Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

INRA, AgroParisTech, UMR 914 Nutrition Physiology and Ingestive Behavior, Paris, France Submitted 9 August 2006 ; accepted in final form 1 December 2006 This paper provides molecular evidence for a liver glyconeogenic pathway, that is, a concomitant activation of hepatic gluconeogenesis and glycogenesis, which could participate in the mechanisms that cope with amino acid excess in high-protein (HP) fed rats. This evidence is based on the concomitant upregulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression, downregulation of glucose 6-phosphatase catalytic subunit (G6PC1) gene expression, an absence of glucose release from isolated hepatocytes and restored hepatic glycogen stores in the fed state in HP fed rats. These effects are mainly due to the ability of high physiological concentrations of portal blood amino acids to counteract glucagon-induced liver G6PC1 but not PEPCK gene expression. These results agree with the idea that the metabolic pathway involved in glycogen synthesis is dependent upon the pattern of nutrient availability. This nonoxidative glyconeogenic disposal pathway of gluconeogenic substrates copes with amino excess and participates in adjusting both amino acid and glucose homeostasis. In addition, the pattern of PEPCK and G6PC1 gene expression provides evidence that neither the kidney nor the small intestine participated in gluconeogenic glucose production under our experimental conditions. Moreover, the main glucose-6-phosphatase (G6Pase) isoform expressed in the small intestine is the ubiquitous isoform of G6Pase (G6PC3) rather than the G6PC1 isoform expressed in gluconeogenic organs. high-protein diet; glyconeogenesis; glucose 6-phosphatase; phosphoenolpyruvate carboxykinase; liver Address for reprint requests and other correspondence: D. Tomé, INRA, AgroParisTech, UMR914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, Paris, F75005, France (e-mail: tome{at}agroparistech.fr )