TY - JOUR
T1 - Pioglitazone reduces inflammatory responses of human adipocytes to factors secreted by monocytes/macrophages
AU - Permana, Paska A.
AU - Zhang, Weiyang
AU - Wabitsch, Martin
AU - Fischer-Posovszky, Pamela
AU - Duckworth, William C.
AU - Reaven, Peter D.
PY - 2009/5
Y1 - 2009/5
N2 - Infiltration of monocyte-derived macrophages into adipose tissue may contribute to tissue and systemic inflammation and insulin resistance. We hypothesized that pioglitazone (Pio) could specifically reduce the inflammatory response of adipocytes to factors released by monocytes/macrophages. We show that macrophage factors (Mφ-factors) greatly increase expression levels of proinflammatory adipokines, chemokines, and adhesion molecules in human subcutaneous and visceral adipose tissue (SAT and VAT) as well as in adipocytes (up to several hundredfold of control). Compared with SAT, VAT showed enhanced basal and Mφ-factor-induced inflammatory responses. Mφ-factors also induced greater lipolysis in adipocytes, as assessed by concentrations of glycerol released from the cells (196 ± 13 vs. 56 ± 7 μM in control, P < 0.05). Pretreatment of adipose tissue or adipocytes with Pio reduced these responses to Mφ-factors (by 13-86%, P < 0.05) and prevented Mφ-factor suppression of adiponectin expression. Furthermore, Pio pretreatment of adipocytes and macrophages tended to further reduce inflammatory responses of adipocytes to Mφ-factors and monocyte adhesion to Mφ-factor-activated adipocytes. In support of these in vitro data, media conditioned by monocytes isolated from impaired glucose-tolerant subjects treated with Pio (compared with placebo) induced release of lower concentrations of proinflammatory adipokines and glycerol (100 ± 7 vs. 150 ± 15 μM, P < 0.05) from adipocytes. In summary, Pio decreases inflammatory responses in adipose tissue/cells induced by monocytes/macrophages by acting on either or both cell types. These beneficial effects of Pio may attenuate proinflammatory responses resulting from monocyte/macrophage infiltration into adipose tissue and suppress tissue inflammation resulting from the interaction between both cell types.
AB - Infiltration of monocyte-derived macrophages into adipose tissue may contribute to tissue and systemic inflammation and insulin resistance. We hypothesized that pioglitazone (Pio) could specifically reduce the inflammatory response of adipocytes to factors released by monocytes/macrophages. We show that macrophage factors (Mφ-factors) greatly increase expression levels of proinflammatory adipokines, chemokines, and adhesion molecules in human subcutaneous and visceral adipose tissue (SAT and VAT) as well as in adipocytes (up to several hundredfold of control). Compared with SAT, VAT showed enhanced basal and Mφ-factor-induced inflammatory responses. Mφ-factors also induced greater lipolysis in adipocytes, as assessed by concentrations of glycerol released from the cells (196 ± 13 vs. 56 ± 7 μM in control, P < 0.05). Pretreatment of adipose tissue or adipocytes with Pio reduced these responses to Mφ-factors (by 13-86%, P < 0.05) and prevented Mφ-factor suppression of adiponectin expression. Furthermore, Pio pretreatment of adipocytes and macrophages tended to further reduce inflammatory responses of adipocytes to Mφ-factors and monocyte adhesion to Mφ-factor-activated adipocytes. In support of these in vitro data, media conditioned by monocytes isolated from impaired glucose-tolerant subjects treated with Pio (compared with placebo) induced release of lower concentrations of proinflammatory adipokines and glycerol (100 ± 7 vs. 150 ± 15 μM, P < 0.05) from adipocytes. In summary, Pio decreases inflammatory responses in adipose tissue/cells induced by monocytes/macrophages by acting on either or both cell types. These beneficial effects of Pio may attenuate proinflammatory responses resulting from monocyte/macrophage infiltration into adipose tissue and suppress tissue inflammation resulting from the interaction between both cell types.
KW - Adipose
KW - Cross talk
KW - Inflammation
KW - Subcutaneous
KW - Visceral
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U2 - 10.1152/ajpendo.91013.2008
DO - 10.1152/ajpendo.91013.2008
M3 - Article
C2 - 19240250
AN - SCOPUS:66149148932
SN - 0193-1849
VL - 296
SP - E1076-E1084
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5
ER -