Insulin Resistance and Lipotoxicity in PCOS: Causes and Consequences

Bellanger, Sylvain; Battista, Marie-Claude; Baillargeon, Jean-Patrice

doi:10.1007/978-1-4614-8394-6_7

Cited by 4 publications

(4 citation statements)

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“…In addition, ceramides produced by the gut microbiota have the potential to pass the epithelial barrier and interact with the host metabolism 32 . Accordingly, it has been proposed that IR and hyperandrogenemia in patients with PCOS could be at least partly driven by an increase in serine phosphorylation due to the accumulation of reactive lipids, such as ceramides, that activate serine kinase signalling pathways 33 . Moreover, it has also been demonstrated that ceramides induce IR via inhibition of Akt signalling in cell cultures 34 .…”

Section: Discussionmentioning

confidence: 99%

“…32 Accordingly, it has been proposed that IR and hyperandrogenemia in patients with PCOS could be at least partly driven by an increase in serine phosphorylation due to the accumulation of reactive lipids, such as ceramides, that activate serine kinase signalling pathways. 33 Moreover, it has also been demonstrated that ceramides induce IR via inhibition of Akt signalling in cell cultures. 34 35 and by stimulating ceramide efflux to the exosome.…”

Section: Discussionmentioning

confidence: 99%

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Gut microbiota in adolescent girls with polycystic ovary syndrome: Effects of randomized treatments

et al. 2020

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Summary Background Girls with obesity and polycystic ovary syndrome (PCOS) and women with PCOS have altered gut microbiota. Objective To study the gut microbiota composition of girls with PCOS without obesity (age, 15.8 years; body mass index [BMI] 25 kg/m2) and the effects of randomized treatments with an oral contraceptive (OC, N = 15) or with spironolactone‐pioglitazone‐metformin (SPIOMET, N = 15) for 1 year. Thirty‐one age‐matched girls served as controls. Methods 16S ribosomal subunit gene amplicon sequencing was performed in stool samples from all subjects; samples from 23 out of 30 girls with PCOS (OC, N = 12; SPIOMET, N = 11) were available for analysis post‐treatment. Clinical and endocrine‐metabolic variables were measured before and after intervention. Results Girls with PCOS had decreased diversity alpha, altered microbiota pattern and taxonomic profile with more abundance of Family XI (P = .002), and less abundance of family Prevotellaceae (P = .0006) the genus Prevotella (P = .0001) and Senegalimassilia (P < .0001), as compared to controls. Family XI abundance related positively to hepato‐visceral fat (R = 0.453; P = .0003). SPIOMET treatment, but not OC, normalized the abundance of Family XI. Prevotellaceae, Prevotella and Senegalimassilia abundance remained unchanged after either treatment. Conclusion SPIOMET's spectrum of normalizing effects in girls with PCOS is herewith broadened as to include Family XI abundance in gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gut microbiota in adolescent girls with polycystic ovary syndrome: Effects of randomized treatments

et al. 2020

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“…Additionally, a qualitative systematic review found evidence for improved insulin sensitivity following exercise in PCOS [17]. An improvement in insulin sensitivity following exercise could therefore be an explanation for both reduced TT and increased SHBG; hyperinsulinemia causes an increase in free androgen plasmatic levels both through the stimulation of ovarian androgen synthesis, and by suppressing hepatic production of SHBG [56]. We were not able to perform a meta-analysis on free testosterone; caution is advised when measuring TT alone, because women with PCOS can have TT in the normal range but have high concentrations of free and bioavailable testosterone due to lower concentrations of SHBG [36].…”

Section: Discussionmentioning

confidence: 99%

The effects of physical exercise on cardiometabolic outcomes in women with polycystic ovary syndrome not taking the oral contraceptive pill: a systematic review and meta-analysis

Woodward

Broom

Harrop

et al. 2019

J Diabetes Metab Disord

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Purpose Women with polycystic ovary syndrome (PCOS) exhibit many metabolic abnormalities that are associated with an increased cardiovascular disease risk. Exercise may promote improvements in lipid profile and insulin sensitivity in women with PCOS. There is however, a knowledge gap on the optimal dose of exercise, regarding duration, intensity, type, and frequency of exercise. The aim of this systematic review and meta-analysis was to define effective types of exercise to improve cardiometabolic profile in PCOS. Methods We included randomised controlled trials (RCT), quasi-RCT, and controlled clinical trials focusing on reproductiveaged women diagnosed with PCOS. Eligible interventions included those with at least two weeks of supervised exercise sessions. Primary outcomes were blood lipids, blood glucose, blood pressure, measures of abdominal adiposity, and inflammation markers. Secondary outcomes were total and free testosterone, sex hormone binding globulin, and measures of insulin resistance. Nine electronic databases were searched from inception to present for English language publications. The Cochrane Risk Assessment tool was used to assess bias in the included studies. Outcomes were quantitatively synthesised and a meta-analysis was performed. Pooled effect estimates and 95% confidence intervals were presented. Results This systematic review identified three trials, including 231 participants with PCOS, that examined the effect of structured, supervised exercise on cardiometabolic outcomes. Analysis of pooled data indicated statistical favourable effects of exercise on total cholesterol, fasting glucose, waist circumference and waist-to-hip ratio, systolic blood pressure, C-reactive protein, total testosterone, and sex hormone binding globulin using post-intervention scores. Conclusions Moderate aerobic exercise interventions ≥3 months in duration, with a frequency of 3/week for at least 30-min, may have favourable effects on various cardiometabolic risk factors in women with PCOS. However, results should be interpreted with caution. Many of the outcomes were based on studies with serious methodological limitations, and only one "gold-standard" RCT was identified. PROSPERO ID: CRD42018086117.

