Peroxisome Proliferator-activated Receptor gamma Activation Promotes Infiltration of Alternatively Activated Macrophages into Adipose Tissue Export

@article{citeulike:3921857, abstract = {Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of proinflammatory mediators, including tumor necrosis factor {alpha} and interleukin-6 (IL-6). Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages toward a more classical and pro-inflammatory phenotype. Here, we explore the effect of peroxisome proliferator-activated receptor {gamma} 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 toward 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 peroxisome proliferator-activated receptor{gamma}-dependent expansion and remodeling of adipose tissue. 10.1074/jbc.M710314200}, author = {Stienstra, Rinke and Duval, Caroline and Keshtkar, Shohreh and van der Laak, Jeroen and Kersten, Sander and Muller, Michael}, citeulike-article-id = {3921857}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M710314200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/283/33/22620}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18541527}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18541527}, day = {15}, doi = {10.1074/jbc.M710314200}, journal = {J. Biol. Chem.}, keywords = {adipose\_tissue, macrophages, ppar-gamma}, month = {August}, number = {33}, pages = {22620--22627}, posted-at = {2009-01-21 21:50:39}, priority = {3}, title = {Peroxisome Proliferator-activated Receptor {gamma} Activation Promotes Infiltration of Alternatively Activated Macrophages into Adipose Tissue}, url = {http://dx.doi.org/10.1074/jbc.M710314200}, volume = {283}, year = {2008} }

TY - JOUR ID - citeulike:3921857 L3 - citeulike-article-id:3921857 N2 - Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of proinflammatory mediators, including tumor necrosis factor {alpha} and interleukin-6 (IL-6). Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages toward a more classical and pro-inflammatory phenotype. Here, we explore the effect of peroxisome proliferator-activated receptor {gamma} 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 toward 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 peroxisome proliferator-activated receptor{gamma}-dependent expansion and remodeling of adipose tissue. 10.1074/jbc.M710314200 IS - 33 JF - J. Biol. Chem. EP - 22627 TI - Peroxisome Proliferator-activated Receptor {gamma} Activation Promotes Infiltration of Alternatively Activated Macrophages into Adipose Tissue VL - 283 SP - 22620 KW - adipose_tissue KW - macrophages KW - ppar-gamma AU - Stienstra, Rinke AU - Duval, Caroline AU - Keshtkar, Shohreh AU - van der Laak, Jeroen AU - Kersten, Sander AU - Muller, Michael PY - 2008/08/15/ UR - http://dx.doi.org/10.1074/jbc.M710314200 ER -