Galectin-3 inhibition prevents adipose tissue remodelling in obesity.

Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg(-1) per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10(-8 )m) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity.

Leptin, a mediator of cardiac damage associated with obesity.

Obesity and excess of adipose tissue are associated with the development of cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia. At the cardiac level, various morphological adaptations in cardiac structure and function occur in obese individuals. Different mechanisms linking obesity to these modifications have been postulated. Adipose tissue and epicardial fat releases a large number of cytokines and bioactive mediators such as leptin. Leptin circulates in proportion to body fat mass, thus serving as a satiety signal and informing central metabolic control centers as to the status of peripheral energy stores. It participates in numerous other functions both peripherally and centrally, as indicated by the wide distribution of leptin and the different isoforms of its receptor in different tissues including the heart. This hormone has distinct effects on the reproductive, cardiovascular, and immune systems; however, its role in the heart could mediate wide physiological effects observed in obese individuals. Oxidative stress is associated with obesity and may be considered to be a unifying mechanism in the development of obesity-related comorbidities. It has been reported that obesity may induce systemic oxidative stress; in turn, oxidative stress is associated with an irregular production of adipokines. We herein review the current knowledge of cardiac effects of leptin and the possible mechanisms that are involved, including oxidative stress that plays a major role in the development of cardiovascular damage.

The potential role of leptin in the vascular remodeling associated with obesity.

BACKGROUND/OBJECTIVES: Extracellular matrix (ECM) participates in the vascular remodeling associated with obesity. We investigated the effects of leptin on the production of ECM components in primary cultured vascular smooth muscle cells (VSMCs) and whether leptin could be a mediator of obesity-induced vascular remodeling. METHODS: T he effects of leptin (100 ng ml(-1)) on ECM components and superoxide anion production (O(2)(.-)) were evaluated in presence or absence of the antioxidant melatonin (10(-)(3) mmol l(-1)) or the inhibitor of phosphatidylinositol 3'-kinase (PI3K), LY294002 (2 × 10(-)(4) mmol l(-1)) in VSMCs from adult rats in order to explore the role of both oxidative stress and the participation of PI3K/Akt pathway in the effects of leptin. ECM components and O(2)(.-) were quantified in the aortic media of male Wistar rats fed a high-fat diet (HFD; 33.5% fat), or a standard diet (CT; 3.5% fat) for 6 weeks. RESULTS: In VSMCs, leptin enhanced gene and protein levels of collagen I, fibronectin, transforming growth factor (TGF)-ß and connective tissue growth factor (CTGF) but did not change those of collagen III and galectin-3. Leptin also increased O(2)(.-) and Akt phosphorylation in VSMCs. These effects were prevented by the presence of either melatonin or LY294002, except O(2)(.-) production in the case of PI3K inhibition. The increase in body weight in HFD rats was accompanied by aorta thickening due to an increase in media area. The aortic fibrosis observed in HFD rats was associated with high levels of leptin, collagen type I, fibronectin, TGF-ß, CTGF, phosphorylated Akt and O(2)(.-). Aortic leptin levels were positively correlated with total collagen, collagen I, TGF-ß and CTGF levels. No differences were observed in the levels of collagen III, elastin or galectin-3 between both the groups. CONCLUSIONS: Leptin could participate in the vascular remodeling and stiffness associated with obesity by ECM production in VSMCs through the activation of oxidative stress-PI3K/Akt pathway and the production of the profibrotic factors TGF-ß and CTGF.

Relevance of vascular peroxisome proliferator-activated receptor γ coactivator-1α to molecular alterations in atherosclerosis.

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is emerging as a novel factor that plays a critical role in integrating signalling pathways in the control of cellular and systemic metabolism. We investigated the role of vascular expression of PGC-1α and related factors, such as sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ (PPARγ) and adiponectin, during the atherosclerotic process. Endothelial function, vascular superoxide anion production and inflammatory mediators were also evaluated. This study was carried out in male New Zealand rabbits fed a diet containing 0.5% cholesterol and 14% coconut oil for 8 weeks. Animals developed mixed dyslipidaemia and atherosclerotic lesions, which were associated with endothelial dysfunction, aortic overproduction of superoxide anions and inflammation. Expression of PGC-1α, SIRT1, PPARγ and adiponectin was reduced (P<0.05) in aorta from atherosclerotic rabbits. Levels of PGC-1α were correlated negatively (P<0.05) with total cholesterol levels, aortic superoxide anion production and tumour necrosis factor-α expression, and positively (P<0.05) with maximal relaxation in response to acetylcholine. The observed results suggest that PGC-1α could be considered to be a link between the main atherosclerotic processes (endothelial dysfunction, oxidation and inflammation) and alterations of other factors involved in vascular wall integrity, such as SIRT1, PPARγ and adiponectin.

