scholarly journals Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Anna M. Fulghesu ◽  
Francesca Sanna ◽  
Sabrina Uda ◽  
Roberta Magnini ◽  
Elaine Portoghese ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
Inflammatory Cytokines ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Low Grade ◽  
Increased Risk ◽  
Altered Immune Response ◽  
Hs Crp ◽  
Activated Monocytes

Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β) and lipokines (leptin, adiponectin), the reactant hs-CRP, andin vitroinflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.

scholarly journals PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiayu Huang ◽  
Lin Liu ◽  
Chunyan Chen ◽  
Ying Gao
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Predictive Biomarker ◽  
Normal Weight ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Model Assessment ◽  
Increased Risk ◽  
Homeostatic Model Assessment ◽  
Low Grade Inflammation

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

scholarly journals Fetuin-A – Alpha2-Heremans-Schmid Glycoprotein: From Structure to a Novel Marker of Chronic Diseases Part 2. Fetuin-A – A Marker of Insulin Resistance and Related Chronic Diseases

2018 ◽  
Vol 11 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Regina S. Komsa-Penkova ◽  
Katya S. Kovacheva ◽  
Georgy M. Golemanov ◽  
Veselin P. Penkov ◽  
Zdravka V. Radionova ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Chronic Diseases ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Fetuin A ◽  
Inflammatory Conditions ◽  
Increased Risk ◽  
Proliferative Signaling

Summary Fetuin-A is a secretory liver glycoprotein with multiple physiological functions such as regulation of insulin resistance, tissue calcification, bone metabolism, cellular proteolytic activity, and self-proliferative signaling. Fetuin-A is a unique molecule which binds to the insulin receptor, modulating its sensitivity, and transducing “the physiological conditions” (serum levels of the metabolites like glucose, free fatty acids, inflammatory signals) from outside into inside the cells. Plasma fetuin-A levels correlate with reduced glucose tolerance and insulin resistance. Impaired insulin sensitivity leads to the development of metabolic syndrome, an increased risk for type 2 diabetes (T2DM), dyslipidaemias and cardiovascular diseases (CVDs). Furthermore, fetuin-A inversely correlates with inflammatory and activation biomarkers, e.g. in patients with T2DM. Thus, circulatory fetuin-A levels may have plausible predictive importance as a biomarker of risk of diabetes and negative acute phase protein. Dysregulated, it plays a crucial role in the pathogenesis of some metabolic disorders and clinical inflammatory conditions like metabolic syndrome, T2DM, CVDs, polycystic ovary syndrome (PCOS), etc.

scholarly journals Clinical Significance of Inflammatory Markers in Polycystic Ovary Syndrome: Their Relationship to Insulin Resistance and Body Mass Index

2009 ◽  
Vol 26 (4) ◽  
pp. 163-170 ◽  
Author(s):  
Nervana Samy ◽  
Maha Hashim ◽  
Magda Sayed ◽  
Mohamed Said
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Inflammatory Markers ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Homa Index ◽  
Risk Markers ◽  
Ovary Syndrome ◽  
Group I ◽  
Hs Crp

Background: Women with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance (IR) and related disorders. Elevated serum levels of high sensitivity CRP (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) reflect low-grade chronic inflammation and have been associated with several insulin-resistant states; they are useful cardiovascular risk markers. The objective of this study was to investigate whether soluble inflammatory markers are altered in PCOS focusing on its relationship with obesity and indexes of insulin resistance.Patients and methods: One hundred and eight women with PCOS and 75 healthy women were recruited. Patients were divided according to body mass index (BMI) into two groups; group I (BMI < 27 kg/m2) and group II (BMI ≥ 27 Kg/m2). Serum levels of hs-CRP, IL-6, and TNF-α, lipid and hormone profiles were measured.Results: PCOS patients had increased levels of testosterone, luteinizing hormone (LH), androstendione, insulin level and HOMA index compared to healthy BMI matched controls. High-density lipoprotein (HDL) concentrations were significantly reduced in both patient groups compared to their controls, while triglyceride levels were significantly increased in obese group compared to controls. There were no significant difference in serum inflammatory markers hs-CRP, IL-6 and TNF-αbetween group I and their matched controls. On the other hand, there were significant increase in these markers between group II and their matched controls. There were highly significant positive correlation between hs-CRP and IL-6 (r= 0.702,P< 0.001) and between hs-CRP and TNF-α(r= 0.621,P<0.001), also between IL-6 and TNF-α(r= 0.543,P< 0.001). These inflammatory markers correlated significantly with BMI and HOMA index. Multiple regression analysis revealed that BMI and HOMA were predictors of IL-6 levels (b= 11.173,P< 0.001,b= 13.564,P< 0.001 respectively) and BMI was the only predictor of hs-CRP levels (b= 12.578,P< 0.001) and TNF-αlevels (b= 0.134,P< 0.001).Conclusion: PCOS and obesity induce an increase in serum inflammatory cardiovascular risk markers. The precise mechanisms underlying these associations require additional studies to clarify the state of the cardiovascular system in women with PCOS compared with controls in large numbers of patients to determine the relative contribution of different factors including insulin resistance, androgen status and BMI.

Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species

2008 ◽  
Vol 294 (3) ◽  
pp. R673-R680 ◽  
Author(s):  
Yongzhong Wei ◽  
Kemin Chen ◽  
Adam T. Whaley-Connell ◽  
Craig S. Stump ◽  
Jamal A. Ibdah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Low Grade ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance ◽  
Increased Risk ◽  
And Oxidative Stress

The cardiometabolic syndrome (CMS), with its increased risk for cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and chronic kidney disease (CKD), has become a growing worldwide health problem. Insulin resistance is a key factor for the development of the CMS and is strongly related to obesity, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), CKD, and NAFLD. Insulin resistance in skeletal muscle is particularly important since it is normally responsible for more than 75% of all insulin-mediated glucose disposal. However, the molecular mechanisms responsible for skeletal muscle insulin resistance remain poorly defined. Accumulating evidence indicates that low-grade chronic inflammation and oxidative stress play fundamental roles in the development of insulin resistance, and inflammatory cytokines likely contribute to the link between inflammation, oxidative stress, and skeletal muscle insulin resistance. Understanding the mechanisms by which skeletal muscle tissue develops resistance to insulin will provide attractive targets for interventions, which may ultimately curb this serious problem. This review is focused on the effects of inflammatory cytokines and oxidative stress on insulin signaling in skeletal muscle and consequent development of insulin resistance.

Women with Polycystic Ovary Syndrome Have Increased Plasma Chitotriosidase Activity: A Pathophysiological Link Between Inflammation and Impaired Insulin Sensitivity?

2012 ◽  
Vol 120 (05) ◽  
pp. 261-265 ◽  
Author(s):  
A. Aydogdu ◽  
I. Tasci ◽  
S. Tapan ◽  
A. Sonmez ◽  
U. Aydogan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Inflammatory Responses ◽  
Polycystic Ovary ◽  
Low Grade ◽  
Model Assessment ◽  
Healthy Controls ◽  
Ovary Syndrome ◽  
Hs Crp ◽  
Chitotriosidase Activity

AbstractPolycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low grade inflammation has been reported to participate in the pathogenesis of insulin resistance. Chitotriosidase (ChT), a protein secreted by activated macrophages, has been shown to be involved in chronic inflammatory responses. In the present study, serum chitotriosidase activity and its relationship with insulin resistance were determined in patients with PCOS.34 patients with PCOS and 44 age and body mass index (BMI) matched healthy controls were enrolled in the study. ChT activity was measured by the fluorescence method. High sensitivity C reactive protein (hs-CRP) and adiponectin levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.Plasma ChT activity, hs-CRP level and HOMA-IR score were significantly higher (p=0.024, p=0.002, p=0.001, respectively) while plasma adiponectin concentration was significantly lower (p=0.018) in women with PCOS compared to healthy controls. Blood ChT activity correlated positively with age, waist-to-hip ratio (WHR), BMI, hs-CRP, HOMA-IR and negatively with blood adiponectin level. After adjustment for age and BMI, ChT activity, total testosterone level and WHR remained as the independent predictors of HOMA-IR score in logistic regression analysis.ChT activity is increased in patients with PCOS in concordance with insulin resistance. These findings may reflect the pronounced risk for metabolic syndrome and atherosclerotic diseases in this particular patient group.

scholarly journals Mangiferin ameliorates insulin resistance in a rat model of polycystic ovary syndrome via inhibition of inflammation

