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Reduced PDK4 Expression Associates with Increased Insulin Sensitivity in Postobese Patients
Author(s) -
Rosa Giuseppina,
Rocco Paola,
Manco Melania,
Greco Aldo V.,
Castagneto Marco,
Vidal Hubert,
Mingrone Geltrude
Publication year - 2003
Publication title -
obesity research
Language(s) - English
Resource type - Journals
eISSN - 1550-8528
pISSN - 1071-7323
DOI - 10.1038/oby.2003.28
Subject(s) - pdk4 , medicine , endocrinology , skeletal muscle , insulin , weight loss , insulin sensitivity , body mass index , glucose clamp technique , diabetes mellitus , insulin resistance , lipid metabolism , chemistry , enzyme , obesity , biochemistry , pyruvate dehydrogenase complex
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/m 2 ) 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 ( R 2 = 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.