Ancient origin of the CTH alelle carrying the c.200C>T (p.T67I) variant in patients with cystathioninuria.

Hereditary cystathioninuria is due to mutations in the CTH gene that encodes for cystathionase, a pyridoxal-5'-phosphate (PLP) dependent enzyme. To date, mutations in this gene have been described in 10 unrelated cystathioninuric patients. Enzyme assays have showed that mutated cystathionase exhibits lower activity than controls. As cystathioninuria is usually accompanied by a wide variety of symptoms, it has been questioned whether it is a disease or just a biochemical finding not associated with the clinical picture of these patients. This is the first report of Spanish patients with cystathioninuria and mild to severe neurological symptoms in childhood. After oral pyridoxine therapy biochemical parameters have normalized but clinical amelioration was not evident. All patients were homozygotes for the c.200C>T (p.T67I) variant which is the most prevalent inactivating mutation in the CTH gene. To further investigate the history of the alleles carrying the c.200C>T transition in Europe, we also constructed the haplotypes on the CTH locus in our Spanish patients as well as in a clinical series of cystathioninuric patients from the Czech Republic harboring the same nucleotide change. We suggest that the CTH p.T67I substitution could have an ancient common origin, which probably occurred in the Neolithic Era and spread throughout Europe.

Metabolic indices shift in the hypothalamic-neurohypophysial system during lactation: implications for interpreting their relationship with neuronal activity.

Metabolic indices of neuronal activity are thought to predict changes in the frequency of action potentials. There are stimuli that do not shift action potential frequency but change the temporal organization of neuronal firing following modifications of excitatory inputs by inhibitory synaptic activation. To our knowledge it is unknown whether this kind of stimulus associates with adjustments of metabolic markers of neuronal activity. Here, we used the hypothalamic-neurohypophysial system of lactating rats to address whether shifts in the temporal organization of neuronal firing relate with modifications of metabolic markers of neuronal activity. Cytochrome oxidase activity, (3)H-2-deoxyglucose uptake, and the area occupied by blood vessels increased in the paraventricular nucleus and neurohypophysis of lactating rats, as compared with their virgin counterparts. Taken together, these results suggest that metabolic demands denote shifts in the temporal organization of action potentials related with the adjustment of excitatory synaptic activation, and support that changes in metabolic markers do not necessarily reflect shifts in the frequency of action potentials.

[Insulin-glucose ratio and body fat composition in patients with chronic anovulation and sterility]. / Relación insulina-glucosa y composición corporal grasa en pacientes con anovulación crónica y esterilidad.

A clinical, descriptive, and transversal study was conducted in a group of patients with chronic anovulation and sterility, to correlate insulin resistance, determined by the fasting glucose/insulin ratio, with body fat composition using anthropometrics parameters and the interaction of light near infrared region method, we studied 41 young patients with chronic anovulation and sterility. Based on their body mass index, all patients had obesity or overweight. Similarly, most of them presented with a percentage of body fat over the recommended limits. Forty percent of all studied patients had a fasting glucose/insulin ratio below 4.5, which corresponds to insulin resistance. The correlation between the percentage of body fat and fasting glucose/insulin ratio was significant, as was the correlation between body mass index and the percentage of body fat. We found overweight or obesity in the majority of our patients, and insulin resistance in almost half of them. Such disturbances were positively associated with the percentage of body fat and android distribution. Therefore, we recommend a routinely anthropometrics evaluation in these patients as well as fasting glucose/insulin ratio determination in order to act in an early stage over the natural history of metabolic syndrome, whose common denominator is insulin resistance.

[Nutritional evaluation and functional class in hospitalized cardiopathy patients]. / Evaluación nutricional y clase funcional del cardiópata hospitalizado.

The nutritional state evaluation of any patient with heart disease must include the anthropometric measures, organic metabolic and cellular immunity test. We evaluated the nutritional state of 75 hospitalized patients with heart disease, and its correlation with New York Heart Association class and heart disease type. There was 36 patients (48%) with normal nutritional state, 24 (32%) with grade I malnutrition, 12 (16%) with grade II malnutrition, and 3 (4%) with grade III malnutrition. Of 23 patients with rheumatic valvular heart disease 83.4% have some degree of malnutrition, 37 patients with ischemic heart disease 25% was under nourished. Fifty percent of patients with hypertensive cardiopathy, 75% of the patients with cardiomyopathy and 83% of the 7 patients with other type of heart disease had some degree of malnourishment. There was a direct correlation between nutritional state and functional class, we found no patient in IV class functional with normal nutritional state, or grade I malnutrition.

Methods of nutritional assessment for determining nutritional care at the pre-school level.

