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Heat therapy improves glucose tolerance and adipose tissue insulin signaling in polycystic ovary syndrome.

ABSTRACT: Polycystic ovary syndrome (PCOS) is associated with high rates of obesity and metabolic dysfunction. Repeated passive heat exposure (termed heat therapy) is a novel lifestyle intervention for improving health in obese women with PCOS. The purpose of this study was to examine changes in metabolic function in obese women with PCOS following heat therapy. Eighteen age- and BMI-matched obese women with PCOS (age: 27?±?1 yr, BMI: 41.3?±?1.1 kg/m-2) were assigned to heat therapy (HT) or time control (CON). HT participants underwent 30 one-hour hot tub sessions over 8-10 wk, while CON participants completed all testing but did not undergo heat therapy. Before (Pre), at the mid-point (Mid), and following (Post) 8-10 wk of heat therapy, metabolic health was assessed using a 2-h oral glucose tolerance test, a subcutaneous abdominal fat biopsy (Pre-Post only), and other blood markers relating to metabolic function. HT participants exhibited improved fasting glucose (Pre: 105?±?3, Post: 89?±?5mg/dl; P = 0.001), glucose area under the curve (AUC) (Pre: 18,698?±?1,045, Post: 16,987?±?1,017 mg·dl-1·min-1; P = 0.028) and insulin AUC (Pre: 126,924?±?11,730, Post: 91,233?±?14,429 IU l-1·min-1; P = 0.012). Adipocyte insulin signaling (p-AKT at Ser-473 with 1.2 nM insulin) increased in HT (Pre: 0.29?±?0.14, Post: 0.93?±?0.29 AU; P = 0.021). Additionally, serum testosterone declined in HT participants (Pre: 51?±?7, Post: 34?±?4 ng/dl; P = 0.033). No parameters changed over time in CON, and no change in BMI was observed in either group. HT substantially improved metabolic risk profile in obese women with PCOS. HT also reduced androgen excess and may improve PCOS symptomology.

SUBMITTER: Ely BR

PROVIDER: S-EPMC7199222 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Heat therapy improves glucose tolerance and adipose tissue insulin signaling in polycystic ovary syndrome.

Ely Brett R BR Clayton Zachary S ZS McCurdy Carrie E CE Pfeiffer Joshua J Needham Karen Wiedenfeld KW Comrada Lindan N LN Minson Christopher T CT

American journal of physiology. Endocrinology and metabolism 20190528 1

Polycystic ovary syndrome (PCOS) is associated with high rates of obesity and metabolic dysfunction. Repeated passive heat exposure (termed heat therapy) is a novel lifestyle intervention for improving health in obese women with PCOS. The purpose of this study was to examine changes in metabolic function in obese women with PCOS following heat therapy. Eighteen age- and BMI-matched obese women with PCOS (age: 27 ± 1 yr, BMI: 41.3 ± 1.1 kg/m<sup>-2</sup>) were assigned to heat therapy (HT) or tim ...[more]

PMID: 31136202

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Project description:Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response.The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment.We conducted an open-label, interventional study at an academic medical center.Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study.Subjects underwent fasting blood sampling, an IV glucose tolerance test, dual-energy x-ray absorptiometry scan, transvaginal ultrasound, and measurement of human chorionic gonadotropin-stimulated androgen levels before and after 12 weeks of treatment with metformin extended release 1500 mg/d. Interval visits were performed to monitor anthropometric measurements and menstrual cycle parameters.Changes in glucose and insulin parameters, androgen levels, anthropometric measurements, and ovulatory menstrual cycles were evaluated.Insulin sensitivity did not change despite weight loss. Glucose effectiveness (P = .002) and the acute insulin response to glucose (P = .002) increased, and basal glucose levels (P = .001) decreased after metformin treatment. T levels also decreased. Women with improved ovulatory function (61%) had lower baseline T levels and lower baseline and stimulated T and androstenedione levels after metformin treatment (all P < .05).Using an IV glucose tolerance test, which distinguishes improvements in glucose effectiveness and insulin sensitivity, metformin does not improve insulin sensitivity in women with PCOS but does improve glucose effectiveness. The improvement in glucose effectiveness may be partially mediated by decreased glucose levels. T levels also decreased with metformin treatment. Ovulation during metformin treatment was associated with lower baseline T levels and greater T and androstenedione decreases during treatment, but not with insulin or LH levels. Thus, the action of metformin in PCOS primarily affects glucose levels and steroidogenesis, which may be mediated by mechanisms that affect both pathways, such as inhibition of mitochondrial complex I.

Project description:Polycystic ovary syndrome (PCOS) is a chronic metabolic disease that is associated with obesity and adipose tissue dysfunction. This study aimed to explore the roles of Dicer (an enzyme that processes primary microRNAs) and microRNAs in PCOS. Protein levels were detected by western blotting, and mRNA and microRNA levels were detected by RT-PCR. Dicer-deficient pre-adipocytes were established by lentiviral transfection, and an miR-223 mimic and miR-223 inhibitor were used to overexpress and inhibit miR-223, respectively. 3T3-L1 cells were induced to differentiate into mature adipocytes by IBMX, insulin, and dexamethasone. The degree of differentiation was determined by oil red O staining. An insulin resistance model was established by exposing mature adipocytes to excessive glucose and insulin. The protein levels of Dicer and Ago2 in adipose tissues of PCOS patients were significantly lower than those in control females. A Dicer-deficient 3T3-L1 cell model was successfully established, whose proliferation was inhibited significantly. Insulin-resistant mature adipocytes expressed significantly less Dicer protein than control cells. The differentiation of Dicer-deficient 3T3-L1 cells and their expression of miR-223 and marker genes associated with adipose differentiation were reduced significantly. Furthermore, 3T3-L1 cells showed a weaker ability to develop into mature adipocytes when miR-223 expression was inhibited. An miR-223 mimic was used to recover the differentiation block induced by Dicer deficiency. This rescued the expression of genes associated with adipose differentiation, although the differentiation block was not efficiently rescued. It is concluded that insulin resistance may contribute to the decreased levels of Dicer protein in adipose tissue of PCOS patients. This suggests that dysfunction of Dicer plays a significant role in obesity of PCOS patients. miR-223 is a key factor in Dicer-regulated adipose differentiation, and other microRNAs may be involved in the process.

Dataset Information

Heat therapy improves glucose tolerance and adipose tissue insulin signaling in polycystic ovary syndrome.

Publications

Heat therapy improves glucose tolerance and adipose tissue insulin signaling in polycystic ovary syndrome.

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