Biomedical subjects

A Marti

Publications and source records attributed to A Marti.

At least 19 recordsLinked to original sources

PubMed2006

Effects of eicosapentaenoic acid (EPA) on adiponectin gene expression and secretion in primary cultured rat adipocytes.

Adiponectin, a hormone produced by adipocytes, is involved in glucose metabolism and insulin sensitivity. The production of this adipokine is impaired in obesity and insulin resistance. Eicosapentaenoic acid (EPA) is a dietary n-3 polyunsaturated fatty acid that improves insulin sensitivity in several models of obesity and diabetes, which has been suggested to be related to adiponectin induction. An increase in adiponectin production has been also associated with an up-regulation of the transcriptional factor PPARgamma. The aim of this trial was to evaluate the direct effects of EPA on adiponectin gene expression and protein secretion in isolated rat adipocytes as well as to explore the potential mechanisms involved. A comparative study with troglitazone, a PPARgamma agonist, was also performed. For these purposes, primary rat adipocytes were cultured with EPA (100 and 200 microM) and with troglitazone (10 microM) for 96 hours. Both EPA and troglitazone improved glucose utilization by adipocytes. As expected, troglitazone enhanced adiponectin secretion and increased PPARgamma gene expression. However, EPA significantly decreased adiponectin gene expression and protein secretion and reduced PPARy mRNA levels, suggesting that the inhibition of adiponectin by EPA is likely to be secondary to the down-regulation of this adipogenic transcription factor. Moreover, these results suggest that other mechanisms different from the direct stimulation of adiponectin by the fatty acid are underlying the insulin-sensitizing properties observed after EPA treatment in vivo.

Adipocytes↗

PubMed2006

An open pharmacokinetic study of hexylaminolevulinate-induced photodiagnosis after intravesical administration.

BACKGROUND AND OBJECTIVES: Hexylaminolevulinate-mediated photodiagnosis of superficial bladder cancer recently gained marketing authorisation in Europe and is therefore being used increasingly, especially to visualise flat tumours such as carcinoma in situ. Although no significant adverse effects related to the drug have been reported to date, precise information with respect to the safety of this procedure in clinical practice has not yet been published. In the present study, we investigated the possible systemic absorption of different hexylaminolevulinate concentrations and characterised the adverse effects after bladder instillation. METHODS: Twelve patients with known bladder cancer received a 2-hour administration of 50 mL of phosphate-buffered saline containing 4 mmol/L, 8 mmol/L or 16 mmol/L of hexylaminolevulinate. Safety was primarily evaluated by monitoring adverse effects. Standard haematology and clinical biochemistry were assessed by the local hospital laboratory. Measurements of hexylaminolevulinate, 5-aminolevulinate and protoporphyrin IX in plasma and solution collected after instillation were performed, as were fluorescence measurements in the urothelium and the skin by using an optical fibre-based spectrofluorometer. RESULTS: No hexylaminolevulinate was found in the plasma. Furthermore, 5-aminolevulinate and protoporphyrin IX showed no significant increases in plasma after intravesical instillation of hexylaminolevulinate 4 mmol/L, 8 mmol/L or 16 mmol/L for 2 hours. This implies a very low systemic absorption at the administered doses with a hexylaminolevulinate uptake from the bladder of about 5%. Neither skin sensitivity nor adverse reactions that could be attributed to the drug were reported. Renal and liver function were not affected by the hexylaminolevulinate doses used in this study. CONCLUSION: We demonstrated for the first time that hexylaminolevulinate-mediated photodiagnosis is a safe procedure for a patient undergoing this examination, the drug being only minimally systemically absorbed after intravesical instillation. Therefore, no or only minimal adverse effects compared with those seen with conventional photosensitising agents can be expected.

Administration, Intravesical↗

PubMed2005

Serum and gene expression levels of leptin and adiponectin in rats susceptible or resistant to diet-induced obesity.