2020 ◽  
Vol 19 (1) ◽  
pp. 89-94
Author(s):  
Qiaohong Qian ◽  
Minjie Tang ◽  
Xinrong Li ◽  
Qi Cao ◽  
Zhiling Zhu
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Serum Glucose ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ovary Syndrome ◽  
Ovarian Weight

Purpose: To examine the effect of mangiferin on insulin resistance (IR) in a rat polycystic ovary syndrome (PCOS) model.Methods: The rat PCOS model was established via subcutaneous injection of 6 mg/kg of dehydroepiandrosterone (DHEA), and mangiferin was orally administered. Body and ovarian weights were recorded. Serum levels of glucose, insulin, and related inflammatory cytokines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay, while the expression levels of key proteins were analyzed by western blotting.Results: DHEA significantly increased ovarian weight and the ratio of ovarian weight/body weight (p <0.001), while mangiferin treatment decreased them (p < 0.001). Mangiferin also lowered DHEA-induced enhancements in serum glucose and insulin levels (p < 0.001). The mRNA and, expression and concentrations of inflammatory cytokines (interleukin-6(IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) were also significantly reduced by mangiferin treatment (p < 0.001). Furthermore, mangiferin suppressed phosphorylation of nuclear factor-kappa B (NF-κB) but increased the phosphorylation of protein kinase B (AKT, p < 0.001).Conclusion: These results reveal that mangiferin not only decreases inflammatory cytokine levels by regulating NF-κB signaling pathway but also ameliorates IR in a rat PCOS model via regulating AKT signaling pathway. Thus, mangiferin is a potential therapeutic strategy for the management of PCOS. Keywords: Polycystic ovary syndrome, Mangiferin, Inflammation, Insulin resistance, NF-κB, AKT

Treatment with Metformin and Combination of Metformin Plus Pioglitazone on Serum Levels of IL-6 and IL-8 in Polycystic Ovary Syndrome: A Randomized Clinical Trial

2019 ◽  
Vol 51 (11) ◽  
pp. 714-722 ◽  
Author(s):  
Durr-e-Shewar Ali ◽  
Mohsin Shah ◽  
Asif Ali ◽  
Muhammad Omar Malik ◽  
Farhat Rehman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Clinical Trial ◽  
Menstrual Cycle ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Serum Levels ◽  
Inflammatory Biomarkers ◽  
Combination Group ◽  
Low Grade ◽  
Ovary Syndrome

AbstractElevated serum levels of inflammatory mediators in conditions such as PCOS reflect a low-grade chronic inflammation and this has been attributed to be associated with insulin-resistance in PCOS. Therefore, insulin-sensitizing agents are suggested to improve both reproductive as well as metabolic aspects of PCOS. This study aimed to compare the effects of metformin taken alone with that of a combination of metformin and pioglitazone on menstrual cycle, hormonal parameters, insulin resistance, and inflammatory biomarkers in women with PCOS. One hundred and six women with PCOS participated in the study. All subjects were randomized into two-arm intervention groups (Arm 1 and 2). Participants in Arm-1 received metformin (500 mg BD) daily while those in Arm-2 a combination of metformin (500 mg BD) and pioglitazone (15 mg BD) for 12 wks. Serum levels of IL-6 and IL-8 were measured using ELISA whereas insulin resistance was assessed using HOMA-IR. At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both the groups, however, only the combination group showed a significant decrease (p=0.005). Serum IL-8 level had a significant decrease after treatment in both groups (p <0.001). HOMA-IR and insulin levels also decreased in both the groups (both p <0.001). Testosterone, FSH, and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.

Metabolic Syndrome During Menopause

2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Natural Menopause ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

scholarly journals Microbiome and PCOS: State-of-Art and Future Aspects

2021 ◽  
Vol 22 (4) ◽  
pp. 2048
Author(s):  
Pierluigi Giampaolino ◽  
Virginia Foreste ◽  
Claudia Di Filippo ◽  
Alessandra Gallo ◽  
Antonio Mercorio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bile Acid ◽  
Peptide Yy ◽  
Fecal Microbiota Transplantation ◽  
Polycystic Ovary ◽  
Current Evidence ◽  
Low Grade ◽  
Fecal Transplant ◽  
Secondary Bile Acid ◽  
First Case

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

2021 ◽  
Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Models ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Reactive Protein ◽  
Reproductive Endocrine ◽  
Factor Α

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.

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