Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women.

Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.

Profile of adipose tissue gene expression in premenopausal and postmenopausal women: site-specific differences.

OBJECTIVES: Menopause increases the risk of several pathologies, probably due to enlarged levels of visceral fat. Apart from morphological and endocrine changes, a cluster of genes, still not fully defined, may be involved in these alterations. The objectives of the present study, therefore, were to analyze differences in adipose tissue gene expression between premenopausal and postmenopausal women and to ascertain whether any differences were depot specific. METHODS: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) biopsies were taken from 7 premenopausal and 7 postmenopausal women undergoing surgery because of morbid obesity. RNA was extracted, and the overall gene expression profile was analyzed by microarray analysis. RESULTS: In general, SAT genes were overexpressed, whereas VAT genes were down-regulated in premenopausal compared with postmenopausal women. We found 724 differentially expressed genes in SAT and 327 in VAT. These differences suggest that several biological processes, such as the immune system and other metabolic processes, were altered based on menopause status. Regarding individual genes, neurexin 3, metallothionein 1E, and keratyn 7 showed the most pronounced differences. Interestingly, the expression of these genes was related to body fat distribution. CONCLUSIONS: Our results reveal that menopause influences the adipose tissue expression of many genes, especially of neurexin 3, metallothionein 1E, and keratyn 7, which are associated with the alteration of several key biological processes, such as the immune system and cell metabolism. Gene expression in adipose tissue could be used for diagnosis and the development of new therapeutic strategies against obesity and related alterations, depending on menopause status.

Relationship of abdominal obesity with cardiovascular disease, diabetes and hyperlipidaemia in Spain.

OBJECTIVES: To evaluate the relevance of obesity and abdominal obesity in the prevalence of cardiovascular disease (CVD), diabetes mellitus, hyperlipidaemia and hypertension in primary care patients and to ascertain whether waist circumference (WC) measurement should be included in routine clinical practice in addition to body mass index (BMI). METHODS: As part of the IDEA study, primary care physicians from Spain recruited patients aged 18-80 years. WC and BMI and the presence of CVD, diabetes mellitus, hyperlipidaemia and hypertension were recorded. Finally, 17 980 were analysed. An age-related increase in adiposity was observed. Overall 33% were obese by BMI, and 51% of subjects presented abdominal obesity by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) (WC > 102 cm for men and > 88 cm for women). Although there was a correlation between BMI and WC, they presented different distribution patterns. Women, but not men, with a high level of education, professional activity and smoking were associated with a lower WC. Abdominal obesity was significantly associated with CVD. Some subjects with abdominal obesity but lean by BMI, showed an increased prevalence of CVD and diabetes. Furthermore, abdominal obesity was strongly associated with dyslipidaemia and hypertension. CONCLUSIONS: Half of the primary care patients studied showed abdominal obesity as measured by WC, whereas one-third was obese by BMI. Abdominal obesity was strongly associated with CVD and diabetes, even in patients lean by BMI. WC should be included in the routine clinical practice in addition to BMI.

[Asymmetric dimethylarginine as cardiovascular risk factor]. / Dimetilarginina asimétrica como marcador de riesgo cardiovascular.

The amino acid L-arginine is the substrate for endothelial nitric oxide synthesis. The endothelium is capable of producing asymmetric dimethylargine (ADMA) (L-arginine methylated). ADMA is able to compete with L-arginine in nitric oxide (NO) production and inhibits oxide nitric synthase activity. Elevated blood levels of ADMA can block the synthesis of NO, and induce endothelial dysfunction, which may lead to the initiation and progression of atherosclerosic vascular disease. Prospective clinical studies in different patients populations suggest that ADMA is a new marker in cardiovascular disease and is to able to predict new cardiovascular events. Recently, intraindividual variations of ADMA in healthy subjects have been described. This fact induces to continue studying the diagnosis and prognosis value of this potential and novel marker of cardiovascular risk.

