Lukowicz
  • Fonction : Auteur
Marine Huillet
Cécile Canlet
Sylvie Chevolleau- Mege
  • Fonction : Auteur
Laurent Debrauwer
Walter Wahli
Phillip Hawkins
Nicolas Loiseau

Résumé

Insulin and other growth factors are key regulators of liver gene expression, including in metabolic diseases. Most of the phosphoinositide 3-kinase (PI3K) activity induced by insulin is dependent on PI3Kα. We used mice lacking p110α, the catalytic subunit of PI3Kα, to investigate its role in the regulation of liver gene expression. The absence of hepatocyte PI3Kα signaling promoted glucose intolerance in lean mice and significantly regulated liver gene expression, including insulin-sensitive genes, in ad libitum feeding. Some of the defective regulation of gene expression in response to hepatocyte-restricted insulin receptor deletion was related to PI3Kα signaling. In addition, though PI3Kα deletion in hepatocytes promoted insulin resistance, it was protective against steatotic liver disease in diet-induced obesity. In the absence of hepatocyte PI3Kα, the effect of diet-induced obesity on liver gene expression was significantly altered, with changes in rhythmic gene expression in liver. Therefore, this study highlights the specific role of membrane signaling dependent on hepatocyte PI3Kα in the control of liver gene expression in physiology and in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD).
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hal-04442467 , version 1 (06-02-2024)

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Marion Régnier, Arnaud Polizzi, Tiffany Fougeray, Anne Fougerat, Prunelle Perrier, et al.. p110α-dependent hepatocyte signaling is critical for liver gene expression and its rewiring in MASLD. 2024. ⟨hal-04442467⟩
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