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Journal articles
Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
Pierre-Alexandre Just
1
Sara Charawi
Raphaël G.P. Denis
2
Mathilde Savall
Massiré Traore
Marc Foretz
3
Sultan Bastu
Salimata Magassa
Nadia Senni
Pierre Sohier
Maud Wursmer
Mireille Vasseur-Cognet
4
Alain Schmitt
Morgane Le Gall
Marjorie Leduc
Francois Guillonneau
Jean-Pascal de Bandt
Patrick Mayeux
Béatrice Romagnolo
Serge Luquet
2
Pascale Bossard
Christine Perret
Pierre-Alexandre Just 1
Author
Sara Charawi
Author
Raphaël G.P. Denis 2
Author
Mathilde Savall
Author
Massiré Traore
Author
Marc Foretz 3
Author IdHAL : marc-foretz ResearcherId : http://www.researcherid.com/rid/O-7334-2017 ORCID : https://orcid.org/0000-0001-7017-9032
Sultan Bastu
Author
Salimata Magassa
Author
Alain Schmitt
Author Employer institution : Institut National de la Santé et de la Recherche Médicale
Morgane Le Gall
Author
Marjorie Leduc
Author
Francois Guillonneau
Author
Pascale P. Bossard
Author
Christine Perret
Author
1
IC UM3 (UMR 8104 / U1016) - Institut Cochin (22 rue Méchain, 75014 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1016 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 8104 (France)
- UP - Université de Paris : UM 3 (85 boulevard Saint-Germain 75006 Paris - France)
2
BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative (Université Paris Diderot, Bât. Buffon, 4 rue Marie-Andrée Lagroua Weill-Hallé, case postale 7081 , 75205 Paris cedex 13 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1133 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR_8251 (France)
- UP - Université de Paris : UMR_8251 (85 boulevard Saint-Germain 75006 Paris - France)
4
IEES (UMR_7618 / UMR_D_242 / UMR_A_1392 / UM_113) - Institut d'écologie et des sciences de l'environnement de Paris (Sorbonne-Université, campus de Jussieu - Bât A - Paris (75005)
Sorbonne-Université, campus de Jussieu - Tour 56/66 - Paris (75005)
AgroParisTech-INRA - Grignon (78)
INRA - Versailles (78)
IRD - Bondy (93)
UPEC - Créteil (94)
- France)
- INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement : UMR_A_1392 (France)
- CNRS - Centre National de la Recherche Scientifique : UMR_7618 (France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 : UMR_7618 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
- SU - Sorbonne Université : UM_113 (21 rue de l’École de médecine - 75006 Paris - France)
- UP - Université de Paris (85 boulevard Saint-Germain 75006 Paris - France)
Abstract : Excessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.
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Journal articles
Complete list of metadatas
https://hal.archives-ouvertes.fr/hal-03031076
Contributor : Marc Foretz <>
Submitted on : Monday, November 30, 2020 - 12:58:06 PM
Last modification on : Tuesday, December 8, 2020 - 3:44:24 AM
Long-term archiving on: : Monday, March 1, 2021 - 6:58:22 PM
Contributor : Marc Foretz <>
Submitted on : Monday, November 30, 2020 - 12:58:06 PM
Last modification on : Tuesday, December 8, 2020 - 3:44:24 AM
Long-term archiving on: : Monday, March 1, 2021 - 6:58:22 PM
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- HAL Id : hal-03031076, version 1
- DOI : 10.1038/s41467-020-19490-6
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UPEC-UPEM | UPEC | IEES | CNRS | INRAE | UP-SANTE | UP-SCIENCES | SU-SCIENCES | UNIV-PARIS | SORBONNE-UNIVERSITE | SU-TI
Citation
Pierre-Alexandre Just, Sara Charawi, Raphaël G.P. Denis, Mathilde Savall, Massiré Traore, et al.. Lkb1 suppresses amino acid-driven gluconeogenesis in the liver. Nature Communications, Nature Publishing Group, 2020, 11 (1), ⟨10.1038/s41467-020-19490-6⟩. ⟨hal-03031076⟩
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