Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated macrophage chemotaxis and recruitment.
The link between intra-abdominal adiposity and type II diabetes has been known for decades, and adipose tissue macrophage (ATM)-associated inflammation has recently been linked to insulin resistance. However, the mechanisms associated with ATM recruitment remain ill defined. Herein, we describe in vitro chemotaxis studies, in which adipocyte conditioned medium was used to stimulate macrophage migration. We demonstrate that tumor necrosis factor alpha and free fatty acids, key inflammatory stimuli involved in obesity-associated autocrine/paracrine inflammatory signaling, stimulate adipocyte expression and secretion of macrophage chemoattractants. Pharmacological studies showed that peroxisome proliferator-activated receptor gamma agonists and glucocorticoids potently inhibit adipocyte- induced recruitment of macrophages. This latter effect was mediated by the glucocorticoid receptor, which led to decreased chemokine secretion and expression. In vivo results were quite comparable; treatment of high fat diet-fed mice with dexamethasone prevented ATM accumulation in epididymal fat. This decrease in ATM was most pronounced for the proinflammatory F4/80(+), CD11b(+), CD11c(+) M-1-like ATM subset. Overall, our results elucidate a beneficial function of peroxisome proliferator-activated receptor gamma activation and glucocorticoid receptor/glucocorticoids in adipose tissue and indicate that pharmacologic prevention of ATM accumulation could be beneficial.
Patsouris
David
D
Division of Endocrinology-Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Neels
Jaap G
JG
Fan
WuQiang
W
Li
Ping-Ping
PP
Nguyen
M T Audrey
MT
Olefsky
Jerrold M
JM
D017667:Adipocytes / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha