PP2A ACTIVATION AND LIQUID FRUCTOSE-INDUCED METABOLIC CHANGES

Introduction. Administration of fructose-enriched diets to rats induces hypertriglyceridemia and hepatic steatosis as a result of reduced PPAR alpha transcriptional activity and partial leptin resistance. In the present work, we studied how fructose alters the control of hepatic energy metabolism at the molecular level. Material and methods. Sixteen Sprague-Dawley male rats were randomised to 2 treatment groups: control and fructose (10% w/v fructose in drinking water for 14 days). Additionally, 12 rats were distributed into 3 groups: control, fructose, and fructose+ AICAR (500 mg/kg/day, in the last 3 days of fructose administration). Plasma levels of triglycerides, glucose, leptin, insulin and adiponectin were measured. Triglyceride and ceramide content, fatty acid beta-oxidation activity, AMPK and PP2A activity and expression of mRNA and protein levels of genes involved in energy metabolism were determined in liver samples. Results. Fructose-fed rats showed high plasma concentrations of triglycerides (x1.3), leptin (x1.9) and adiponectin (x1.7), an increase in hepatic triglycerides (x1.6) and ceramides and in the formation of PPAR alpha-FoxO1 complexes. AICAR administration, despite increasing hepatic AMPK activity (x1.3), modified none of the above mentioned alterations. In livers of non-fasted fructose-fed rats, there was a marked increase in the expression of the catalytic subunit of PP2A (x1.6) and in the binding of ChREBP (x1.4). Conclusions. The deficit in liver fatty acid oxidation induced by fructose ingestion in liquid form is not reversed by the activation of AMPK. PP2A activation by fructose ingestion is the key molecular event in the production of fructose-related metabolic changes.