p110alpha-dependent hepatocyte signaling is critical for liver gene expression and its rewiring in MASLD
p110alpha-dependent hepatocyte signaling is critical for liver gene expression and its rewiring in MASLD
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 PI3Kalpha. We used mice lacking p110alpha, the catalytic subunit of PI3Kalpha, to investigate its role in the regulation of liver gene expression. The absence of hepatocyte PI3Kalpha; 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 PI3Kalpha; signaling. In addition, though PI3Kalpha; deletion in hepatocytes promoted insulin resistance, it was protective against steatotic liver disease in diet-induced obesity. In the absence of hepatocyte PI3Kalpha, 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 PI3Kalpha; in the control of liver gene expression in physiology and in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD).
Regnier Marion、Blum Yuna、Debrauwer Laurent、Levade Thierry、Gourdy Pierre、Wahli Walter、Gamet-Payrastre Laurence、Hawkins Phillip、Montagner Alexandra、Loiseau Nicolas、Polizzi Arnaud、Anderson Karen、Lasserre Frederic、Fouche Edwin、Huillet Marine、Tramunt Blandine、Bertrand-Michel Justine、Perrier Prunelle、Guillermet-Guibert Julie、Rousseau-Bacquie Elodie、Smati Sarra、Stephens Len、Heymes Christophe、Fougeray Tiffany、Chevolleau-Mege Sylvie、Garcia Geraldine、Naylies Claire、Lippi Yannick、Lukowicz Celine、Fougerat Anne、Guillou Herve、Ellero-Simatos Sandrine、Rives Clemence、Burcelin Remy、Canlet Cecile
基础医学生理学生物化学
Regnier Marion,Blum Yuna,Debrauwer Laurent,Levade Thierry,Gourdy Pierre,Wahli Walter,Gamet-Payrastre Laurence,Hawkins Phillip,Montagner Alexandra,Loiseau Nicolas,Polizzi Arnaud,Anderson Karen,Lasserre Frederic,Fouche Edwin,Huillet Marine,Tramunt Blandine,Bertrand-Michel Justine,Perrier Prunelle,Guillermet-Guibert Julie,Rousseau-Bacquie Elodie,Smati Sarra,Stephens Len,Heymes Christophe,Fougeray Tiffany,Chevolleau-Mege Sylvie,Garcia Geraldine,Naylies Claire,Lippi Yannick,Lukowicz Celine,Fougerat Anne,Guillou Herve,Ellero-Simatos Sandrine,Rives Clemence,Burcelin Remy,Canlet Cecile.p110alpha-dependent hepatocyte signaling is critical for liver gene expression and its rewiring in MASLD[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2024.01.09.574858.点此复制
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