Pregnancy-associated plasma protein-A is related to gender and to adipocytokine levels: results of the Health Survey of Catalonia.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. AIM: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. DESIGN AND METHODS: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. RESULTS: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) µIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (ß = 0·23; P = 0·02) and leptin (ß = -0·33; P = 0·04). CONCLUSIONS: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined.

Plasma adiponectin distribution in a Mediterranean population and its association with cardiovascular risk factors and metabolic syndrome.

Adiponectin may play an important role in the regulation of body weight, insulin resistance, and cardiovascular disease. The aim of this study was to evaluate the distribution of adiponectin in a Mediterranean adult population and its relationship with cardiovascular risk factors and metabolic syndrome. A cross-sectional study was performed in a representative sample of 1023 subjects from a Spanish Mediterranean population. Individuals with the metabolic syndrome were identified using the diagnostic criteria of the Adult Treatment Panel III. Anthropometric parameters were measured, and biochemical analyses were performed in fasting conditions. Plasma insulin levels were measured and homeostasis model assessment of insulin resistance was calculated. Plasma adiponectin levels were measured by a commercial radioimmunoassay. Median levels of adiponectin were significantly higher in women than in men after adjusting for differences in body mass index. However, no differences in adiponectin plasma levels were observed in relation to age. Significantly lower levels of adiponectin were also observed in women with obesity, abdominal obesity, hyperglycemia or diabetes, low high-density lipoprotein cholesterol, hypertriglyceridemia, or metabolic syndrome. In men, only those with obesity, abdominal obesity, low high-density lipoprotein cholesterol, hypertriglyceridemia, or metabolic syndrome showed significantly lower plasma levels of adiponectin. In a stepwise multivariate analysis, sex, waist circumference, serum C-reactive protein serum levels, and homeostasis model assessment of insulin resistance explained 23.4% of its variability. In conclusion, adiponectin plasma levels are more closely related to the components of the metabolic syndrome in women than in men in a Mediterranean population.

Different patterns of nicotinic acetylcholine receptor subunit transcription in human thymus.

Clinical observations suggest that the thymus is strongly implicated in the pathogenesis of myasthenia gravis (MG), but questions such as the level and location of nicotinic acetylcholine receptor (AChR) subunit expression that are fundamental to postulate any pathogenic mechanism, remain controversial. We have re-examined this question by combining calibrated RT-PCR and real-time PCR to study nicotinic AChR subunit mRNA expression in a panel of normal and myasthenic thymi. The results suggest that the expression of the different AChR subunits follows three distinct patterns: constitutive for, neonatal for gamma and individually variable for alpha1, beta1 and delta. Experiments using confocal laser microdissection suggest that AChR is mainly expressed in the medullary compartment of the thymus but there is not a clear compartmentalization of subunit expression. The different patterns of subunit expression may influence decisively the level of central tolerance to the subunits and explain the focusing of the T cell response to the alpha and gamma subunits.

Pharmacological approaches for the treatment of obesity.

The high incidence of obesity, its multifactorial nature, the complexity and lack of knowledge of the bodyweight control system, and the scarcity of adequate therapeutics have fuelled anti-obesity drug development during a considerable number of years. Irrespective of the efforts invested by researchers and companies, few products have reached a minimum level of effectiveness, and even fewer are available in medical practice. As a consequence of anti-obesity research, our knowledge of the bodyweight control system increased but, despite this, the pharmacological approaches to the treatment of obesity have not resulted yet in effective drugs. This review provides a panoramic of the multiple different approaches developed to obtain workable drugs. These approaches, however, rely in only four main lines of action: control of energy intake, mainly through modification of appetite;control of energy expenditure, essentially through the increase of thermogenesis;control of the availability of substrates to cells and tissues through hormonal and other metabolic factors controlling the fate of the available energy substrates; andcontrol of fat reserves through modulation of lipogenesis and lipolysis in white adipose tissue. A large proportion of current research is centred on neuropeptidic control of appetite, followed by the development of drugs controlling thermogenic mechanisms and analysis of the factors controlling adipocyte growth and fat storage. The adipocyte is also a fundamental source of metabolic signals, signals that can be intercepted, modulated and used to force the brain to adjust the mass of fat with the physiological means available. The large variety of different approaches used in the search for effective anti-obesity drugs show both the deep involvement of researchers on this field and the large amount of resources devoted to this problem by pharmaceutical companies. Future trends in anti-obesity drug research follow closely the approaches outlined; however, the increasing mass of information on the molecular basis of bodyweight control and obesity will in the end prevail in our search for effective and harmless anti-obesity drugs.

