Regulation of adiponectin secretion by adipocytes in the polycystic ovary syndrome: role of tumor necrosis factor-{alpha}.
BACKGROUND
Adipose tissue dysfunction associated with low-grade chronic inflammation and dysregulation of adipokine secretion might significantly contribute to the pathogenesis of polycystic ovary syndrome (PCOS).


OBJECTIVE
The objective of the study was to determine whether the effect of TNF-alpha, IL-6, monocyte chemoattractant protein-1, or coculture of adipocytes and adipose tissue macrophages (ATMs), on the secretion of adiponectin by adipocytes, differs in PCOS compared with controls.


METHODS
Primary cultures of sc adipocytes and coculture of adipocytes and ATMs from overweight and obese patients with PCOS and healthy control women were used.


METHODS
Adiponectin secretion by adipocytes was measured.


RESULTS
The baseline secretion of adiponectin by isolated adipocytes did not differ between PCOS and control samples. The net change in adiponectin secretion in response to IL-6, monocyte chemoattractant protein-1, and TNF-alpha differed between PCOS (decreasing) and control (increasing) adipocytes, although the difference reached significance only for TNF-alpha (P < 0.04). Coculture of isolated adipocytes and ATMs resulted in a decrease in adiponectin secretion by PCOS (P < 0.05) but not control adipocytes, and the difference between the net change in adiponectin secretion in PCOS vs. control samples was significant (P < 0.03).


CONCLUSIONS
Our results suggest that adiponectin secretion by adipocytes in response to cytokines/chemokines and most notably in response to coculturing with ATMs differs between PCOS and control women, favoring greater suppression of adiponectin in PCOS. The mechanisms underlying these defects and the role of concurrent obesity remain to be determined.
Chazenbalk
Gregorio
G
Department of Obstetrics and Gynecology and Center for Androgen-Related Disorders, Cedars-Sinai Medical Center, 8635 West Third Street, Suite 160W, Los Angeles, California 90048, USA.
Trivax
Bradley S
BS
Yildiz
Bulent O
BO
Bertolotto
Cristina
C
Mathur
Ruchi
R
Heneidi
Saleh
S
Azziz
Ricardo
R
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D052242:Adiponectin; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha