Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients

Obes Res. 2003 Feb;11(2):176-82. doi: 10.1038/oby.2003.28.


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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue
  • Adult
  • Biliopancreatic Diversion
  • Blood Glucose / analysis
  • Body Composition
  • Body Mass Index
  • Fatty Acids / metabolism
  • Female
  • Gene Expression*
  • Glucose Clamp Technique
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / enzymology
  • Obesity / enzymology*
  • Obesity / surgery
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / analysis


  • Blood Glucose
  • Fatty Acids
  • Insulin
  • Isoenzymes
  • RNA, Messenger
  • Triglycerides
  • Protein Kinases
  • pyruvate dehydrogenase kinase 4