Adiponectin decreases pyruvate dehydrogenase kinase 4 gene expression in obese- and diabetic-derived myotubes.
OBJECTIVE
To investigate the effects of globular adiponectin (gAd) on gene expression and whether these effects are mediated through 3',5'-cyclic monophosphate-activated protein kinase in skeletal muscle myotubes obtained from lean, obese and obese diabetic individuals.


METHODS
Rectus abdominus muscle biopsies were obtained from surgical patients to establish primary skeletal muscle cell cultures. Three distinct primary cell culture groups were established (lean, obese and obese diabetic; n = 7 in each group). Once differentiated, these cultures were then exposed to gAd or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) for 6 h.


RESULTS
Stimulation with gAd decreased pyruvate dehydrogenase kinase 4 (PDK4) gene expression in the obese and diabetic samples (p < or = 0.05) and increased cytochrome c oxidase (COX) subunit 4 (COXIV) gene expression in the myotubes derived from lean individuals only (p < 0.05). AICAR treatment also decreased PDK4 gene expression in the obese- and diabetic-derived myotubes (p < or = 0.05) and increased the gene expression of the mitochondrial gene, COXIII, in the lean-derived samples only (p < 0.05).


CONCLUSIONS
This study demonstrated distinct disparity between myotubes derived from lean compared with obese and obese diabetic individuals following gAd and AICAR treatment. Further understanding of the regulation of PDK4 in obese and diabetic skeletal muscle and its interaction with adiponectin signalling is required as this appears to be an important early molecular event in these disease states that may improve blood glucose control and metabolic flux.
McAinch
A J
AJ
School of Biomedical and Health Sciences, Victoria University, PO Box 14428, Melbourne, Victoria 8001, Australia. andrew.mcainch@vu.edu.au
Cameron-Smith
D
D
D052242:Adiponectin / Q000494:pharmacology*; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017568:Rectus Abdominis / Q000166:cytology; D012265:Ribonucleotides / Q000494:pharmacology; D013851:Thinness / Q000378:metabolism; D014739:Victoria
D052242:Adiponectin; D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D003576:Electron Transport Complex IV; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; C031143:AICA ribonucleotide