Dimetilarginina asimétrica como marcador de riesgo cardiovascular / Asymmetric dimethylarginine as cardiovascular risk factor

La dimetilarginina asimétrica (ADMA) es un inhibidor competitivo delgrupo enzimático óxido nítrico (NO) sintetasa, que cataliza la conversióndel aminoácido L-arginina en L-citrulina y NO. Esta competenciase debe a la estrecha similitud entre la composición química de la Largininay la molécula de ADMA (2 grupos metilos en el grupo aminoterminalde la L-arginina). Concentraciones elevadas de ADMA puedenbloquear la síntesis de NO, molécula antiaterógena endógena porexcelencia, debido a su función reguladora del endotelio vascular. Lasdisminuciones del NO favorecen la disfunción endotelial causada porfactores de riesgo cardiovascular, inflamaciones o alteraciones metabólicas.Se han publicado estudios clínicos prospectivos que señalanque la ADMA es un nuevo marcador de riesgo cardiovascular capaz depredecir de forma independiente nuevos eventos. Más recientementese han descrito variaciones intraindividuales de la ADMA en personassanas que inducen a seguir investigando sobre el valor diagnóstico ypronóstico de este potencial y novedoso marcador de riesgo cardiovascular

The amino acid L-arginine is the substrate for endothelial nitric oxidesynthesis. The endothelium is capable of producing asymmetric dimethylargine(ADMA) (L-arginine methylated). ADMA is able to competewith L-arginine in nitric oxide (NO) production and inhibits oxidenitric synthase activity. Elevated blood levels of ADMA can block thesynthesis of NO, and induce endothelial dysfunction, which may leadto the initiation and progression of atherosclerosic vascular disease.Prospective clinical studies in different patients populations suggestthat ADMA is a new marker in cardiovascular disease and is to able topredict new cardiovascular events. Recently, intraindividual variationsof ADMA in healthy subjects have been described. This fact inducesto continue studying the diagnosis and prognosis value of this potentialand novel marker of cardiovascular risk

Prevention of overweight and obesity: a Spanish approach.

BACKGROUND: Obesity is considered a major public health issue in most developed countries nowadays. This paper provides an overview of current population data available in Spain and the approach to develop preventive strategies in the country. METHODS: Review of population data available is based on individually measured weight and height as well as determinants. On this basis, the approach used in the country to develop preventive strategies is discussed. RESULTS: According to the DORICA study, the prevalence of obesity (BMI >or=30 kg m-2) is 15.5% in Spanish adults aged 25-60 years (13.2% in men and 17.5% in women). Obesity rates are higher among women aged 45 years and older, low social class, living in semi-urban places. Population estimates for the prevalence of obesity in Spanish children and young people based on the enKid study are 13.9% for the whole group. In this study, overweight and obesity is related to absence of breastfeeding, low consumption of fruit and vegetables, high consumption of cakes, buns, softdrinks and butchery products, low physical activity levels and a positive association with time spent watching TV. In 2005, the Spanish Ministry of Health jointly with the Spanish Agency for Food Safety and Nutrition launched the multifaceted NAOS strategy for nutrition, physical activity and the prevention of obesity. The important role of the family and the school setting as well as the responsibility of the Health Administration and Pediatric Care in the prevention of obesity is highlighted in the document. The need for environmental actions is recognised. The PERSEO programme, a multicomponent school-based intervention project is part of the strategy currently in place. CONCLUSION: Obesity is a public health issue in Spain. A national multifaceted strategy was launched to counteract the problem. Environmental and policy actions are a priority. Young children and their families are among the main target groups.

[New therapeutic aspects for the control of risk factors in obesity]. / Nuevos aspectos terapéuticos para el control de los factores de riesgo de la obesidad.

Treatment of obesity continues to rely upon the classical triad of nutritional advise, increase of physical activity and use of drugs. However, in recent years, there have appeared novelties in both therapeutic targets and new molecules. With regard to therapeutic targets of obesity, success does not consist of losing much weight but attaining a moderate yet maintained weight lose (5-10% of initial weight) at the expense of visceral fat. In other words, instead of weight, what is needed is a waist reduction, mainly to improve or prevent obesity-related metabolic and vascular complications. Regarding drugs, a new molecules is about to appear in the international pharmaceutical market: rimonabant. A selective blocker of the endocannabinoid receptor CB1, it has proven to be effective and safe in treating obesity and its comorbidities. Another known agent, orlistat, has proven to be effective in the prevention of the development of type 2 diabetes in obese patients with or without glucose intolerance.

Increased exercise capacity after surgically induced weight loss in morbid obesity.

