Effects of Moderate-Intensity Physical Training on Skeletal Muscle Substrate Transporters and Metabolic Parameters of Ovariectomized Rats.

A deficit of estrogen is associated with energy substrate imbalance, raising the risk of metabolic diseases. Physical training (PT) is a potent metabolic regulator through oxidation and storage of substrates transported by GLUT4 and FAT CD36 in skeletal muscle. However, little is known about the effects of PT on these carriers in an estrogen-deficit scenario. Thus, the aim of this study was to determine the influence of 12 weeks of PT on metabolic variables and GLUT4 and FAT CD36 expression in the skeletal muscle of animals energetically impaired by ovariectomy (OVX). The trained animals swam 30 min/day, 5 days/week, at 80% of the critical load intensity. Spontaneous physical activity was measured biweekly. After training, FAT CD36 and GLUT4 expressions were quantified by immunofluorescence in the soleus, as well as muscular glycogen and triglyceride of the soleus, gluteus maximus and gastrocnemius. OVX significantly reduced FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01), while PT significantly increased FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01). PT increased soleus glycogen, and OVX decreased muscular triglyceride of gluteus maximus. Therefore, OVX can cause energy disarray through reduction in GLUT4 and FAT CD36 and their muscle substrates and PT prevented these metabolic consequences, masking ovarian estrogen's absence.

Short-term effects induced by nicotinamide in ovariectomized females.

Nicotinamide adenine dinucleotide (NAD)+ precursors such as nicotinamide activate sirtuins and enhance energy metabolism. The aim of this study was to evaluate the metabolic effects of nicotinamide in ovariectomized (OVX) female rats to establish molecular targets against obesity, which support the safe therapeutic application of nicotinamide. The OVX animals were divided into groups: SHAM (simulated surgery), SHAMn (two weeks of 35 mg·kg-1 nicotinamide per day, by gavage), OVX, and OVXn (two weeks of 35 mg·kg-1 nicotinamide per day, by gavage). The results indicated that nicotinamide favored lipolysis, as evidenced by an increase in free fatty acid and hepatic triglyceride levels, which were not fully normalized during the treatment period. The lipolysis appeared to be due to increased SIRT1 and mitochondrial oxidative phosphorylation in muscle and adipose tissue. There were decreases in muscle and fat nicotinamide N-methyltransferase (NNMT), which were associated with decreases in mass and triglyceride, low-density lipoprotein cholesterol (LDLc), and total cholesterol content. Nicotinamide appeared to be beneficial for the glycemic profile, with normal hepatic glycogen storage and a tendency towards insulin sensitivity in the OVXn. In the SHAMn group, nicotinamide led to glucose intolerance, together with reduced muscle expressions of nicotinamide phosphoribosyltransferase (NAMPT) and SIRT3, suggesting that there were no short-term benefits. Supplementation with nicotinamide led to tissue-specific adaptive lipid and molecular changes in OVX rats.

Ovariectomized rodents as a menopausal metabolic syndrome model. A minireview.

Bilateral ovariectomy is the best characterized and the most reported animal model of human menopause. Ovariectomized rodents develop insulin resistance (IR) and visceral obesity, the main risk factors in the pathophysiology of metabolic syndrome (MS). These alterations are a consequence of hypoestrogenic status, which produces an augment of visceral fat, high testosterone levels (hyperandrogenism), as well as inflammation, oxidative stress, and metabolic complications, such as dyslipidemia, hepatic steatosis, and endothelial dysfunction, among others. Clinical trials have reported that menopause per se increases the severity and incidence of MS, and causes the highest mortality due to cardiovascular disease in women. Despite all the evidence, there are no reports that clarify the influence of estrogenic deficiency as a cause of MS. In this review, we provide evidence that ovariectomized rodents can be used as a menopausal metabolic syndrome model for evaluating and discovering new, safe, and effective therapeutic approaches in the treatment of cardiometabolic complications associated to MS during menopause.

Topical capsaicin cream with moderate exercise protects against hepatic steatosis, dyslipidemia and increased blood pressure in hypoestrogenic obese rats.