[Weight loss in a patient with morbid obesity under treatment with oleoyl-estrone]. / Pérdida de peso en un paciente con obesidad mórbida en tratamiento con oleoil-estrona.

BACKGROUND AND OBJECTIVE: Oleoyl-estrone administration in rats results in loss of body fat and sparing protein via decreasing food intake and maintaining energy expenditure. Oleoyl-estrone also decreases insulin resistance and hyperlipidemia and has no direct estrogenic effects. Our objective was to determine whether oral oleoyl-estrone was effective in the treatment of morbid obesity in a voluntary patient. PATIENT AND METHOD: Oleoyl-estrone (150-300 mol/d) was given to a morbid obese man (BMI: 51.9) over 10 consecutive 21-day trial periods of oral drug intake followed by at least two months of recovery. This treatment was given without additional dietary restrictions. Plasma metabolites, hormones and enzymes were measured before treatment, during active administration and at recovery periods. RESULTS: Oleoyl-estrone decreased the body weight (38.5 kg in 27 months, final BMI: 40.5). No rebound trends were observed. No significant changes in blood parameters, plasma metabolites, hormones or enzymes were observed as a consequence of the treatment. CONCLUSIONS: Oleoyl-estrone decreased body weight in this subject without affecting metabolites or hormones, similarly to its effects in animal models. This means that oleoyl-estrone could have a marked potential as an anti-obesity drug.

Obesity and overweight trends in Catalonia, Spain (1992-2003): gender and socio-economic determinants.

OBJECTIVE: To evaluate the trends of overweight and obesity prevalences in the population of Catalonia, Spain, aged 18-75 years, and the influence of socio-economic determinants on these prevalence trends. DESIGN: Analysis based on data from two representative population-based cross-sectional surveys. SETTING: Data from the two Evaluations of Nutritional Status in Catalonia (ENCAT 1992-93 and ENCAT 2002-03), Spain. Weights and heights were obtained by direct measurement in standardised conditions by trained interviewers. Overweight and obesity were defined using body mass index (BMI) and waist circumference (WC), categorised according to WHO criteria. SUBJECTS: In total, 1015 men and 1233 women from ENCAT 1992-93, and 791 men and 924 women from ENCAT 2002-03. RESULTS: Mean BMI and mean WC were higher in males in 2002-03 as compared to 1992-93, while for females mean BMI was lower except for the youngest group, and mean WC was higher. In men, overall BMI overweight prevalence remained stable (from 44.1% to 43.7%), while obesity increased (from 9.9% to 16.6%); total WC overweight remained stable (from 21.7 to 23.8%), while WC obesity increased (from 13.1% to 24.4%). In women, overall BMI overweight increased (from 29.1% to 30.1%), whereas BMI obesity remained stable (from 15.0% to 15.2%); total WC overweight decreased (from 21.8% to 17.7%), while WC obesity increased (from 24.5% to 31.1%). The socio-economic and education variables had an influence on BMI and WC overweight and obesity rates mainly on females in both surveys and on the youngest men only in the 1992-93 survey. CONCLUSIONS: Ten-year trends indicate that Catalan males are getting bigger overall (BMI) and around the waistline (WC), while Catalan females only have bigger waistlines (WC). BMI male obesity prevalence has overtaken that of females. WC obesity continues to be more prevalent among females than males.