CONTEXT: Inflammation and excess abdominal adiposity (AA) are often present in normal-weight women with polycystic ovary syndrome (PCOS). OBJECTIVE: We determined the effects of hyperglycemia on nuclear factor-κB (NFκB) activation in mononuclear cells (MNC) of normal-weight women with PCOS with and without excess AA. DESIGN: This was a prospective controlled study. SETTING: The study was conducted at an academic medical center. PATIENTS: Fifteen normal-weight, reproductive-age women with PCOS (seven normal AA, eight excess AA) and 16 body composition-matched controls (eight normal AA, eight excess AA) participated in the study. MAIN OUTCOME MEASURES: Body composition was measured by dual-energy absorptiometry. Insulin sensitivity was derived from an oral glucose tolerance test (IS(OGTT)). Activated NFκB and the protein content of p65 and inhibitory-κB were quantified from MNC, and TNFα and C-reactive protein (CRP) were measured in plasma obtained from blood drawn while fasting and 2 h after glucose ingestion. RESULTS: Compared with controls, both PCOS groups exhibited lower IS(OGTT), increases in activated NFκB and p65 protein, and decreases in inhibitory-κB protein. Compared with women with PCOS with excess AA, those with normal AA exhibited higher testosterone levels and lower TNFα and CRP levels. For the combined groups, the percent change in NFκB activation was negatively correlated with IS(OGTT) and positively correlated with androgens. TNFα and CRP were positively correlated with abdominal fat. CONCLUSION: In normal-weight women with PCOS, the inflammatory response to glucose ingestion is independent of excess AA. Circulating MNC and excess AA are separate and unique sources of inflammation in this population.
CONTEXT: Inflammation and excess abdominal adiposity (AA) are often present in normal-weight women with polycystic ovary syndrome (PCOS). OBJECTIVE: We determined the effects of hyperglycemia on nuclear factor-κB (NFκB) activation in mononuclear cells (MNC) of normal-weight women with PCOS with and without excess AA. DESIGN: This was a prospective controlled study. SETTING: The study was conducted at an academic medical center. PATIENTS: Fifteen normal-weight, reproductive-age women with PCOS (seven normal AA, eight excess AA) and 16 body composition-matched controls (eight normal AA, eight excess AA) participated in the study. MAIN OUTCOME MEASURES: Body composition was measured by dual-energy absorptiometry. Insulin sensitivity was derived from an oral glucose tolerance test (IS(OGTT)). Activated NFκB and the protein content of p65 and inhibitory-κB were quantified from MNC, and TNFα and C-reactive protein (CRP) were measured in plasma obtained from blood drawn while fasting and 2 h after glucose ingestion. RESULTS: Compared with controls, both PCOS groups exhibited lower IS(OGTT), increases in activated NFκB and p65 protein, and decreases in inhibitory-κB protein. Compared with women with PCOS with excess AA, those with normal AA exhibited higher testosterone levels and lower TNFα and CRP levels. For the combined groups, the percent change in NFκB activation was negatively correlated with IS(OGTT) and positively correlated with androgens. TNFα and CRP were positively correlated with abdominal fat. CONCLUSION: In normal-weight women with PCOS, the inflammatory response to glucose ingestion is independent of excess AA. Circulating MNC and excess AA are separate and unique sources of inflammation in this population.
Authors: Stuart P Weisberg; Daniel McCann; Manisha Desai; Michael Rosenbaum; Rudolph L Leibel; Anthony W Ferrante Journal: J Clin Invest Date: 2003-12 Impact factor: 14.808