Dataset Information

Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

ABSTRACT:

Background

Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS.

Methods

We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR)-adjusted cutoff p < 0.1 to correct for multiple testing. We used miRDB's Gene Ontology (GO) tool to identify predicted pathways for top hits.

Results

Mean age and BMI of participants were 27.9 years and 32.5 kg/m², respectively. Lower levels of miR-1294 were associated with higher waist circumference (β = -0.10, FDR = 0.095). While no miRNAs were associated with HOMA-IR at our FDR cut off <0.1, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at unadjusted p < 0.01, including members of the highly conserved miR-17/92 cluster and miR-1294 (β = -0.10, p < 0.001). The GO analysis of miR-1294 identified 54 overrepresented pathways, including "negative regulation of insulin receptor signaling" (FDR = 0.019), and 6 underrepresented pathways.

Conclusions

Plasma miR-1294 along with members of the miR-17/92 cluster and miRNAs involved in insulin signaling may be associated with central obesity and insulin resistance in PCOS. Larger studies among women with and without PCOS are needed to validate these findings.

SUBMITTER: Wander PL

PROVIDER: S-EPMC9552972 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

Wander Pandora L PL Enquobahrie Daniel A DA Bammler Theo K TK MacDonald James W JW Srinouanprachanh Sengkeo S Kaleru Thanmai T Khakpour Dori D Trikudanathan Subbulaxmi S

Molecular and cellular endocrinology 20220714

<h4>Background</h4>Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS.<h4>Methods</h4>We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput m ...[more]

PMID: 35843386

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Project description:BackgroundWomen with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS.Methods and materialsClinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman® Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease.ResultsWomen with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, padj = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, padj = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling.ConclusionsThese studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is strongly associated with abdominal obesity and insulin resistance and effective approaches to nutrition (e.g., omega-3 fatty acids intake) might improve the cardiometabolic risk profile. This study aimed to examine the associations of dietary and serum omega-3 fatty acids with insulin resistance (IR) and body composition among PCOS patients.MethodsA total of 185 patients with PCOS were included in our analysis. Dietary information was collected through face-to-face interviews using a 102-item food frequency questionnaire (FFQ). Serum omega-3 fatty acid levels were measured with the gas chromatography method. Body composition was measured by both dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance (BIA) methods. The multivariable linear regression model was applied to analyze the associations of dietary and serum omega-3 fatty acids with the levels of Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and body composition parameters among PCOS patients.ResultsOur results indicated that the dietary long-chain omega-3 polyunsaturated fatty acids (PUFA) intakes were negatively associated with HOMA-IR (β = -0.089, P = 0.040), fat mass (β = -0.022, P = 0.047), and body fat percentage (β = -0.026, P = 0.032). For serum biomarkers, higher total omega-3 PUFAs levels (β = -0.158, P = 0.021) and long-chain omega-3 PUFAs levels (β = -0.187, P < 0.001), particularly eicosapentaenoic acid (EPA) (β = -164, P = 0.011) and docosahexaenoic acid (DHA) (β = -0.158, P = 0.001) were also associated with decreased HOMA-IR. In addition, generally, dietary and serum long-chain omega-3 PUFA levels, DPA, and DHA levels were both positively associated with muscle mass measured by DXA; whereas serum total, long-chain and individual omega-3 PUFA levels (e.g., DPA, EPA, and DHA) were all negatively associated with fat mass and body fat percentage. These findings were further confirmed by the findings for body composition measured by the BIA method.ConclusionHigher levels of dietary and serum omega-3 PUFAs, particularly long-chain omega PUFAs (DPA and DHA), might have beneficial effects on metabolic parameters and body composition among PCOS patients.

Dataset Information

Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

Background

Methods

Results

Conclusions

Publications

Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

Similar Datasets

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