In vitro evidence that hyperglycemia stimulates tumor necrosis factor-α release in obese women with polycystic ovary syndrome

Abstract

Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. The purpose of this study was to determine the effects of hyperglycemia in vitro on tumor necrosis factor (TNF)-release from mononuclear cells (MNC) in PCOS. Twelve reproductive-age women with PCOS (six lean, six obese) and 12 age-matched controls (six lean, six obese) were studied. Insulin sensitivity (IS HOMA ) was estimated from fasting levels of glucose and insulin and percent truncal fat was determined by dual energy absorptiometry (DEXA). TNF release was measured from MNC cultured under euglycemic and hyperglycemic conditions. IS HOMA was higher in obese women with PCOS than in lean women with PCOS (student's t-test; 73·7 14·8 vs 43·1 8·6, P<0·05), but similar to that of obese controls. IS HOMA was positively correlated with percent truncal fat (r=0·57, P<0·04). Obese women with PCOS exhibited an increase in the percent change in TNF release from MNC in response to hyperglycemia compared with obese controls (10 mM, 649 208% vs 133 30%, P<0·003; 15 mM, 799 347% vs 183 59%, P<0·04). The TNF response directly correlated with percent truncal fat (r=0·45, P<0·03) and IS HOMA (r=0·40, P<0·05) for the combined groups, and with plasma testosterone (r=0·60, P<0·05) for women with PCOS. MNC of obese women with PCOS exhibit an increased TNF response to in vitro physiologic hyperglycemia. MNC-derived TNF release may contribute to insulin resistance and hyperandrogenism, particularly when the combination of PCOS and increased adiposity is present.

The adipose cell lineage is not intrinsically insulin resistant in polycystic ovary syndrome

“…Other proinflammatory cytokines have been implicated in the pathogenesis of insulin resistance, including IL-6 [25]. In women with PCOS, circulating TNFα levels have not consistently been found to be elevated [38,39] although mononuclear cells from obese women with PCOS show enhanced TNFα release in response to hyperglycemia compared with controls [40]. Likewise, circulating IL-6 levels do not differ in women with PCOS and age-and BMI-matched controls [41,42].…”

Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome

“…Sixteen women with PCOS (8 lean and 8 obese) 20 -32 yr of age and 16 weight-matched control subjects (8 lean and 8 obese) 20 -40 yr of age volunteered for study participation. Subjects in the present report had been previously involved in our studies on PCOS and insulin resistance, and some largely descriptive data from these subjects included herein have been presented in previous publications (8,9). Obesity was defined as a BMI between 30 and 40 kg/m 2 .…”

“…Waist circumference was measured at the level of the umbilicus and used to estimate abdominal adiposity. In addition, all subjects underwent dual-energy X-ray absorptiometry to determine percent total body fat and percent truncal fat using the QDR 4500 Elite model scanner (Hologic, Waltham, MA) as previously described (9,40).…”

Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major cardiovascular risk factors

“…43 Moreover, it is established that the effect of TNF-α, through activation of the soluble receptors TNFR1 and sTNFR2, is related to components of the metabolic syndrome, 18 such as IGT and type 2 DM(19), higher blood pressure 20 and dyslipidemia, 23 which are common in women with PCOS, even in those with normal BMI. 42,44 As for the inflammatory molecules, data on the relationship between PCOS and carotid intima-media wall thickness (cIMT), a marker of preclinical atherosclerosis, are not conclusive.…”