Interestingly, we show that hepatic G6Pase-α deficiency leads to activation of carbohydrate response element-binding protein (ChREBP) signaling, increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) expression, and suppression in PPAR-α expression that all contribute to hepatic steatosis and downregulation of SIRT1 expression. The gene discussed is MLXIPL; the disease is steatosis.