BACKGROUND: The aim of this study was to evaluate the effects of capsaicin (Cap), moderate exercise (Ex), and their combination on arterial blood pressure (BP) and metabolic complications in hypoestrogenic (HE) obese (HEOb) rats. Female Wistar rats were ovariectomized and given 300 g L-1 sucrose solution (HEOb), or purified water (HE) ad libitum, for 28 weeks. After shaving the abdominal skin, cold cream vehicle was applied to sedentary (Sed) and exercise (Ex) groups, and 0.75 g kg-1 Cap cream was applied to Ex groups. Ex groups ran on a treadmill every day for 20 min at speeds from 0.15 to 0.3 m s-1 . For combination groups (Cap + Ex), topical Cap was applied 90 min before Ex. The treatments were performed for 6 weeks, and BP was recorded before and at the end of the experimental protocol. The animals were killed by decapitation, and blood and tissues were obtained to perform oxidative profile, as well as to undertake biochemical and histologic studies. RESULTS: Compared with individual treatments, the combined therapy (Cap + Ex) in HEOb rats caused a higher reduction in the caloric intake, body weight, abdominal fat percentage, oxidative stress, and hepatic steatosis. In HEOb groups, Cap was the only treatment that reduced BP and prevented dyslipidemia and oxidative stress. CONCLUSION: The present data show that Cap improves the metabolic alterations induced by obesity and hypoestrogenism, suggesting that Cap can be considered as an excellent candidate for therapy of these clinical conditions. © 2020 Society of Chemical Industry.

Reality of premature ovarian failure in Argentina

SUMMARY Premature Ovarian Insufficiency is defined as a decline in ovarian function that is accompanied by two biochemical determinations of Follicle Stimulating Hormone in hypergonadotropic values, in addition to low levels of circulating estrogens in women under 40 years old. Although some of its possible etiologies are recognized and diagnosed, most of the time, its cause remains unknown. It is a pathology with medical, psychological, and reproductive implications. Patients may experience climacteric symptoms, infertility, and emotional distress. In the medium and long term, cardiovascular and bone health can be affected, and some degree of cognitive deterioration can be evidenced. The therapeutic approach needs to be comprehensive for the patient and multidisciplinary. SAEGRE created in Argentina an interhospital network dedicated to gathering relevant statistical information regarding this and other pathologies in order to provide better assistance for these patients.

RESUMO Insuficiência ovariana primária é definida como um declínio da função ovariana acompanhado por dois determinantes bioquímicos do Hormônio Folículo Estimulante em valores hipergonadotróficos, além de baixos níveis de estrogênios circulantes em mulheres com menos de 40 anos de idade. Embora algumas das suas possíveis etiologias serem reconhecidas e diagnosticadas, na maioria das vezes sua causa permanece desconhecida. Trata-se de patologia com a implicações médicas, psicológicas e reprodutivas. Os pacientes podem vivenciar sintomas climatéricos, infertilidade e problemas emocionais. A médio e longo prazo, a saúde cardiovascular e óssea pode ser afetada, e algum grau de deterioração cognitiva pode ser observado. A abordagem terapêutica precisa ser abrangente para o paciente e multidisciplinar. A SAEGRE criou na Argentina uma rede interospitalar dedicada a reunir informações estatísticas relevantes sobre esta e outras patologias, a fim de proporcionar uma melhor assistência para esses pacientes.

Climacteric Symptoms and Sexual Dysfunction: Association between the Blatt-Kupperman Index and the Female Sexual Function Index / Sintomatologia climatérica e disfunção sexual: associação entre o índice de Kupperman e Blatt e o índice de função sexual feminina

Abstract Objective To investigate the association between the intensity of climacteric symptoms and sexual dysfunction in women aged 40 to 65 years. Methods Observational, analytic, cross-sectional study conducted with 63 women aged 40 to 65 treated at the gynecology outpatient clinic of a public hospital in northeastern Brazil. A questionnaire was used to collect identification data, clinical information, gynecological-obstetric data, lifestyle traits and information on chronic diseases. Climacteric symptoms and sexual function were evaluated by means of the Blatt-Kupperman index and the Female Sexual Function Index (FSFI) respectively. The association between the two indices was investigated using the chi-squared test; the difference in mean scores on the FSFI as a function of menopausal status was evaluated by Student's t-test. The significance level was set to p < 0.05. Results The mean value of the Blatt-Kupperman index was 26.42 (standard deviation [SD]: 4.52); 36.51% of the women exhibited severe symptoms. The mean score on the FSFI was 21.84 (SD: 4.11). More than half of the analyzed women (58.73%) exhibited sexual dysfunction (FSFI ≤ 26.5). Regarding the association between the Blatt- Kupperman index and the FSFI, the greater the intensity of the climacteric symptoms (Blatt-Kupperman), the higher the frequency of sexual dysfunction (FSFI). Sexual dysfunction was exhibited by 100% of the participants with severe climacteric symptoms, 70.59% of those with moderate symptoms, and only 9.09% with mild symptoms (p < 0.001). Conclusions The application of the Blatt-Kupperman index and of the FSFI allowed the detection of an association between the severity of climacteric symptoms and the prevalence of sexual dysfunction.

