Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion.
OBJECTIVE
We compared metabolic gene expression in adipose tissue and skeletal muscle from patients with type 2 diabetes and from well-matched healthy control subjects. We hypothesised that gene expression would be discordantly regulated when comparing the two groups. Our secondary aim was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR.


METHODS
Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset of these individuals underwent a 3-h infusion of recombinant human IL6 and had adipose tissue samples taken before and after infusion.


RESULTS
The mRNA gene expression of suppressor of cytokine signalling (SOCS) 3, peroxisome proliferative activated receptor (PPAR) alpha/delta, PPAR gamma, coactivator 1, alpha (PPARGC1A), carnitine palmitoyltransferase 1B and solute carrier family 2 (facilitated glucose transporter), member 4 (formerly known as glucose transporter 4/GLUT4), was higher in adipose tissue, but lower in skeletal muscle of diabetic patients than in that of control subjects. In addition, uncoupling protein 1 (UCP1) gene was detected in the adipose tissue of some of the diabetic patients, but not in the control subjects. The following genes were increased by infusion of recombinant human IL6 in both groups: SOCS1/3, resistin, adiponectin, AMP-activated protein kinase-alpha-1 and PPARA. Plasma tumour necrosis factor alpha, adiponectin and resistin were all unaffected by IL6 infusion, but plasma resistin was lower in the diabetic subjects than in control subjects.


CONCLUSIONS
The observation that PPARGC1A and the PPARs were upregulated in the adipose tissue of type 2 diabetic patients, along with the finding that adipose tissue from some patients with type 2 diabetes can express UCP1 mRNA, suggests that in these patients white adipose tissue may move towards a brown adipose tissue phenotype.
Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, RMIT University, Bundoora, VIC, Australia.
A L
AL
Carey
E Wolsk
EW
Petersen
C R
CR
Bruce
R J
RJ
Southgate
H
H
Pilegaard
J A
JA
Hawley
B K
BK
Pedersen
M A
MA
Febbraio
D052242:Adiponectin / Q000235:genetics; D000273:Adipose Tissue / Q000503:physiopathology*; D001706:Biopsy; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007301:Insect Hormones / Q000235:genetics; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009842:Oligopeptides / Q000235:genetics; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D052242:Adiponectin; D007301:Insect Hormones; D015850:Interleukin-6; D009842:Oligopeptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C044833:adipokinetic hormone; D011761:Pyrrolidonecarboxylic Acid