The aim of the present study was to identify the role of leptin and adiponectin in the development of resistance or susceptibility to diet-induced obesity in rats. For this purpose, male Wistar rats were fed with standard laboratory diet (control group) or cafeteria diet. After 15 days, two groups of rats with different response respect to the cafeteria diet were identified, and were assigned as diet-induced obesity (DIO) and diet resistant (DR) rats. The high-fat diet induced a very significant increase in both body and fat mass weight in DIO group. However, DR rats, gained even less weight than control-fed animals. Food intake was increased in cafeteria-fed rats (both DIO and DR) in comparison to control group; but hyperphagia was higher in DIO rats. In addition, feed efficiency (the ratio of weight gained to calories consumed) was significantly decreased in DR as compared to DIO rats. Regarding leptin, a significant increase in both adipose tissue gene expression and serum levels was observed in DIO rats in comparison with other groups (control and DR). A significant increase in both adiponectin circulating levels and adipose tissue mRNA expression was also observed in DIO animals as compared with the other groups. These data suggest that the susceptibility to obesity of DIO rats might be secondary, at least in part, to an earlier development of leptin resistance, which could lead to alterations in food intake (hyperphagia) and energetic metabolism. However, neither changes in leptin or adiponectin seem to be involved in the adaptive mechanisms that confer resistance to high fat intake.

Adipose Tissue↗

PubMed2005

Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health.

Data from a number of studies and trials have shown that different conjugated linoleic acids (CLA's) may produce beneficial effects on cancer, atherosclerosis, hypertension, diabetes and changes in body composition. Despite the increasing knowledge about CLA's implications on health, the mechanism of action of these fatty acids is not completely understood. Moreover, human studies indicate that some of these beneficial effects are considerably less evident than anticipated from mice studies, while the efficacy and safety of dietary supplements containing CLA have been questioned in some intervention trials. Recently, it has been suggested that the anti-carcinogenic and anti-atherosclerosis effects of CLA's stem from its anti-inflammatory properties. Because inflammatory responses are associated with the pathophysiology of many diseases, including obesity and the metabolic syndrome, the investigation in this area is of growing interest in recent years.

Anti-Inflammatory Agents↗

PubMed2005

High-fat feeding period affects gene expression in rat white adipose tissue.

The expression of 76 sequences, previously isolated as differentially expressed in visceral white adipose tissue (WAT) of female rats, fed with a high-fat diet for 11 days (Lopez et al., Biochem Biophys Res Comm 318: 234-239, 2004), was analyzed in epidydimal WAT of male rats after a feeding period of 65 days with the same diet, using microarray technology. After Northern blot validation of the results, only three genes appeared upregulated (caveolin-2, the alpha-1 chain of haemoglobin and rat mammary tumor-7) and two downregulated (adiponectin and dystroglycan). We have also analyzed caveolin-1 gene expression and found that follows the opposite pattern of caveolin-2, indicating that they are inversely regulated. Our results suggest that if feeding with a high-fat diet is prolonged, many of the initial changes in gene expression, probably aimed to consume the energy surplus and prevent excessive fat deposition, are not maintained, and adaptation to an increased lipid storage is developed.

Adiponectin↗

PubMed2005

No evidence of association between the serotonin 2A receptor--1438G/A promoter polymorphism and childhood obesity in a Spanish population: A case-parent study and a matched case-control study.

Serotonin has been related to feeding behaviour and body weight control through its suppressive effect on appetite. Conflicting results have been published in the literature regarding the association between the - 1438 G/A promoter polymorphism of the 5HT2A gene with obesity-related variables. The aim of this study was to assess the association between the--1438 G/A polymorphism of the 5HT2A gene with childhood obesity in a Spanish population. A total of 136 cases aged 6-16 years with BMI above the 97th percentile of the Spanish BMI reference data for age and gender were matched by gender and age (+/- 6 months) with 136 controls. Additionally, 43 obese children and their parents were selected for a family-based association study (case-parent study). Genotyping was carried out by polymerase chain reaction and restriction enzyme analysis. Conditional logistic regression and transmission/disequilibrium test were used to assess genotype-obesity association. In the matched case-control study, the crude and adjusted odds ratios for the association between 5HT2A--1438 G/A genotypes were nonsignificant. Likewise, no association is suggested by the case-parent study. In conclusion, it is unlikely that the--1438 G/A polymorphism of 5HT2A gene may influence obesity in a Spanish children population.

Alleles↗

PubMed2005

Does weight loss prognosis depend on genetic make-up?

The prevalence of obesity is rising throughout the world. Indeed, obesity has reached epidemic proportions in many developed and transition countries. Obesity is a complex disease with multifactorial origin, which in many cases appears as a polygenic condition affected by environmental factors. Treatment or prevention of obesity is necessary to reverse or avoid the onset of type 2 diabetes and other obesity-related diseases. Weight loss is a complex trait that depends on many environmental, behavioural and genetic influences. An effective programme for the management of overweight and obesity must take into account all of these factors. Individual responses to weight loss interventions vary widely and reliable predictors of successful slimming are poorly understood. The individual genetic make-up participating in energy expenditure regulation, appetite control, lipid metabolism and adipogenesis, have been reported to affect the risk of treatment failure in some subjects. In addition, the genotype could also help to predict the changes in lipid profile, cardiovascular risk factors and insulin sensitivity in response to weight loss. Herein, the current evidence from human studies that support the existence of a genetic component and the participation of different polymorphisms in the prognosis of weight loss induced by interventions leading to a negative energy balance are reviewed.

