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Pioglitazone induces apoptosis of macrophages in human adipose tissue.
- Source :
-
Journal of lipid research [J Lipid Res] 2006 Sep; Vol. 47 (9), pp. 2080-8. Date of Electronic Publication: 2006 Jun 23. - Publication Year :
- 2006
-
Abstract
- Metabolic syndrome and type 2 diabetes mellitus are associated with an increased number of macrophage cells that infiltrate white adipose tissue (WAT). Previously, we demonstrated that the treatment of subjects with impaired glucose tolerance (IGT) with the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone resulted in a decrease in macrophage number in adipose tissue. Here, adipose tissue samples from IGT subjects treated with pioglitazone were examined for apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. TUNEL-positive cells were identified, and there was a significant 42% increase in TUNEL-positive cells following pioglitazone treatment. Overlay experiments with anti-CD68 antibody demonstrated that most of the TUNEL-positive cells were macrophages. To determine whether macrophage apoptosis was a direct or indirect effect of pioglitazone treatment, human THP1 cells were treated with pioglitazone in vitro, demonstrating increased TUNEL staining in a dose- and time-dependent manner. Furthermore, the appearance of the active proteolytic subunits of caspase-3 and caspase-9 were detected in cell lysate from THP1 cells and also increased in a dose- and time-dependent manner following pioglitazone treatment. Pretreatment with a PPARgamma inhibitor, GW9662, prevented pioglitazone induction of the apoptotic pathway in THP1 cells. Differentiated human adipocytes did not show any significant increase in apoptosis after treatment in vitro with piolgitazone. These findings indicate that PPARgamma has distinct functions in different cell types in WAT, such that pioglitazone reduces macrophage infiltration by inducing apoptotic cell death specifically in macrophages through PPARgamma activation.
- Subjects :
- Adipocytes cytology
Adipocytes drug effects
Adipocytes metabolism
Adipose Tissue cytology
Adipose Tissue metabolism
Anilides pharmacology
Antigens, CD analysis
Antigens, Differentiation, Myelomonocytic analysis
CD36 Antigens analysis
CD36 Antigens genetics
Caspase 3
Caspase 9
Caspases metabolism
Cell Differentiation drug effects
Cell Line
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Hypoglycemic Agents pharmacology
Immunohistochemistry
In Situ Nick-End Labeling
Macrophages cytology
Macrophages metabolism
PPAR gamma agonists
PPAR gamma antagonists & inhibitors
PPAR gamma metabolism
Pioglitazone
Adipose Tissue drug effects
Apoptosis drug effects
Macrophages drug effects
Thiazolidinediones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2275
- Volume :
- 47
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 16799131
- Full Text :
- https://doi.org/10.1194/jlr.M600235-JLR200