The Mediator complex kinase module is necessary for fructose regulation of liver glycogen levels through induction of glucose-6-phosphatase catalytic subunit (G6pc)

Liver glycogen levels are dynamic and highly regulated by nutrient availability as the levels decrease during fasting and are restored during the feeding cycle. However, feeding in the presence of fructose in water suppressed glycogen accumulation in the liver by up-regulating the expression of glucose-6-phosphatase catalytic subunit (G6pc) gene although the exact mechanism is unknown. We generated liver specific knockout of MED13 mice that lack the transcriptional Mediator complex kinase module to examine its effect on transcriptional activation of inducible target gene expression, such as the ChREBP- and FOXO1-dependent control of the G6pc gene promoter. Overall design: The relative changes in liver expression of lipogenic and gluconeogenic genes as well as glycogen levels were examined in response to fed standard low fat laboratory chow supplemented with water, or water containing sucrose or fructose in control (Med13fl/fl) and liver-specific MED13 knockout (MED13-LKO) mice.