title: Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome.
abstract: Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation, which can increase the risk of atherogenesis. We examined the effect of glucose ingestion and lipopolysaccharide (LPS) on markers of proatherogenic inflammation in the mononuclear cells (MNC) and plasma of women with PCOS. Sixteen women with PCOS (8 lean, 8 obese) and 15 weight-matched controls (8 lean, 7 obese) underwent a 3-h oral glucose tolerance test (OGTT). Interleukin-6 (IL-6) and interleukin-1β (IL-1β) release from MNC cultured in the presence of LPS and plasma IL-6, C-reactive protein (CRP), and soluble vascular adhesion molecule-1 (sVCAM-1) were measured from blood samples drawn while fasting and 2h after glucose ingestion. Truncal fat was measured by dual-energy absorptiometry (DEXA). Lean women with PCOS and obese controls failed to suppress LPS-stimulated IL-6 and IL-1β release from MNC after glucose ingestion. In contrast, obese women with PCOS suppressed these MNC-derived cytokines under the same conditions. In response to glucose ingestion, plasma IL-6 and sVCAM-1 increased and CRP suppression was attenuated in both PCOS groups and obese controls compared with lean controls. Fasting plasma IL-6 and CRP correlated positively with percentage of truncal fat. The absolute change in plasma IL-6 correlated positively with testosterone. We conclude that glucose ingestion promotes proatherogenic inflammation in PCOS with a systemic response that is independent of obesity. Based on the suppressed MNC-derived cytokine responses suggestive of LPS tolerance, chronic low-grade inflammation may be more profound in obese women with PCOS. Excess abdominal adiposity and hyperandrogenism may contribute to atherogenesis in PCOS.
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: gonzalef@iupui.edu.
authors.forename: Frank
authors.initials: F
authors.lastname: González
authors.affiliation: Departments of Gastroenterology/Hepatology and PathoBiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Rote
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Judi
authors.initials: J
authors.lastname: Minium
authors.affiliation: Helmholtz Zentrum Munchen, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
mesh_terms: D000328:Adult; D000735:Androstenedione / Q000097:blood; D050197:Atherosclerosis / Q000276:immunology*; D001786:Blood Glucose; D001794:Blood Pressure; D001823:Body Composition; D002097:C-Reactive Protein / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007249:Inflammation / Q000276:immunology*; D007328:Insulin / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides; D007986:Luteinizing Hormone / Q000097:blood; D009765:Obesity / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000276:immunology*; D013739:Testosterone / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C508585:IL1B protein, human; C508600:IL6 protein, human; D007328:Insulin; D053583:Interleukin-1beta; D015850:Interleukin-6; D008055:Lipids; D008070:Lipopolysaccharides; D019010:Vascular Cell Adhesion Molecule-1; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate; D007986:Luteinizing Hormone; D002097:C-Reactive Protein; D005947:Glucose
keywords: Abdominal adiposity; Atherosclerosis; Glucose; Hyperandrogenism; Inflammation