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mTOR, AMPK and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to amino acids and insulin.
Author(s) -
Tomé Daniel,
Chotechuang Nattida,
AzzoutMarniche Dalila,
Chaumontet Catherine,
Bos Cécile,
Gausserès Nicolas,
Gaudichon Claire
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.228.2
Subject(s) - ampk , pi3k/akt/mtor pathway , insulin , chemistry , amino acid , phosphorylation , mechanistic target of rapamycin , rptor , protein kinase a , protein biosynthesis , metabolism , adenosine triphosphate , biochemistry , medicine , endocrinology , signal transduction , biology
This study addressed the question of amino acid sensing in hepatocytes. We investigated the influence of amino acid mixture and insulin on the phosphorylation state of mammalian target of rapamycin (P‐mTOR), adenosine monophosphate‐activated protein kinase (P‐AMPK) and general control non depressible 2 kinase (P‐GCN2)in primary culture of hepatocytes. The activation of protein translation required both high AA levels and insulin, as indicated by the increase in 4E‐BP1 phosphorylation (Pƒ¬0.01). This was associated with an increase in P‐mTOR and a reduction of the activity of P‐AMPK and P‐GCN2 (Pƒ¬0.01) suggesting, for the first time, that GCN2 is involved in sensing amino acids increase. In order to examine whether 4E‐BP1 is the down stream target of mTOR, hepatocytes were incubated in the presence or absence of AICAR or Rapamycin. Surprisingly, no change in p4E‐BP1 was observed in the presence of Rapamycin whereas p4EBP‐1 was dramatically decreased by AIRCAR. This suggested that in response to AA and insulin 4E‐BP1 is not the direct downstream target of mTOR and that AMPK may be involved in this effect.