Inflammation in Response to Glucose Ingestion Is Independent of Excess Abdominal Adiposity in Normal-Weight Women with Polycystic Ovary Syndrome

Context: Excess adipose tissue is a source of inflammation. Polycystic ovary syndrome (PCOS) is a proinflammatory state and is often associated with excess abdominal adiposity (AA) alone and/or frank obesity. Objective: To determine the effect of glucose ingestion on cytokine release from mononuclear cells (MNC) in women with PCOS with and without excess AA and/or obesity. Design: A cross-sectional study. Setting: Academic medical center. Patients: Twenty-three women with PCOS (seven normal weight with normal AA, eight normal weight with excess AA, eight obese) and 24 ovulatory controls (eight normal weight with normal AA, eight normal weight with excess AA, eight obese). Intervention: Three-hour 75-g oral glucose tolerance test (OGTT). Main Outcome Measures: Body composition was measured by dual energy x-ray absorptiometry. Insulin sensitivity was derived from the OGTT (ISOGTT). TNFα, IL-6, and IL-1β release was measured in supernatants of cultured MNC isolated from blood samples drawn while fasting and 2 hours after glucose ingestion. Results: Insulin sensitivity was lower in obese subjects regardless of PCOS status and in normal-weight women with PCOS compared with normal-weight controls regardless of body composition status. In response to glucose ingestion, MNC-derived TNFα, IL-6, and IL-1β release decreased in both normal-weight control groups but failed to suppress in either normal-weight PCOS group and in obese women regardless of PCOS status. For the combined groups, the cytokine responses were negatively correlated with insulin sensitivity and positively correlated with abdominal fat and androgens. Conclusions: Women with PCOS fail to suppress MNC-derived cytokine release in response to glucose ingestion, and this response is independent of excess adiposity. Nevertheless, a similar response is also a feature of obesity per se. Circulating MNC and excess adipose tissue are separate and distinct sources of inflammation in this population.

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The proinflammatory TNFα response to glucose ingestion is independent of abdominal adiposity in polycystic ovary syndrome (PCOS)

Fertility and Sterility ◽

10.1016/j.fertnstert.2012.07.223 ◽

2012 ◽

Vol 98 (3) ◽

pp. S63

Author(s):

F. González ◽

C.L. Sia ◽

M.K. Shepard ◽

N.S. Rote ◽

J. Minium

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Abdominal Adiposity ◽

Ovary Syndrome ◽

Glucose Ingestion

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Hyperglycemia-induced oxidative stress is independent of excess abdominal adiposity in normal-weight women with polycystic ovary syndrome

Human Reproduction ◽

10.1093/humrep/des320 ◽

2012 ◽

Vol 27 (12) ◽

pp. 3560-3568 ◽

Cited By ~ 24

Author(s):

F. Gonzalez ◽

C. L. Sia ◽

M. K. Shepard ◽

N. S. Rote ◽

J. Minium

Keyword(s):

Oxidative Stress ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Normal Weight ◽

Abdominal Adiposity ◽

Ovary Syndrome

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Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women

Journal of the Endocrine Society ◽

10.1210/jendso/bvab158 ◽

2021 ◽

Author(s):

Daniel A Dumesic ◽

Ayli Tulberg ◽

Megan McNamara ◽

Tristan R Grogan ◽

David H Abbott ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Elevated Serum ◽

Normal Weight ◽

Model Assessment ◽

Metabolic Function ◽

Ovary Syndrome ◽

Intravenous Glucose

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.

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MON-223 Adipose Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

Journal of the Endocrine Society ◽

10.1210/js.2019-mon-223 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Luis Hoyos ◽

Karen Leung ◽

Tristan Grogan ◽

David Abbott ◽

Gregorio Chazenbalk ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Normal Weight ◽

Ovary Syndrome

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Alarin/FSH Ratio Might Be A New Biological Marker in Polycystic Ovary Syndrome Women with Normal and Women with Obese

Journal of Gynecology & Reproductive Medicine ◽

10.33140/jgrm.03.05.04 ◽

2019 ◽

Vol 3 (5) ◽

Keyword(s):

Luteinizing Hormone ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Biological Marker ◽

Dehydroepiandrosterone Sulfate ◽

Normal Weight ◽

Control Group ◽

Total Testosterone ◽

Ovary Syndrome

Neuropeptides coordinate and regulate physiological processes in all animals. Alarin is a 25 amino acid neuropeptide which promotes the secretion of luteinizing hormone (LH). It has been known that serum luteinizing hormone levels are increased in women with polycystic ovary syndrome. Therefore, purpose of this was to examine the association of circulating gonadotropin secretions, and alarin with women with polycystic ovary syndrome, and to compare these findings with those of control subjects in an effort to better understand the pathophysiology of PCOS. 28 participants with a diagnosis of PCOS with normal weight and 28 participants with a diagnosis of PCOS with obese and 28 control group participants were included in this case-control study. Hormone profiles of the participants (alarin, insulin, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-SO4 ), lipid profiles total testosterone, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol) and fasting blood sugar (FBS) values were measured. Results: Serum androgens were elevated in the PCOS. Blood LH was also elevated (P < 0.05) but was higher in PCOS than Control. Patients with PCOS had an increased alarin compared with controls. LH/FSH ratio and Alarin /FSH ratio were greater than 2.1, 2.4, respectively. The blood alarin levels were significantly correlated with the serum LH levels (r=0.492, p=0.002) and the LH/FSH ratios (r=0.450, p<0.001) and Alarin/ FSH ratios. The FSH/LH and alarin /FSH ratio were elevated in the PCOS. Based on these results, the FSH/LH and Alarin /FSH ratio appears to be a useful marker of PCOS.

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