P–589 The effects of vanillic acid on production of testosterone and function of insulin in adipose and ovarian tissues in rat model of polycyctic ovary syndrome

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
H R Nejabati ◽  
V Shahnazi ◽  
M Ghaffar. Novin ◽  
M Nouri
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Vanillic Acid ◽  
Polycystic Ovary ◽  
Vaginal Smear ◽  
Therapeutic Effects ◽  
Model Assessment ◽  
Ovary Syndrome

Abstract Study question What is the possible therapeutic effects of vanillic acid (VA) on the treatment of Polycystic Ovary Syndrome (PCOS)? Summary answer Vanillic acid successfully alleviated metabolic and endocrine abnormalities in adipose and ovarian tissues in a rat model of PCOS. What is known already Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder, is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. In this study, the effects of vanillic acid (VA) on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Study design, size, duration In this study, a letrozole-induced rat model was established and then the experimental groups were treated by VA and MET through oral gavage for one month. Before and after the treatment with drugs, the vaginal smear was carried out . Ovarian and adipose tissues were collected and frozen at − 80 for further analysis following euthanasia of the rats. Participants/materials, setting, methods Thirty Six -week- old Wistar rats were divided into four groups (six rats per each group). Twenty-four rats were received letrozole for five weeks. Then, two experimental groups were treated by metformin (MET), and VA . Serum lipid profile, fasting glucose levels, and hormonal assays were done by corresponding commercial kits. The phosphorylation of AMP-activated protein kinase (AMPK) was detected by western blotting and the expression of studied genes were measured by Real-time PCR. Main results and the role of chance Our results showed that both VA and MET successfully reversed the abnormal estrous cycles of PCOS rats and reduced the serum testosterone levels and Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) gene expression. Furthermore, they improved Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and decreased the serum glucose and triglyceride levels, and gene expression of resisitin. The phosphorylation of AMPK was significantly decreased in adipose and ovarian tissues in PCOS group and both therapeutic factors successfully activated the AMPK in these tissues. However, VA had not such a significant effect in adipose tissue. Limitations, reasons for caution The main limitation of the current study was its design as a rat model, which may have limitation in the translation of knowledge to the clinics. Wider implications of the findings: In summary, to the best of our knowledge, this study is the first study reported beneficial effects of VA on the treatment of PCOS. The findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of the PCOS. Trial registration number 0

scholarly journals Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

2012 ◽  
Vol 167 (5) ◽  
pp. 705-713 ◽  
Author(s):  
Tao Tao ◽  
Shengxian Li ◽  
Aimin Zhao ◽  
Yanyun Zhang ◽  
Wei Liu
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Subcutaneous Adipose Tissue ◽  
Polycystic Ovary ◽  
Mrna Abundance ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Subcutaneous Adipose

Objective Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

Amelioration by quercetin of insulin resistance and uterine GLUT4 and ERα gene expression in rats with polycystic ovary syndrome (PCOS)

2019 ◽  
Vol 31 (2) ◽  
pp. 315 ◽  
Author(s):  
Asma Neisy ◽  
Fatemeh Zal ◽  
Atefeh Seghatoleslam ◽  
Sanaz Alaee
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Glucose Transporter ◽  
Specific Activity ◽  
Polycystic Ovary ◽  
Fasting Blood Glucose ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Metabolic Systems

Insulin resistance (IR) and infertility are two major complications of polycystic ovary syndrome (PCOS), which are the results of changes in certain parts of the reproductive and metabolic systems. We aimed to observe the effect of quercetin on dehydroepiandrosterone (DHEA)-induced PCOS and insulin resistance in rats. All animals were divided into five groups and DHEA was used to induce PCOS. Bodyweight and ovarian morphology of all groups were observed. Fasting blood glucose and insulin levels were analysed. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used for IR level determination. The expression of oestrogen receptor α (ERα) and glucose transporter 4 (GLUT4) genes in the uterus was examined by real-time polymerase chain reaction. Liver hexokinase (HK) and glucokinase (GK) activity was determined using spectrophotometry. Quercetin significantly improved the IR state in PCOS rats. PCOS resulted in a decrease in liver GK and an increase in liver HK specific activity, whereas quercetin increased both liver HK and GK activity. Our data also showed a significant reduction in uterine ERα and GLUT4 expression in the PCOS group, which was increased by quercetin. A remarkable effect of quercetin was the intensive reduction of PCOS-IR and significant induction of uterine GLUT4 and ERα gene expression; it could thus be a possible effective treatment for PCOS and its complications, IR and infertility.

