PPARgamma activation reduces T-lymphocytes infiltration in adipose tissue

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a major regulator of glucose and lipid metabolism. Furthermore PPARgamma was identified as a key player in inflammation and the development of cardiovascular disease. The role of PPARgamma may expand beyond its primary action in adipose tissue, and involve the regulation of lymphocyte and macrophage infiltration into adipose tissue.

To determine the functional significance of PPARgamma activation in the developement of insulin resistance and adipose tissue inflammation in vivo we undertook studies in HFD (60% kcal from fat)-fed C57BL/6J mice treated for 5 weeks with vehicle (0,5% Tween80/H2O) or 10mg/kg/d rosiglitazone. After 5 weeks of HFD an impairment of the insulin- and glucose metabolism was detected. Insulin sensitivity of HFD mice was reduced by 11%±2,6 (area under the curve (AUC)- insulin tolerance test (ITT)) and glucose tolerance was impaired by 59%±6 (AUC-GTT) (Low fat diet (LFD) vs. HFD, p<0,01). HFD-fed, rosiglitazone-treated mice showed improved insulin sensitivity (15%±1 increase in AUC-ITT vs. HFD-control, p<0,01) and glucose tolerance (24%±9,5 decrease in AUC-ipGTT vs. HFD-control, p<0,01). To assess inflammation markers in gonadal fat during early stage of insulin resistance, we focused on T lymphocyte infiltration in adipose tissue. The T-lymphocyte infiltration marker- CD3gamma – was markedly induced in gonadal fat from HFD-treated mice. At 5 weeks HFD, rosiglitazone intervention led to 77,9% (p<0,05 vs. HFD-control) reduction of CD3gamma expression in adipose tissue from HFD-fed mice. Results were confirmed by immunohistological studies.

The present study demonstrates that pro-inflammatory T-lymphocytes are present in visceral adipose tissue during the initiation of obesity-mediated insulin resistance and may contribute to local inflammatory cell activation. PPARgamma activation results in a reduction of adipose T-lymphocytes which may contribute to the beneficial metabolic actions of PPARgamma ligands.