Role of FGF21 and GCN2 in mediating the metabolic response to dietary protein restriction

FGF21 is an endocrine signal of protein restriction (PR) and prior data implicate the General Control Nonderepressible 2 (GCN2) kinase as the amino acid sensor linking PR to FGF21 induction. Therefore, we hypothesized that GCN2-deficient mice would fail to respond to reduced dietary protein intake and consequently recapitulate the phenotype of FGF21-deficient mice. C57BL/6J mice (WT), FGF21- and GCN2-deficient mice were fed a control or low protein (LP) diet that was isocaloric by equally varying protein [18% (control) and 4% (LP) of energy] and carbohydrate content while keeping fat content constant. This was o…