Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients

Objective: The aim of this study was to verify whether changes in PDK4 mRNA expression in skeletal muscle in formerly obese subjects who underwent malabsorptive bariatric surgery [bilio-pancreatic diversion (BPD)] might be related to insulin sensitivity improvement, and if these possible modifications might correlate with a reduction of the intramyocytic lipid level. Research Methods and Procedures: Six obese women (body mass index 46.6 ± 8.2 kg/m²) were enrolled in the study. Body composition, euglycemic-hyperinsulinemic clamp and muscle biopsies for skeletal muscle lipid analysis, and semiquantitative reverse transcriptase-polymerase chain reaction were performed before and 3 years after BPD. Results: The average weight loss observed after surgery was ∼42%. Increased glucose uptake was accompanied by a significant decrease of PDK4 mRNA (R² = 0.71, p <0.001). The amounts of intramyocytic triglycerides correlate directly with PDK4 mRNA (R ² = 0.87, p = 0.005) and inversely with glucose uptake values (R ² = 0.75, p <0.001). Discussion: Our results support the concept that a reduced tissue availability of fatty acids consequent to a massive lipid malabsorption influences glucose metabolism acting through the regulation of PDH complex. In fact, as shown in animals, a higher level of FFA availability is likely to induce overexpression of PDK4 also in humans.