TY - JOUR

T1 - Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

AU - Carey, A.

AU - Wolsk, Emil

AU - Bruce, C.

AU - Southgate, R.

AU - Pilegaard, H.

AU - Hawley, John A.

AU - Pedersen, B. K.

AU - Febrario, M.

N1 - Keywords Adipokines - Global gene expression - Type 2 diabetes

PY - 2006

Y1 - 2006

N2 - Aims/hypothesis  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/interpretation  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.

AB - Aims/hypothesis  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/interpretation  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.

U2 - 10.1007/s00125-006-0178-7

DO - 10.1007/s00125-006-0178-7

M3 - Journal article

VL - 49

SP - 1000

EP - 1007

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 5

ER -