Prevalence of malnutrition in pre-school children may be used to determine the need for nutrition surveillance or nutritional care. That prevalence depends on the nutritional classification used. The authors consider that one of the most recommended classifications used for identifying Protein Energy Malnutrition (PEM) was developed by Waterlow. The criteria includes weight-for-height and height-for-age. Frisancho suggested that Arm Muscle Area (AMA), related to height, could provide useful measurements for assessing mass reserve, thus, in beginning stages of PEM it is worth while to determine those who could benefit from nutritional services. The aim of this study was to determine the percentages of pre-school children considered well nourished by Waterlow indicators, but wasted or below average using the AMA for height criteria. Children (881) of either sex, from 48 to 79 months of age, were studied from the Tijuana, Baja California, Mexico pre-school system. Standard anthropometric measurements were taken including weight, height, upper-arm circumference, and triceps skinfold. Arm muscle area was created from those measurements. Using Waterlow indicators, results showed deficit of height-for-age alone was seen in 25.6%; deficit of weight-for-height alone was observed in 1%; deficit of AMC-for-height, but well nourished by Waterlow indicators was seen in 14.9%. If one speculates that children with deficits of AMC-for-height could have different risks of acquiring a disease compared to those apparently normal, then 14.9% of the studied sample would also need nutritional care. Thus, using these criteria, the need for nutritional surveillance and nutritional education is greater for PEM than that established exclusively using Waterlow criteria.

Methods of nutritional assessment for determining nutritional care at the pre-school level

Prevalence of malnutrition in pre-school children may be used to determine the need for nutrition surveillance or nutritional care. That prevalence depends on the nutritional classification used. The authors consider that one of the most recommended classifications used for identifying Protein Energy Malnutrition (PEM) was developed by Waterlow. The criteria includes weight-for-height and height-for-age. Frisancho suggested that Arm Muscle Area (AMA), related to height, could provide useful measurements for assessing mass reserve, thus, in beginning stages of PEM it is worthwhile to determine those who could benefit from nutritional services. The aim of this study was to determine the percentages of pre-school children considered well nourished by Waterlow indicators, but wasted or below average using the AMA for heigh criteria. Children (881) of either sex, from 48 to 79 months of age, were studied from the Tijuana, Baja California, Mexico pre-school system. Standard anthropometric measurements were taken including wight, height, upper-arm circumference, and triceps skinfold. Arm muscle area was created from those measeurements. Using Waterlow indicators, results showed deficit of heigh-for-age alone was seen in 25.6 per cent; deficit of weight-for-height alone was observed in 1 per cent; deficit of AMC-for-height, but well nourished by Waterlow indicators was seen in 14.9 per cent. If one speculates that children with deficits of AMC-for-height could have different risks of acquiring a disease compared to those apparently normal, then 14.9 per cent of the studied sample would also need nutritional care. Thus, using these criteria, the need for nutritional surveillance and nutritional education is greater for PEM than that established exclusively using Waterlow criteria

[Child abuse: a disturbing problem]. / Maltrato infantil: un problema inquietante.

This current information on "battered child syndrome" (BCS) was obtained during 1990 from nine institutions in Tijuana, Baja California; 549 cases of BCS were studied, of which 338 were female, 203 male, eight of indeterminate sex due to loss documentation. Child abuse was manifested in all its forms: beatings, sexual abuse, neglect, and affective indifference. The victim's and perpetrator's characters were analyzed together with other factors which had to be taken into consideration in order to detect results which were similarly described in the literature. It is of utmost importance to alert all medical staff to this terrible social problem for the complete treatment of the affected child and the family environment. Community support, and legislation to adequately cover rights of minors and their protection are imperative to elimination of the battered child syndrome.

[Fatty and muscular areas of the arm: indicators for the nutritional evaluation of pre-school children]. / Areas grasa y muscular de brazo: indicadores para la evaluación nutricional del preescolar.

The assessment of skinfold thickness has been used to estimate protein reserve through arm muscle area (AMA) and through arm fat area (AFA) it can assess caloric reserve. The aim of this paper is to compare trends of AMA in pre-school children living in Tijuana with american children of the same ages. This study has been accomplish in pre-school children attending to the Federal Education System. Through a randomly sample it was chosen 30 school, afterwards in systematic was done to assess 900 children aged 48 to 78 months old. This studied variables were: weight, height, arm circumference and triceps skinfold thickness, obtained according to accepted techniques at the international literature. From which were created AMA and AFA, according to formulas already described. A multiple regression model was obtained from AMB to height, between expected and experimental values. Using analysis of variance to determined differences between slopes and intercepts. In this paper are shown the statistics and distributions for AMA and AFA. Correlations for reference and experimental values were linear and no significant differences were observed between the slopes and intercepts of the set of data. These results suggest that form the point of view considering AMA, growth rate between Tijuana children and American similars are apparently the same at this ages.