scholarly journals Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Confidence Interval ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Meta Analysis ◽  
Mean Difference ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Synbiotic Supplementation

Objective This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. Results A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. Conclusions Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.

scholarly journals Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4071-4080 ◽  
Author(s):  
Amanda Hurliman ◽  
Jennifer Keller Brown ◽  
Nicole Maille ◽  
Maurizio Mandala ◽  
Peter Casson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Phase 1 ◽  
Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

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

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.

scholarly journals Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Resistance Index ◽  
Total Testosterone ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Ovary Syndrome ◽  
Significant Difference

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.

scholarly journals Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism

2017 ◽  
Vol 39 (05) ◽  
pp. 224-228 ◽  
Author(s):  
Cristina Benetti-Pinto ◽  
Vanessa Piccolo ◽  
Daniela Yela ◽  
Heraldo Garmes
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Thyroid Stimulating Hormone ◽  
Metabolic Parameters ◽  
Overt Hypothyroidism ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Cross Sectional ◽  
Stimulating Hormone

Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 – 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.

scholarly journals Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

2015 ◽  
Vol 61 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Margareth Chiharu Iwata ◽  
Livia Porquere ◽  
Isabel C. Espósito Sorpreso ◽  
Edmund C. Baracat ◽  
José Maria Soares Júnior
Keyword(s):  
Insulin Resistance ◽  
Oral Contraceptive ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Total Testosterone ◽  
Model Assessment ◽  
Cycle Index ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Improve Insulin Resistance

Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

scholarly journals Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

2015 ◽  
Vol 172 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Magdalena Olszanecka-Glinianowicz ◽  
Paweł Madej ◽  
Michał Wdowczyk ◽  
Aleksander Owczarek ◽  
Jerzy Chudek
Keyword(s):  
Insulin Resistance ◽  
Waist Circumference ◽  
Polycystic Ovary Syndrome ◽  
Nutritional Status ◽  
Polycystic Ovary ◽  
Fibroblast Growth Factor 21 ◽  
Model Assessment ◽  
Fat Percentage ◽  
Anthropometric Parameters ◽  
Ovary Syndrome

ObjectiveThe aim of this study was to analyse relationships between plasma fibroblast growth factor 21 (FGF21) levels and nutritional status, and metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) women.Design and settingA cross-sectional study involving 85 PCOS (48 obese) and 72 non-PCOS women (41 obese) was conducted to evaluate the relationship between FGF21 levels and PCOS.MethodsAnthropometric parameters and body composition were determined. In the fasting state; serum concentrations of glucose, androgens, FSH, LH, SHBG, insulin and FGF21 were measured.ResultsPlasma FGF21 levels were significantly higher in obese women compared with normal-weight women in both PCOS and non-PCOS subgroups (120.3 (18.2–698) vs 62.3 (16.4–323.6) pg/ml, P<0.05 and 87.2 (12.9–748.4) vs 62.9 (18.0–378.8) pg/ml, P<0.05 respectively). Additionally, circulating FGF21 levels were significantly higher in the obese PCOS subgroup compared with the non-PCOS subgroup (120.3 (18.2–698.0) vs 87.2 (12.9–748.4) pg/ml, P<0.05). Circulating FGF21 levels were proportional to BMI (R=0.27; P<0.001), body fat mass (R=0.24; P<0.01) and percentage (R=0.24; P<0.01), as well as waist circumference (R=0.26; P<0.01). Additionally, plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were related to FGF21 levels (R=0.44; P<0.001 and R=0.19; P<0.05 respectively). In multiple regression analysis, circulating FGF21 level variability was explained by HOMA-IR values and fat percentage, as well as waist circumference, but not correlated with oestradiol levels and free androgen index values.ConclusionsHigher circulating FGF21 levels are related to nutritional status and insulin resistance independent of PCOS. Increased FGF21 is associated with metabolic but not hormonal disturbances.

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