Author Correction: Lkb1 suppresses amino acid-driven gluconeogenesis in the liver.
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ABSTRACT:
SUBMITTER: Just PA
PROVIDER: S-EPMC7969603 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Author Correction: Lkb1 suppresses amino acid-driven gluconeogenesis in the liver.
Just Pierre-Alexandre PA Charawi Sara S Denis Raphaël G P RGP Savall Mathilde M Traore Massiré M Foretz Marc M Bastu Sultan S Magassa Salimata S Senni Nadia N Sohier Pierre P Wursmer Maud M Vasseur-Cognet Mireille M Schmitt Alain A Le Gall Morgane M Leduc Marjorie M Guillonneau François F De Bandt Jean-Pascal JP Mayeux Patrick P Romagnolo Béatrice B Luquet Serge S Bossard Pascale P Perret Christine C
Nature communications 20210317 1
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Project description: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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Project description:Excessive glucose production in the liver is a key factor in the hyperglycemia observed in diabetes mellitus type 2. It is generally agreed to result from an increase in hepatic gluconeogenesis. Considerable attention has been devoted to the transcriptional regulation of key gluconeogenic enzymes, but much less is known about the regulation of amino-acid catabolism, which generates gluconeogenic substrates. Here, we highlight a novel role of 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 was observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion was 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 and pharmacological approaches, we identified the aminotransferases and specifically, Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis. The present dataset is from the phosphoproteomic analysis of fasting mice in a study where a global quantitative analysis ( PXD013478 ) is also described in the same publication.
2020-12-01 | PXD019757 | Pride
Project description:Excessive glucose production in the liver is a key factor in the hyperglycemia observed in diabetes mellitus type 2. It is generally agreed to result from an increase in hepatic gluconeogenesis. Considerable attention has been devoted to the transcriptional regulation of key gluconeogenic enzymes, but much less is known about the regulation of amino-acid catabolism, which generates gluconeogenic substrates. Here, we highlight a novel role of 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 was observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion was 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 and pharmacological approaches, we identified the aminotransferases and specifically, Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis. The present dataset is from the phosphoproteomic analysis of the refed mice in a study where a global quantitative analysis ( PXD013478 ) is also described in the same publication.
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Project description:Excessive hepatic glucose production is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus. It is widely accepted that it is due to an increase in hepatic gluconeogenesis. While much attention has been devoted to the transcriptional regulation of key gluconeogenic enzymes, much less is known about the regulation of amino acid catabolism that provides gluconeogenic substrates. Here, we emphasize a novel role of LKB1 in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have increased hepatic amino acid catabolism for gluconeogenesis. This occurred during fasting, as well as during the postprandial period, identifying Lkb1 as a critical suppressor of hepatic postprandial gluconeogenesis. Hepatic Lkb1 deletion was also associated with severe alterations in whole body metabolism leading to decreased lean body mass deposition on MRI analysis and, at a longer term, cachexia and sarcopenia as a consequence of the diversion of amino acids for liver metabolism at the expense of muscle. Using genetic and pharmacological approaches, we identified the aminotransferases and Agxt and as critical effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.
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