PPARgamma agonist induced cardiac enlargement is associated with reduced fatty acid and increased glucose utilization in myocardium of Wistar rats

In toxicological studies, high doses of peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists cause cardiac enlargement. To investigate whether this could be explained by a large shift from free fatty acid to glucose utilization by the heart, Wistar rats were treated for 2-3 weeks with a potent, selective PPARgamma agonist (X334, 3 micromol/kg/d), or vehicle. X334 treatment increased body-weight gain and ventricular mass. Treatment lowered plasma triglycerides by 61 , free fatty acid levels by 72 , insulin levels by 45 , and reduced total plasma protein concentration by 7 (indicating plasma volume expansion) compared to vehicle animals. Fasting plasma glucose levels were unaltered. To assess cardiac free fatty acid and glucose utilization in vivo we used simultaneous infusions of non-beta-oxidizable free fatty acid analogue, [9,10-(3)H](R)-2-bromopalmitate and [U-(14)C]2-deoxy-d-glucose tracers, which yield indices of local free fatty acid and glucose utilization. In anesthetized, 7 h fasted animals, left ventricular glucose utilization was increased to 182 while free fatty acid utilization was reduced by 28 (P