RESUMO
This is a longitudinal single-arm clinical trial aimed to investigate whether exercise training would modify the whole blood methylation profile in healthy women. A total of 45 subjects were engaged in an exercise training protocol during a 14-wk follow up, consisting of aerobic cardiorespiratory and muscle strength exercises. Subjects were evaluated at baseline (PRE), after 7 wk of exercise training (POST 7), and after 14 wk of exercise training (POST 14). Functional primary outcomes included anthropometric, blood pressure, biochemical measurements, physical tests, and global health assessments. Blood samples were collected at each time point to determine the methylation profile using a DNA methylation array technique screening up to 850k different sites. Exercise training decreased blood pressure and triglyceride levels and enhanced physical performance, including upper- and lower-body maximum strength. Moreover, exercise training improved markers of quality of life. In the array analysis, 14 wk of exercise training changed the methylation of more than 800 sites. Across these differentially methylated sites, we found that differentially methylated sites in the promoter region were more hypermethylated after exercise training, suggesting that this hypermethylation process may affect the transcription process. When inputting the differentially methylated sites in pathway analysis, we found several metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling. This study demonstrates that exercise training promotes a robust change in the whole blood methylation profile and provides new insights into the key regulators of exercise-induced benefits.NEW & NOTEWORTHY We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.
Assuntos
Insulinas , Treinamento Resistido , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Metilação de DNA , Qualidade de Vida , Proteínas Quinases Ativadas por AMP , Exercício Físico/fisiologia , Triglicerídeos , Insulinas/genética , Fator de Crescimento Transformador beta , Treinamento Resistido/métodosRESUMO
Cardiometabolic disorders (CD), including cardiovascular disease (CVD), diabetes, and obesity, are the leading cause of health concern in the United States (U.S.), disproportionately affecting indigenous populations such a Native Hawaiian and Other Pacific Islanders (NHOPI). Dyslipidemia, a prevalent risk factor for the development and progression of CVD, is more prone to occur in NHOPI than other populations in the U.S. High-intensity statin therapy to reduce low-density lipoprotein cholesterol is associated with the prevention of CVD events. However, significant side-effects, such as muscle disorders, have been associated with its use. Different ethnic groups could experience variation in the prevalence of statin side effects due to sociodemographic, behavioral, and/or biological factors. Therefore, identifying the most impactful determinants that can be modified to prevent or reduce statin side effects for individuals from high-risk ethnic minority groups, such as NHOPI, can lead to more effective strategies to reduce health disparities. Thus, our Mini-Review explores the challenging aspects of public health precise strategies in NHOPI taking statins, including a culturally informed additional therapy that could positively impact the NHOPI population.
Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Etnicidade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Grupos Minoritários , Havaiano Nativo ou Outro Ilhéu do Pacífico , Estados UnidosRESUMO
Obesity is among the most alarming health concerns, impacting public health and causing a socioeconomic challenge, especially in developing countries like Brazil, where approximately one quart of the population presents obesity. As an established risk factor for numerous comorbidities with a multifactorial etiology, obesity is a consequence of energy-dense overfeeding, however with significant undernourishment, leading to excessive adipose tissue accumulation and dysfunction, dyslipidemia, and micronutrient deficiencies. About 60% of patients with obesity take statins, a cholesterol-lowering medication, to curb dyslipidemia, with ~10% of these patients presenting various myopathies as side effects. Statins act upon the rate-limiting enzyme of cholesterol biosynthesis in the liver, which is a pathway providing intermediates to the synthesis of selenoproteins, i.e., enzymes containing the micronutrient selenium. Statins have been postulated to negatively impact selenoprotein synthesis, particularly in conditions of selenium deficiency, and potentially implicated in the myopathies occurring as side effects of statins. The Brazilian population is prone to selenium deficiency, hence could be considered more susceptible to statin side effects. This review examines the specific consequences to the Brazilian population of the harmful intersection between obesity development and concomitant micronutrient deficiencies, particularly selenium, combined with statin treatment in the context of nutrition in Brazil.
