Research Output per year
Background: Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of pro-inflammatory mediators, including TNFalpha and IL-6. Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages towards a more classical and pro-inflammatory phenotype. Here, we explore the effect of PPARγ-activation on obesity-induced inflammation in 129SV mice fed a high fat diet for 20 weeks. High fat feeding increased bodyweight gain, adipose tissue mass and liver triglycerides. Rosiglitazone treatment further increased adipose mass, reduced liver triglycerides and changed adipose tissue morphology towards smaller adipocytes. Surprisingly, rosiglitazone markedly increased the number of macrophages in adipose tissue, as shown by immunohistochemical analysis and quantification of macrophage marker genes CD68 and F4/80+. In adipose tissue, markers for classically activated macrophages including IL-18 were down regulated whereas markers characteristic for alternatively activated macrophages (Arginase 1, IL-10) were up regulated by rosiglitazone. Importantly, conditioned media from rosiglitazone-treated alternatively activated macrophages neutralized the inhibitory effect of macrophages on 3T3-L1 adipocyte differentiation, suggesting that alternatively activated macrophages may be involved in mediating the effects of rosiglitazone on adipose tissue morphology and mass. Our results suggest that short term rosiglitazone treatment increases infiltration of alternatively activated macrophages in adipose tissue. The alternatively activated macrophages might play a role in PPARγ-dependent expansion and remodeling of adipose tissue.
|Date made available||29 Apr 2008|
Peroxisome Proliferator-activated Receptor - Activation Promotes Infiltration of Alternatively Activated Macrophages into Adipose TissueStienstra, R., Duval, C. N. C., Keshtkar Ghiasabadi, S., van der Laak, J., Kersten, A. H. & Müller, M. R., 2008, In : Journal of Biological Chemistry. 283, 33, p. 22620-22627
Research output: Contribution to journal › Article › Academic › peer-review
Stienstra, R. (Creator), Duval, C. N. C. (Creator), Keshtkar, S. (Creator), van der Laak, J. (Creator), Kersten, S. (Creator), Muller, M. (Creator) (29 Apr 2008). PPARγ activation promotes infiltration of alternatively activated macrophages into adipose tissue. Wageningen University.