Exercise-induced anti-inflammatory effects in overweight/obese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by exacerbated inflammation, which is implicated in cardiometabolic dysfunction. This study aimed to examine the potential effects of acute exercise on inflammatory responses in obese/overweight PCOS women and their controls. Participants underwent a single bout of moderate-intensity aerobic exercise (30 min at ∼65% of VO2peak). Blood and muscle samples were collected immediately before (PRE) and 60 min after the exercise session. Cytokines (i.e., IL-1ß, IL-6, IL-4, IL-10, TNF-α) were measured both in plasma and in skeletal muscle, and proteins related to inflammatory signaling (IKKα/ß and JNK) were assessed in skeletal muscle. At PRE, PCOS showed elevated muscle TNF-α (+62%, p = 0.0012) and plasma IL-1ß (+76%, p = 0.0010) compared to controls. In PCOS, exercise decreased plasma and muscle TNF-α (-14%, p = 0.0003 and -46%, p = 0.0003), as well as increased plasma and muscle IL-4 (+147%, p = 0.0018 and +62%, p = 0.0474) and plasma IL-10 (+38%, p = 0.0029). Additionally, IKKα/ß and JNK phosphorylation in skeletal muscle, which was higher in PCOS at PRE, was significantly reduced by exercise (-58%, p < 0.0001 and -46%, p < 0.0001, respectively), approaching control levels. Person's correlations between PRE values and delta changes (i.e., exercise effect) showed significant, negative associations for plasma IL-1ß (r = -0.92, p < 0.0001), TNF-α (r = -0.72, p = 0.0100) and IL-6 (r = -0.58, p = 0.05), and muscle TNF-α (r = -0.95, p < 0.0001), IKKα/ß (r = -0.75, p = 0.005), and JNK (r = -0.94, p < 0.0001) in PCOS. In conclusion, exercise can mitigate the inflammatory milieu in women with PCOS. The anti-inflammatory role of exercise could underlie its cardiometabolic protection in PCOS.

Acute exercise elicits differential expression of insulin resistance genes in the skeletal muscle of patients with polycystic ovary syndrome.

OBJECTIVE: This study aimed to explore the role of acute exercise on skeletal muscle gene expression related to insulin resistance in patients with polycystic ovary syndrome (PCOS) and controls. METHODS: Four obese women with PCOS and four body mass index (BMI)-matched controls (CTRL) participated in this study. After an overnight fast, the subjects underwent a single 40-min bout of aerobic exercise. Muscle samples were obtained from vastus lateralis at baseline and 60 min after exercise. The expression of a panel of insulin resistance genes was evaluated by a quantitative PCR array system. Network-based analyses were performed to interpret transcriptional changes occurring before and after the exercise challenge. RESULTS: Overall, differentially expressed genes associated with mitochondria function and peroxisome proliferator-activated receptor signalling were identified. At baseline, there was a significant upregulation of six genes exclusively in PCOS (i.e. NFKBIA, MAPK3, PPARGC1A, GAPDH, ACTB and PPARA). Twelve genes were upregulated in CTRL after a single bout of aerobic exercise (i.e. LEPR, CXCR4, CCR5, IL-18R1, CRLF2, ACACA, CEBPA, PPARGC1A, UCP1, TNFRSF1B, TLR4 and IKBKB). After the exercise session, three genes were upregulated in PCOS (i.e. SOCS3, NAMPT and IL-8), whilst IL-6 was upregulated in both groups after exercise. CONCLUSIONS: This study provides novel evidence on the effects of acute exercise on insulin resistance genes in skeletal muscle of PCOS. The differentially expressed genes reported herein could be further investigated as targets for therapeutic interventions aimed at improving insulin resistance in this syndrome.

Can creatine supplementation form carcinogenic heterocyclic amines in humans?

There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens.

Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue.

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of ß-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Profile of leisure-time physical activity and sedentary behavior in adults in Brazil: a nationwide survey, 2019.

OBJECTIVES: to estimate the prevalence of leisure-time physical activity and sedentary behavior in adults in Brazil. METHODS: this was a cross-sectional, population-based study carried out in a sample of 88,531 Brazilians, using data from the 2019 National Health Survey; leisure-time physical activity (overall and aerobic exercise) was measured according to the World Health Organization guidelines; the weighted prevalence and respective 95% confidence intervals (95%CI) of physical activity, physical inactivity and sedentary behavior were estimated. RESULTS: according to the selected sample, 26.4% (95%CI 25.9;27.1) of Brazilian adults were physically active, 14.0% (95%CI 13.5;14.4) were insufficiently physically active and 59.5% (95%CI 58.8;60.2) were physically inactive; sedentary behavior ≥ 6 hours was reported by 30.1% (95%CI 29.5;30.8) of the population; only 8.6% (95%CI 8.2;8.9) met the recommendations for muscle-strengthening activities. CONCLUSION: most Brazilian adults were physically inactive and did not meet international recommendations for leisure-time physical activity and reduction in sedentary behavior.

