Academic Journal
Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
| العنوان: | Lkb1 suppresses amino acid-driven gluconeogenesis in the liver |
|---|---|
| المؤلفون: | Just, Pierre-Alexandre, Charawi, Sara, Denis, Raphaël, Savall, Mathilde, Traore, Massiré, Foretz, Marc, Bastu, Sultan, Magassa, Salimata, Senni, Nadia, Sohier, Pierre, Wursmer, Maud, Vasseur-Cognet, Mireille, Schmitt, Alain, Le Gall, Morgane, Leduc, Marjorie, Guillonneau, François, de Bandt, Jean-Pascal, Mayeux, Patrick, Romagnolo, Béatrice, Luquet, Serge, Bossard, Pascale, Perret, Christine |
| المساهمون: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme (PRETRRAM (URP_4466)), Université Paris Cité (UPCité), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| المصدر: | ISSN: 2041-1723. |
| بيانات النشر: | CCSD Nature Publishing Group |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33257663; PUBMED: 33257663; WOS: 000617695100010 |
| DOI: | 10.1038/s41467-020-19490-6 |
| الاتاحة: | https://hal.science/hal-03097133 https://hal.science/hal-03097133v1/document https://hal.science/hal-03097133v1/file/41467_2020_Article_19490.pdf https://doi.org/10.1038/s41467-020-19490-6 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.60DDD53A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-19490-6 |
|---|