OBJECTIVE: To investigate the effects of surgically induced weight loss on exercise capacity in patients with morbid obesity (MO). RESEARCH METHODS AND PROCEDURES: A prospective 1-year follow-up study was carried out, with patients being their own controls. A symptom-limited cardiopulmonary exercise stress test was performed in 31 MO patients (BMI > 40 kg/m2) before and 1 year after undergoing bariatric surgery. RESULTS: At 1 year after surgery, weight was reduced from 146 +/- 33 to 95 +/- 19 kg (p < 0.001), and BMI went from 51 +/- 4 to 33 +/- 6 kg/m2 (p < 0.001). After weight loss, obese patients performed each workload with lower oxygen consumption, heart rate, systolic arterial pressure, and ventilatory volume (p < 0.001). This reduced energy expenditure allowed them to increase the duration of their effort test from 13.8 +/- 3.8 to 21 +/- 4.2 minutes (p < 0.001). Upon finishing the exercise, MO patients before surgery were able to reach only 83% of their age-predicted maximal heart rate, and their respiratory exchange ratio was 0.87 +/- 0.06. After weight loss, those values were 90% and 1 +/- 0.08, respectively (p < 0.01). When we compared the peak O2 pulse corrected by fat free mass before and after surgery, no significant differences between the groups were found. DISCUSSION: After surgically induced weight loss, MO patients markedly improved their exercise capacity. This is due to the fact that they were able to perform the external work with lower energy expenditure and also to increase cardiovascular stress, optimizing the use of cardiac reserve. There were no differences in cardiac function before and after surgery.

Obesity: epidemiology and clinical aspects.

At the beginning of the 21st Century, obesity has become the leading metabolic disease in the World. So much so, that the World Health Organisation refers to obesity as the global epidemic. In fact, obesity is a common disease affecting not only affluent societies but also developing countries. Currently 300 million people can be considered as obese and, due to the rising trend in obesity prevalence, this figure could double by year 2025 if no action is taken against this threat. In terms of health impairment, the importance of obesity lies in the fact that, besides being a disease in itself, it is a risk for many other diseases, mainly from the metabolic and cardiovascular area. Among these, type 2 diabetes, dyslipemia, hyperuricemia, arterial hypertension and cardiovascular disease are the most frequent. Also, respiratory diseases such as obesity hypoventilation syndrome and obstructive sleep apnoea syndrome are strongly associated with obesity.

[Cardiopulmonary function and exercise capacity in patients with morbid obesity]. / Función cardiopulmonar y capacidad de ejercicio en pacientes con obesidad mórbida.

INTRODUCTION AND OBJECTIVES: The effect of obesity on cardiac function is still under discussion. The objective of this study was to assess cardiopulmonary capacity in morbidly obese patients. Patients and method. A symptom-limited cardiopulmonary exercise stress test was carried out in 31 morbidly obese patients (BMI 50 9 kg/m2) and 30 normal controls (BMI 24 2 kg/m2. Cardiovascular function was evaluated using the oxygen pulse (oxygen uptake/heart rate). RESULTS: There were no differences in age, sex and height between both groups. During the effort the obese subjects presented greater oxygen uptake, heart rate, systolic arterial pressure and minute ventilation and shorter test duration than control group (14 3 vs 27 4 min; p < 0.001). Oxygen pulse values were higher in obese patients. However, after oxygen uptake indexation by fat free mass, these differences disappeared, suggesting a similar cardiovascular function. At the end of the exercise, the control group reached 96% of their age-predicted maximal heart rate and their respiratory exchange ratio was 1 0.2. Obese patients only reached 86% and 0.87 0.2, respectively. CONCLUSIONS: Due to their need of more energy output to move total body mass morbidly obese patients have a reduced exercise capacity. They finish the test having done a submaximal exercise. However, during this effort they show a normal cardiopulmonar capacity.

Función cardiopulmonar y capacidad de ejercicio en pacientes con obesidad mórbida / Cardiopulmonary function and exercise capacity in patients with morbid obesity

