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.
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 obesewomen (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 lipidmalabsorption 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: Shih-Chia Tso; Mingliang Lou; Cheng-Yang Wu; Wen-Jun Gui; Jacinta L Chuang; Lorraine K Morlock; Noelle S Williams; R Max Wynn; Xiangbing Qi; David T Chuang Journal: J Med Chem Date: 2017-01-31 Impact factor: 7.446
Authors: Shih-Chia Tso; Xiangbing Qi; Wen-Jun Gui; Cheng-Yang Wu; Jacinta L Chuang; Ingrid Wernstedt-Asterholm; Lorraine K Morlock; Kyle R Owens; Philipp E Scherer; Noelle S Williams; Uttam K Tambar; R Max Wynn; David T Chuang Journal: J Biol Chem Date: 2013-12-19 Impact factor: 5.157
Authors: Joshua G Leichman; Erik B Wilson; Terry Scarborough; David Aguilar; Charles C Miller; Sherman Yu; Mohamed F Algahim; Manuel Reyes; Frank G Moody; Heinrich Taegtmeyer Journal: Am J Med Date: 2008-11 Impact factor: 4.965
Authors: Andrew J Hoy; Amanda E Brandon; Nigel Turner; Matthew J Watt; Clinton R Bruce; Gregory J Cooney; Edward W Kraegen Journal: Am J Physiol Endocrinol Metab Date: 2009-04-14 Impact factor: 4.310
Authors: Yasmeen Rahimi; João-Paulo G Camporez; Max C Petersen; Dominik Pesta; Rachel J Perry; Michael J Jurczak; Gary W Cline; Gerald I Shulman Journal: Proc Natl Acad Sci U S A Date: 2014-11-03 Impact factor: 11.205