Lkb1 suppresses amino acid-driven gluconeogenesis in the liver

Pierre-Alexandre Just, Sara Charawi, Raphaël G. P. Denis, Mathilde Savall, Massiré Traore, Marc Foretz, Sultan Bastu, Salimata Magassa, Nadia Senni, Pierre Sohier, Maud Wursmer, Mireille Vasseur-Cognet (+10 others)
2020 Nature Communications  
AbstractExcessive 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
more » ... 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.
doi:10.1038/s41467-020-19490-6 pmid:33257663 fatcat:elwo7hgwtze43dw5gprjtf6qji