title: Reduced PDK4 expression associates with increased insulin sensitivity in postobese patients.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Surgery, and Consiglio Nazionale della Ricerca (CNR) Center Catholic University of the Sacred Heart, Rome, Italy. guisi_rosa3@hotmail.com
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rosa
authors.forename: Paola
authors.initials: P
authors.lastname: Di Rocco
authors.forename: Melania
authors.initials: M
authors.lastname: Manco
authors.forename: Aldo V
authors.initials: AV
authors.lastname: Greco
authors.forename: Marco
authors.initials: M
authors.lastname: Castagneto
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Geltrude
authors.initials: G
authors.lastname: Mingrone
mesh_terms: D000273:Adipose Tissue; D000328:Adult; D015904:Biliopancreatic Diversion; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D015992:Body Mass Index; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology; D009765:Obesity / Q000201:enzymology* / Q000601:surgery; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D014280:Triglycerides; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4