Resumo Objetivo Verificar, em mulheres de 40 a 65 anos, a associação entre a intensidade dos sintomas climatéricos e a disfunção sexual. Métodos Estudo observacional, analítico, transversal, comamostra de 63 mulheres entre 40 e 65 anos atendidas em um ambulatório de ginecologia de um hospital público do Nordeste do Brasil. Foi aplicado um questionário com dados de identificação, informações clínicas, dados ginecológico-obstétricos, hábitos de vida e doenças crônicas. Os sintomas climatéricos e a função sexual foram avaliados utilizando o índice de Kupperman e Blatt e o índice de função sexual feminina (IFSF) respectivamente. Para avaliar a associação entre estes índices, foi utilizado o teste do qui-quadrado, e, para avaliar a diferença entre as médias do IFSF de acordo com o status menopausal, foi utilizado o teste t de Student. Um valor de p < 0,05 foi considerado significante. Resultados A média do índice de Kurpperman e Blatt da população estudada foi de 26,42 (desvio-padrão [DP]: 4,52). Houve presença de sintomas acentuados em 36,51% das mulheres estudadas. A média do IFSF entre as pacientes estudadas foi de 21,84 (DP: 4,11). Mais da metade das mulheres em estudo (58,73%) apresentou disfunção sexual (FSFI ≤ 26,5). Quando analisada a associação entre o índice de Kupperman e Blatt e o IFSF, foi observado que, quanto maior a intensidade dos sintomas climatéricos (Kupperman e Blatt), maior a frequência de disfunção sexual (IFSF). Apresentaram disfunção sexual 100% das pacientes com sintomas climatéricos acentuados, sendo que 70,59% com sintomas moderados, e apenas 9,09% com sintomas leves (p < 0,001). Conclusões No presente estudo, quando aplicados o índicesde Kupperman e Blatt e o IFSF, observou-se associação entre a gravidade dos sintomas climatéricos e a prevalência de disfunção sexual.

Riesgo Cardiovascular en la Anorexia Nerviosa y en otras formas de Amenorrea Hipotalámica Funcional Relacionadas con la Desnutrición / Cardiovascular risk in anorexia nerviosa and other forms of functional hypothalamic amenorrhea related to undernutrition

El disbalance entre el consumo/gasto energético observado en mujeres con amenorrea hipotalámica funcional (AHF) mal nutridas o francamente desnutridas, desencadena una mayor actividad de las hormonas hipotalámicas y neuropéptidos periféricos, destinada a facilitar el aporte de metabolitos energéticos endágenos. La osteoporosis, la inmunodepresión, la amenorrea hipotalámica y el aumento del riesgo cardiovascular (RCV), pueden ser interpretados como efectos secundarios a las reacciones de adaptación homeostática ejercidas por las hormonas centrales y periféricas. El grado de insuficiencia del eje somatotráfico, el hipoestrogenismo y tiempo de evolución, condicionan el tenor de las alteraciones de la circulación coronaria y el compromiso estructural y funcional del miocardio. Un perfil lipídico aterogénico (relación LDL col normal/ HDL col bajo e hipertrigliceridemia) y el ascenso de los marcadores periféricos de procesos inflamatorios y fibrinolíticos, instauran un medio proateroesclerático y protrombático. Frecuentemente es posible observar una prematura presencia de placas de ateroma en las paredes de las carátidas, engrosamiento de su íntima media y la consiguiente rigidez de estas arterias. Ello dificulta la circulación del flujo sanguíneo, induciendo así, la isquemia coronaria y una predisposición al accidente cerebrovascular. Estudios ecocardiográficos exhiben una reducción de la masa muscular de las paredes del ventrículo izquierdo y del septum interventricular. Estos cambios estructurales se correlacionan con una disminución del volumen sanguíneo de la fracción de eyección sistálica postesfuerzo, para presentarse luego en reposo. La alteración del volumen de llenado diastálico puede ser observada si el curso de la enfermedad es relativamente prolongado, evidenciando entonces, un grave compromiso de la performance cardíaca. Si bien, la incidencia de extrasístoles supraventriculares, fibrilación auricular y la bradicardia, no es estadísticamente significativa, la presencia de estas arritmias aumentan el RCV y la posibidad de una eventual muerte súbita.(AU)

