Fig. 7: Lkb1 controls the hepatic amino acid-driven gluconeogenesis independently of Ampk and likely via the phosphorylation of RNA binding proteins.

a Immunoblot of liver of mutant Ampk mice. Liver of double knockout of Ampkα1 and Ampkα2 catalytic subunits (KO, n = 3) and controls (WT, n = 3) were analyzed by western blot analysis for expression of Ampk, Agxt, Got1, and Gapdh. Representative blot of two independent experiments. b IPA analysis of the significantly deregulated phosphoproteins both in the fasted and refed state. A comprehensive phosphoproteomic analysis of the liver of Lkb1KO^livadmutant and control was performed and the significant differentially expressed phosphoproteins were analyzed for enrichment in GO terms. c Venn diagram comparing the canonical RBP repertoire common to HuH7, HEK293, and Hela cells²⁸ with the significantly DE phosphoproteins of liver of both fasted and refed mutant mice. Enrichment for RBP was done using IPA. d Heatmap of the significantly deregulated phospho-RBP in livers of Lkb1KO^livad and control animals. The phospho-RBP that were shared between the fasted and refed state were highlighted with a red point. Note that most of the phophosites differed and had opposite phosphorylation status between the two nutritional states for most of the phosphoproteins. Heatmap was done using the Genesis software. e Subcellular distribution of Agxt in liver of mutant Lkb1KO^livad and control mice. Subcellular distribution of immunoreactive Agxt was determined by post-embedding protein A gold immuno-electron microscopy. Labeling intensity was obtained by counting the number of gold particles in each organelles. A total of at least 50 fields were analyzed for both the mutant and control liver. Data are represented as means ± SD of two mice per group. P values were determined by unpaired two-tailed t-test. p ≤ 0.0001. f General scheme summarizing how Lkb1 controls liver gluconeogenesis and more specifically the amino acid driven gluconeogenesis. Source data are provided as a Source data file.