Perfil de atividade física no tempo livre e tempo sedentário em adultos no Brasil: inquérito nacional, 2019 / Profile of leisure-time physical activity and sedentary behavior in adults in Brazil: a nationwide survey, 2019 / Perfil de la actividad física en el tiempo libre y sedentario em adultos en Brasil: encuesta nacional, 2019

Objetivos: estimar a prevalência de atividade física no tempo livre e comportamento sedentário em adultos no Brasil. Métodos: estudo seccional, populacional, na amostra de 88.531 brasileiros da Pesquisa Nacional de Saúde de 2019; a atividade física (geral e modalidades aeróbias) no tempo livre foi mensurada conforme as diretrizes da Organização Mundial da Saúde; estimaram-se as prevalências ponderadas, e respectivos intervalos de confiança de 95% (IC95%), de atividade física, inatividade física e tempo sedentário. Resultados: a partir da amostra selecionada, 26,4% (IC95% 25,9;27,1) dos adultos brasileiros eram fisicamente ativos, 14,0% (IC95% 13,5;14,4) eram insuficientemente ativos e 59,5% (IC95% 58,8;60,2) eram inativos; o tempo sedentário ≥ 6 horas foi relatado por 30,1% (IC95% 29,5;30,8) da população; apenas 8,6% (IC95% 8,2;8,9) atenderam às recomendações de atividade física para fortalecimento muscular. Conclusão: a maioria dos brasileiros adultos era inativa e não atendeu às recomendações internacionais de atividade física no tempo livre e restrição de tempo sedentário.

Objectives: to estimate the prevalence of leisure-time physical activity and sedentary behavior in adults in Brazil. Methods: this was a cross-sectional, population-based study carried out in a sample of 88,531 Brazilians, using data from the 2019 National Health Survey; leisure-time physical activity (overall and aerobic exercise) was measured according to the World Health Organization guidelines; the weighted prevalence and respective 95% confidence intervals (95%CI) of physical activity, physical inactivity and sedentary behavior were estimated. Results: according to the selected sample, 26.4% (95%CI 25.9;27.1) of Brazilian adults were physically active, 14.0% (95%CI 13.5;14.4) were insufficiently physically active and 59.5% (95%CI 58.8;60.2) were physically inactive; sedentary behavior ≥ 6 hours was reported by 30.1% (95%CI 29.5;30.8) of the population; only 8.6% (95%CI 8.2;8.9) met the recommendations for muscle-strengthening activities. Conclusion: most Brazilian adults were physically inactive and did not meet international recommendations for leisure-time physical activity and reduction in sedentary behavior.

Objetivos: estimar la prevalencia de actividad física en el tiempo libre y comportamiento sedentario de adultos en Brasil. Métodos: estudio seccional, poblacional, de la muestra de la Encuesta Nacional de Salud de 2019 a partir de lo cual, se estimó la prevalencia ponderada (porcentaje e intervalo de confianza del 95%) de actividad física (general y aeróbica), la inactividad física y el comportamiento sedentario. Resultados: según la muestra elegida, 26,4% (IC95% 25,9;27,1) son físicamente activos, 59,5% (IC95% 58,8;60,2) son inactivos, 14,0% (IC95% 13,5;14,4) son insuficientemente activos y 30,1% (IC95% 29,5;30,8) pasan ≥6 horas sedentarios en su tiempo libre; sólo el 8,6% (IC95% 8,2;8,9) de los adultos cumple con las recomendaciones de actividad física para fortalecimiento muscular. Conclusión: la mayoría de los adultos brasileños son inactivos, no cumplen con las recomendaciones internacionales de actividad física en el tiempo libre y la restricción del tiempo sedentario.

Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major cardiovascular risk factors.

OBJECTIVE: The aim of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) and obesity on circulating markers of low-grade inflammation-tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and high sensitive C-reactive protein (hsCRP)-in young women without major cardiovascular (CV) risk factors (diabetes, dyslipidemia and arterial hypertension). DESIGN: Twenty-five young women with PCOS and 23 eumenorrheic women without major CV risk factors and matched for body mass index (BMI) were studied. They were subdivided according to BMI and PCOS status and comparisons were made between the PCOS and Control groups, regardless of BMI, and between the Obese and Lean groups, regardless of the presence of PCOS. RESULTS: Levels of TNF-α, IL-6 and hsCRP were similar between the PCOS group and the Control group (2.1 vs 1.9 pg/ml, p=0.397, 3.8 vs 5.7 pg/ml, p=0.805 and 0.9 vs 0.5 ng/ml, p=0.361, respectively). Levels of TNF-α were similar between the obese group and the lean group (2.1 vs 1.9 pg/ml, p=0.444). Levels of IL-6 and hsCRP were higher in the obese group than in the lean group (8.7 vs 2.0, p <0.001 and 1.4 vs 0.2 ng/ml, p <0.001, respectively). CONCLUSION: Obesity, but not polycystic ovary syndrome, affects circulating markers of low-grade inflammation in young women without major CV risk factors.

GLUT4 translocation is not impaired after acute exercise in skeletal muscle of women with obesity and polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to examine the effects of acute exercise on insulin signaling in skeletal muscle of women with polycystic ovary syndrome (PCOS) and controls (CTRL). METHODS: Fifteen women with obesity and PCOS and 12 body mass index-matched CTRL participated in this study. Subjects performed a 40-min single bout of exercise. Muscle biopsies were performed before and 60 min after exercise. Selected proteins were assessed by Western blotting. RESULTS: CTRL, but not PCOS, showed a significant increase in PI3-k p85 and AS160 Thr 642 after a single bout of exercise (P = 0.018 and P = 0.018, respectively). Only PCOS showed an increase in Akt Thr 308 and AMPK phosphorylation after exercise (P = 0.018 and P = 0.018, respectively). Total GLUT4 expression was comparable between groups (P > 0.05). GLUT4 translocation tended to be significantly higher in both groups after exercise (PCOS: P = 0.093; CTRL: P = 0.091), with no significant difference between them (P > 0.05). CONCLUSIONS: A single bout of exercise elicited similar GLUT4 translocation in skeletal muscle of PCOS and CTRL, despite a slightly differential pattern of protein phosphorylation. The absence of impairment in GLUT4 translocation suggests that PCOS patients with obesity and insulin resistance may benefit from exercise training.