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.


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.
Rosa
Giuseppina
G
Department of Internal Medicine, Surgery, and Consiglio Nazionale della Ricerca (CNR) Center Catholic University of the Sacred Heart, Rome, Italy. guisi_rosa3@hotmail.com
Di Rocco
Paola
P
Manco
Melania
M
Greco
Aldo V
AV
Castagneto
Marco
M
Vidal
Hubert
H
Mingrone
Geltrude
G
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
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D014280:Triglycerides; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4