The imbalance between energy intake and energy expenditure observed in malnourished or frankly under-nourished women with functional hypothalamic amenorrhea triggers an increased activity of hypothalamic hormones and peripheral neuropeptides, at facilitating the availability of endogenous energy metabolites. Osteoporosis, immune depression, hypothalamic amenorrhea and increased cardiovascular risk can be interpreted as secondary effects of the homeosthatic adaptation reactions by central and peripheral hormones. The extent of somatotropic axis deficiency, hypoestrogenism and time of evolution condition the nature of coronary circulation alterations and myocardial structural and functional involvement. An unfavorable lipid profile (normal LDL/ low HDL and hypertriglyceridemia), the rise in peripheral markers of fibrinolytic and inflammatory processes, results in a proatherosclerotic and prothrombotic environment. A premature presence of atheroma plaques in carotid walls, intima media thickness and subsequent artery stiffness may be frequently observed. This makes blood flow difficult, leading to coronary ischemia and predisposition to stroke. Echocardiographic studies show a decrease in the muscle mass of the left ventricle walls and the interventricular septum. These structural changes correlate with a volume reduction in the post-stress systolic ejection fraction, which subsequently occurs at rest at rest.The reduction in diastolic filling volume can be observed if the course of the disease is relatively long, showing, a serious compromise of cardiac performance. Even if the incidence of supraventricular extrasystoles, atrial fibrillation and bradycardia is not statistically significant, the presence of such arrhythmias increases CVR and the possibility of potential sudden death.(AU)

Riesgo Cardiovascular en la Anorexia Nerviosa y en otras formas de Amenorrea Hipotalámica Funcional Relacionadas con la Desnutrición / Cardiovascular risk in anorexia nerviosa and other forms of functional hypothalamic amenorrhea related to undernutrition

El disbalance entre el consumo/gasto energético observado en mujeres con amenorrea hipotalámica funcional (AHF) mal nutridas o francamente desnutridas, desencadena una mayor actividad de las hormonas hipotalámicas y neuropéptidos periféricos, destinada a facilitar el aporte de metabolitos energéticos endágenos. La osteoporosis, la inmunodepresión, la amenorrea hipotalámica y el aumento del riesgo cardiovascular (RCV), pueden ser interpretados como efectos secundarios a las reacciones de adaptación homeostática ejercidas por las hormonas centrales y periféricas. El grado de insuficiencia del eje somatotráfico, el hipoestrogenismo y tiempo de evolución, condicionan el tenor de las alteraciones de la circulación coronaria y el compromiso estructural y funcional del miocardio. Un perfil lipídico aterogénico (relación LDL col normal/ HDL col bajo e hipertrigliceridemia) y el ascenso de los marcadores periféricos de procesos inflamatorios y fibrinolíticos, instauran un medio proateroesclerático y protrombático. Frecuentemente es posible observar una prematura presencia de placas de ateroma en las paredes de las carátidas, engrosamiento de su íntima media y la consiguiente rigidez de estas arterias. Ello dificulta la circulación del flujo sanguíneo, induciendo así, la isquemia coronaria y una predisposición al accidente cerebrovascular. Estudios ecocardiográficos exhiben una reducción de la masa muscular de las paredes del ventrículo izquierdo y del septum interventricular. Estos cambios estructurales se correlacionan con una disminución del volumen sanguíneo de la fracción de eyección sistálica postesfuerzo, para presentarse luego en reposo. La alteración del volumen de llenado diastálico puede ser observada si el curso de la enfermedad es relativamente prolongado, evidenciando entonces, un grave compromiso de la performance cardíaca. Si bien, la incidencia de extrasístoles supraventriculares, fibrilación auricular y la bradicardia, no es estadísticamente significativa, la presencia de estas arritmias aumentan el RCV y la posibidad de una eventual muerte súbita.

The imbalance between energy intake and energy expenditure observed in malnourished or frankly under-nourished women with functional hypothalamic amenorrhea triggers an increased activity of hypothalamic hormones and peripheral neuropeptides, at facilitating the availability of endogenous energy metabolites. Osteoporosis, immune depression, hypothalamic amenorrhea and increased cardiovascular risk can be interpreted as secondary effects of the homeosthatic adaptation reactions by central and peripheral hormones. The extent of somatotropic axis deficiency, hypoestrogenism and time of evolution condition the nature of coronary circulation alterations and myocardial structural and functional involvement. An unfavorable lipid profile (normal LDL/ low HDL and hypertriglyceridemia), the rise in peripheral markers of fibrinolytic and inflammatory processes, results in a proatherosclerotic and prothrombotic environment. A premature presence of atheroma plaques in carotid walls, intima media thickness and subsequent artery stiffness may be frequently observed. This makes blood flow difficult, leading to coronary ischemia and predisposition to stroke. Echocardiographic studies show a decrease in the muscle mass of the left ventricle walls and the interventricular septum. These structural changes correlate with a volume reduction in the post-stress systolic ejection fraction, which subsequently occurs at rest at rest.The reduction in diastolic filling volume can be observed if the course of the disease is relatively long, showing, a serious compromise of cardiac performance. Even if the incidence of supraventricular extrasystoles, atrial fibrillation and bradycardia is not statistically significant, the presence of such arrhythmias increases CVR and the possibility of potential sudden death.