Assuntos
Dislipidemias/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Obesidade/epidemiologia , Selênio/deficiência , Brasil/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/etiologia , Humanos , Fígado/metabolismo , Estado Nutricional , Obesidade/complicações , Obesidade/metabolismo , Selenoproteínas/biossínteseRESUMO
BACKGROUND & AIMS: The worldwide outbreak of the coronavirus disease 2019 (COVID-19) has already caused a substantial public health burden. Increasing number of studies linked obesity to more severe COVID-19 consequence and mortality, challenging health systems worldwide, especially in emerging countries like Brazil. Herein, we aimed to search the literature and present the current intersection between obesity and COVID-19 in the Brazilian population. METHODS: One hundred twenty-five articles were initially searched after duplicate removal, and nine were finally included in our analysis. RESULTS: Our findings emphasized the magnitude of COVID-19 infection in Brazil and the impact of obesity as a risk factor that aggravates the prognosis of outpatients or hospitalized patients. We also demonstrated social aspects of COVID-19 that could act enhancing the obesity condition in Latin American countries. CONCLUSIONS: A more careful look at the available data could help to understand better the dynamic between obesity and COVID-19, focusing on the Brazilian population and could eventually guide management strategies and therapies for COVID-19 in the future.
Assuntos
COVID-19/epidemiologia , Obesidade/epidemiologia , Brasil/epidemiologia , Comorbidade , Países em Desenvolvimento , Humanos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
People with obesity are often dyslipidemic and prescribed statins to prevent cardiovascular events. A common side effect of statin use is myopathy. This could potentially be caused by the reduction of selenoproteins that curb oxidative stress, in turn, affecting creatine metabolism. We determined if statins regulate hepatic and muscular selenoprotein expression, oxidative stress and creatine metabolism. Mice lacking selenocysteine lyase (Scly KO), a selenium-provider enzyme for selenoprotein synthesis, were fed a high-fat, Se-supplemented diet and treated with simvastatin. Statin improved creatine metabolism in females and oxidative responses in both sexes. Male Scly KO mice were heavier than females after statin treatment. Hepatic selenoproteins were unaffected by statin and genotype in females. Statin upregulated muscular Gpx1 in females but not males, while Scly loss downregulated muscular Gpx1 in males and Selenon in females. Osgin1 was reduced in statin-treated Scly KO males after AmpliSeq analysis. These results refine our understanding of the sex-dependent role of selenium in statin responses.
Assuntos
Fígado/metabolismo , Liases/genética , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Selenoproteínas/metabolismo , Sinvastatina/administração & dosagem , Animais , Creatinina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Músculo Esquelético/efeitos dos fármacos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Selênio , Caracteres Sexuais , Sinvastatina/farmacologia , Glutationa Peroxidase GPX1RESUMO
BACKGROUND: The amino acid selenocysteine (Sec) is an integral part of selenoproteins, a class of proteins mostly involved in strong redox reactions. The enzyme Sec lyase (SCLY) decomposes Sec into selenide allowing for the recycling of the selenium (Se) atom via the selenoprotein synthesis machinery. We previously demonstrated that disruption of the Scly gene (Scly KO) in mice leads to the development of obesity and metabolic syndrome, with effects on glucose homeostasis, worsened by Se deficiency or a high-fat diet, and exacerbated in male mice. Our objective was to determine whether Se supplementation could ameliorate obesity and restore glucose homeostasis in the Scly KO mice. METHODS: Three-weeks old male and female Scly KO mice were fed in separate experiments a diet containing 45 % kcal fat and either sodium selenite or a mixture of sodium selenite and selenomethionine (selenite/SeMet) at moderate (0.25â¯ppm) or high (0.5-1â¯ppm) levels for 9 weeks, and assessed for metabolic parameters, oxidative stress and expression of selenoproteins. RESULTS: Se supplementation was unable to prevent obesity and elevated epididymal white adipose tissue weights in male Scly KO mice. Serum glutathione peroxidase activity in Scly KO mice was unchanged regardless of sex or dietary Se intake; however, supplementation with a mixture of selenite/SeMet improved oxidative stress biomarkers in the male Scly KO mice. CONCLUSION: These results unveil sex- and selenocompound-specific regulation of energy metabolism after the loss of Scly, pointing to a role of this enzyme in the control of whole-body energy metabolism regardless of Se levels.