Differential regulation of adiponectin receptor gene expression by adiponectin and leptin in myotubes derived from obese and diabetic individuals.
OBJECTIVE
This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin.


METHODS
Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 microg/mL) or leptin (2.5 microg/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real-time polymerase chain reaction analysis.


RESULTS
AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8-fold and 2.5-fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups.


CONCLUSIONS
Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese-prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.
McAinch
Andrew J
AJ
School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, Victoria 3125, Australia.
Steinberg
Gregory R
GR
Mollica
Janelle
J
O'Brien
Paul E
PE
Dixon
John B
JB
Macaulay
S Lance
SL
Kemp
Bruce E
BE
Cameron-Smith
David
D
D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D015431:Weight Loss / Q000502:physiology
C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; C515448:LEPR protein, human; D020738:Leptin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin