Mechanisms by Which Metabolic Reprogramming in GSD1 Liver Generates a Favorable Tumorigenic Environment

Abstract Glycogen storage disease type 1 (GSD1) is an inherited disorder caused by impaired glucose 6-phosphatase activity. This impairment translates into the inhibition of endogenous glucose production and the subsequent accumulation of cellular glucose 6-phosphate. Excess glucose 6-phosphate enhances glycolysis, increases the production of fatty acids, uric acid, and lactate, causes hepatomegaly due to glycogen and lipid accumulation, and finally results in liver tumor development. Although the exact mechanisms of tumorigenesis in patients with GSD1 remain unclear, GSD1 hepatocytes undergo ...