Introducción y objetivos. La repercusión de la obesidad sobre la función cardíaca es motivo de controversia. El propósito del presente estudio ha sido determinar la capacidad cardiopulmonar en pacientes con obesidad mórbida. Pacientes y método. Hemos realizado una ergoespirometría limitada por síntomas a 31 pacientes con obesidad mórbida (IMC 50 ñ 9 kg/m2) y a 30 individuos como grupo control (IMC 24 ñ 2 kg/m2). La función cardiovascular ha sido valorada mediante el pulso de oxígeno (consumo de oxígeno/frecuencia cardíaca).Resultados. No existían diferencias en edad, sexo y talla entre ambos grupos. Durante el esfuerzo, los sujetos obesos presentaron un consumo de oxígeno, frecuencia cardíaca, presión arterial sistólica y ventilación por minuto significativamente más elevados que el grupo control, con menor duración de la prueba (14 ñ 3 frente a 27 ñ 4 min; p < 0,001). Los valores de pulso de oxígeno fueron más altos en los pacientes obesos. Sin embargo, tras corregir el consumo de oxígeno por la masa magra, las diferencias en el pulso de O2 desaparecieron, demostrando una función cardiovascular similar. Al final del ejercicio, el grupo control alcanzó el 96 por ciento de su frecuencia cardíaca máxima teórica y su cociente respiratorio fue de 1 ñ 0,2. Los pacientes obesos sólo alcanzaron el 86 por ciento de la frecuencia cardíaca máxima teórica y su cociente respiratorio fue de 0,87 ñ 0,2.Conclusiones. Los pacientes con obesidad mórbida tienen una capacidad de trabajo reducida debido al gran consumo energético que realizan al mover su masa corporal. Finalizan la prueba habiendo realizado un esfuerzo submáximo. No obstante, durante este esfuerzo demuestran una capacidad cardiopulmonar normal (AU)

[The CARMEN trial: increased intake of carbohydrates--simple or complex--and unchanged blood lipids in overweight subjects]. / CARMEN-studiet. Øget indtagelse af kulhydrater--simple eller komplekse--og nedsat fedtindtagelse giver moderat vaegttab og uaendrede blodlipider hos overvaegtige.

INTRODUCTION: The purpose was to investigate the long-term effect of ad libitum low-fat, high-carbohydrate diets with mainly simple or complex carbohydrates on body weight and blood lipids. MATERIAL AND METHODS: A six-months controlled randomised multicentre trial with the participation of five European centres. A total of 398 moderately obese subjects (BMI: 30.4 +/- 2.7 kg/m2, mean +/- SD) were randomised to four groups: Control diet group with normal macronutrient intake, a low-fat/high simple carbohydrate group, a low-fat/high complex carbohydrate group and a seasonal control group. RESULTS: After six months we found a drop in body weight of 1.7 kg (p < 0.05) in the simple and of 2.6 kg (p < 0.001) in the complex carbohydrate group compared with the control diet group. Fat mass decreased by 1.9 kg (p < 0.05) and 2.4 kg (p < 0.001) in the simple and complex carbohydrate group, respectively, compared with the control diet group. There were no significant changes or group differences in fasting blood lipids, glucose, insulin, or leptin. DISCUSSION: The results show that it is favourable to replace dietary fat by carbohydrates (simple or complex) in relation to body weight regulation. No detrimental effects were seen on blood lipids in contrast to previous contentions. Our results underline the importance of a low-fat/high-carbohydrate diet in the management of obesity and the ensuing health problems.

Alteraciones hormonales en mujeres jóvenes con obesidad mórbida / Hormonal alterations on young morbid obese women

FUNDAMENTO: La obesidad humana es una enfermedad de amplia distribución que presenta una considerable variabilidad en su gravedad, manifestaciones metabólicas y endocrinas y etiología. En el presente estudio hemos determinado si en mujeres adultas jóvenes la obesidad mórbida sin complicaciones afecta con diferente intensidad los valores circulantes de hormonas que se ha postulado que intervienen en el desarrollo y mantenimiento de la obesidad. SUJETOS Y MÉTODO: Se estudiaron y determinaron los valores circulantes medios (desviación estándar [DE]) de las hormonas y proteínas relacionadas con el control del peso corporal en 20 mujeres obesas mórbidas (índice de masa corporal, 52,6 [8,3] kg/m2) y 10 controles de peso normal (índice de masa corporal 19,9 [2,1] kg/m2) de edades similares. RESULTADOS: En las mujeres obesas se evidenciaron concentraciones más altas de insulina y leptina, y más bajas de cortisol y de la globulina que se une al cortisol (CBG). No se apreciaron diferencias para la tiroxina libre, hormona estimuladora del tiroides, estrona libre, acilestrona y sulfato de deshidroepiandrosterona. CONCLUSIONES: Los resultados indican que la obesidad mórbida implica la alteración de los principales sistemas hormonales que controlan la disponibilidad de energía y la respuesta a los retos externos, con la notable excepción del tiroides. Hay claras alteraciones en la insulina y leptina mientras que los cambios en el cortisol pueden estar correlacionados con factores distintos a la obesidad. Los valores de acilestrona menores de lo esperado apuntan a un posible déficit de esta señal de ponderostato en las mujeres obesas. La edad relativamente joven de las mujeres del estudio puede ayudar a explicar la relativa suavidad de los cambios hormonales observados (AU)