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“…Additionally, a qualitative systematic review found evidence for improved insulin sensitivity following exercise in PCOS (Dewailly, 2016). An improvement in insulin sensitivity following exercise could therefore be an explanation for both reduced TT and increased SHBG; hyperinsulinemia causes an increase in free androgen plasmatic levels both through the stimulation of ovarian androgen synthesis, and by suppressing hepatic production of SHBG (Bellanger, Battista & Baillargeon, 2014). It was not possible to perform a metaanalysis on free testosterone; caution is advised when measuring TT alone, because women with PCOS can have TT in the normal range but have high concentrations of free and bioavailable testosterone due to lower concentrations of SHBG (Karakas, 2017).…”

Section: Secondary Outcomesmentioning

confidence: 99%

Physical activity and cardiovascular disease risk in women with polycystic ovary syndrome

Woodward¹

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Background Polycystic ovary syndrome (PCOS) is a complex, heterogeneous endocrinopathy affecting metabolic, reproductive, and cardiovascular health in women. Evidence indicates that women with PCOS present with a cluster of cardiovascular disease (CVD) risk factors. Physical activity (PA) interventions have been shown to reduce various CVD risk factors in women with PCOS. Research also suggests that sedentary behaviours have a distinct deleterious effect on cardiometabolic health. Thus, increasing PA and reducing sedentary behaviour may be a worthwhile therapeutic target to improve cardiovascular health in women with PCOS. The programme of research presented in this thesis investigates the feasibility and acceptability of two PA interventions to improve markers of CVD risk in women with PCOS using both quantitative and qualitive methods. Methods A systematic review and meta-analysis of the effects of exercise interventions on CVD risk factors in women with PCOS provided an evidence base on which to design a supervised exercise intervention. A feasibility randomised controlled trial (RCT) of two physical activity interventions for women with PCOS was conducted. Participants were randomised to either a supervised exercise intervention, a lifestyle physical activity intervention (LPAG) aimed at reducing sedentary behaviours, or a control group, for 12 weeks. Semi-structured interviews were conducted with a purposive sample of participants from each group on completion of the RCT to explore the acceptability of the interventions, and barriers and facilitators to PA. Results The systematic review and meta-analysis demonstrated that moderate intensity aerobic exercise interventions of ≥three months in duration, with a frequency of three sessions/week, had favourable effects on CVD risk factors. These results informed the design of the RCT. Thirty-six women with PCOS were enrolled onto the feasibility RCT (12 per group). The recruitment rate was 56% and adherence rate to the exercise intervention was considered moderate at 53%. The retention rate was high at 89%, with only five participants lost to follow-up. Adherence to the LPAG was 100%. Two non-serious adverse events were reported in the exercise group, unrelated to trial procedures. For the secondary outcomes, trend data indicates a 14% reduction in oxidised LDL concentrations in the exercise group. In addition, the data indicates weight loss (kg) of 3.4% and 3.6% in the exercise group and the LPAG, respectively. Qualitative data from the interviews (n=11) indicated that the interventions were well received, but acceptability could be improved by providing social connectivity and implementing measures that encourage the adoption of long-term health-promoting behaviours. Conclusions iii The findings suggest that the procedures for recruitment, allocation, and outcome measurements were acceptable. However, adherence to the supervised exercise intervention was below an acceptable rate. The qualitative component provides valuable contextual data that will be crucial to addressing adherence for both the progression to a full-scale RCT, and community interventions for women with PCOS.

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Insulin Resistance and Lipotoxicity in PCOS: Causes and Consequences

Cited by 4 publications

References 97 publications

Gut microbiota in adolescent girls with polycystic ovary syndrome: Effects of randomized treatments

Gut microbiota in adolescent girls with polycystic ovary syndrome: Effects of randomized treatments

The effects of physical exercise on cardiometabolic outcomes in women with polycystic ovary syndrome not taking the oral contraceptive pill: a systematic review and meta-analysis

Physical activity and cardiovascular disease risk in women with polycystic ovary syndrome

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