Liver GCN2 controls hepatic FGF21 secretion and modulates whole-body postprandial oxidation profile under a low-protein diet

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Chalvon Demersay, Tristan | Moro, Joanna | Even, Patrick | Chaumontet, Catherine, C. | Tomé, Daniel | Averous, Julien | Piedcoq, Julien | Gaudichon, Claire, C. | Maurin, Anne-Catherine | Fafournoux, Pierre | Dalila, Azzout-Marniche

Edité par CCSD ; American Physiological Society -

Epub ahead of print. OBJECTIVE: GCN2 is a kinase which detects amino acid deficiency and is involved in the control of protein synthesis and energy metabolism. However, the role of hepatic GCN2 in the metabolic adaptations in response to the modulation of dietary protein has been seldom studied. METHODS: Wild-type (WT) and liver GCN2-deficient (KO) mice were fed either a normo-protein diet, a low-protein diet or a high-protein diet for 3 weeks. During this period, body weight, food intake and metabolic parameters were followed. RESULTS: In mice fed normo- and high protein diets, GCN2 pathway in the liver is not activated in WT mice leading to a similar metabolic profile with the one of KO mice. On the contrary, a low protein diet activates GCN2 in WT mice inducing FGF21 secretion. In turn, FGF21 maintains a high level of lipid oxidation leading to a different postprandial oxidation profile compared with KO mice. CONCLUSIONS: Hepatic GCN2 controls FGF21 secretion under a low protein diet, and modulates a whole-body postprandial oxidation profile.

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