Energy Metabolism↗

PubMed2004

Decreased splenic mRNA expression levels of TNF-alpha and IL-6 in diet-induced obese animals.

Obesity could be considered as a systemic low-grade inflammatory condition affecting inflammation markers. Adipose tissue synthesizes cytokines whose degree of elevation may depend on the obesity status. Recently, new information is collected on the cross-talking between immune system and adipose tissue in obesity. We report hereby that tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) gene expression in spleen of diet-induced obese animals were markedly decreased (more than 50%) as a consequence of the high fat feeding during five weeks. Interestingly, a very significant negative correlation was found between splenic TNF-alpha mRNA levels and total fat pads (r = -0.806, p = 0.000). These findings support the hypothesis that TNF-alpha gene expression may follow different trends in obese animals adipocytes and splenocytes.

Adipose Tissue↗

PubMed2004

Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents.

AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene to obesity risk in a Spanish children and adolescent population. METHODS: We designed a sex- and age-matched case-control study. Participants were 185 obese and 185 control children (aged 5-18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPAR gamma 2 mutation and BstNI for ADR beta 3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls. RESULTS: Carriers of the polymorphism Pro12Ala of the PPAR gamma 2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09-4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17-5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPAR gamma 2 and ADR beta 3) was 5.30 (95% CI=1.08-25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43-146.8). CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene for obesity risk was found in a case-control study including children and adolescents.

Adolescent↗

PubMed2004

Genes, lifestyles and obesity.

OBJECTIVE: To review the role of genes and lifestyle factors, particularly dietary habits and physical activity patterns, in obesity risk as well as their potential interactions. DESIGN AND MEASUREMENTS: A descriptive report of a number of genes definitely ascribed or potentially implicated in excessive fat accumulation leading to obesity as assessed by different research approaches (Mendelian transmission, genetic animal models, epidemiological association/linkage studies and genome-wide scans). Also, the involvement of macronutrient intake and composition (fat/carbohydrate) as well as the role of activity-linked energy expenditure in obesity onset is reviewed. RESULTS: Examples of the role of the genotype as well as of the dietary macronutrient composition/intake and sedentary/low energy cost of physical activities in obesity prevalence are reported. CONCLUSIONS: Both genes and everyday life environmental factors such as cultural and social mediated food intake and reduced domestic and living work activities are involved in the obesity pandemia. The occurrence of gene x gene and gene x environmental factors interactions makes it more difficult to interpret the specific roles of genetics and lifestyle in obesity risk.

Diet↗

PubMed2004

Less invasive stabilization of complex tibial plateau fractures: a biomechanical evaluation of a unilateral locked screw plate and double plating.

OBJECTIVE: To compare the vertical subsidence in a bicondylar tibial plateau fracture model stabilized either by a unilateral locked screw plate (LSP) or by double plating. DESIGN: Biomechanical cadaver study. INTERVENTION: A 41-C1 fracture model was created in eight pairs of fresh-frozen human cadaver tibiae. Stabilization was performed either by open reduction and internal fixation (ORIF) using a lateral L-buttress plate and a medial four-hole, one-third tubular antiglide-plate or by a lateral LSP. Four load levels (400N, 800N, 1200N, 1600N), each with five cycles, were consecutively applied to the medial plateau. MAIN OUTCOME MEASUREMENTS: The vertical plastic deformation at the end of each cycle was the main parameter of interest. Statistical analysis was performed with the two-way ANOVA test for repeated measurements. Each individual loading level was analyzed separately using Student t test. RESULTS: In one pair, both fixation techniques failed at the first loading cycle of 1200N. One ORIF fixation failed at the first loading cycle of 1600N. The average plastic vertical subsidence was 0.40 mm (LSP) and 0.25 mm (ORIF) at 400N (P = 0.291), 0.83 mm (LSP) and 0.81 mm (ORIF) at 800N (P = 8.82), 1.06 mm (LSP) and 0.96 mm (ORIF) at 1200N (P = 0.98), and 1.54 mm (LSP) and 1.14 mm (ORIF) at 1600N (P = 0.53). Vertical subsidence depended on the applied load (P = 0.002), but not on the method of fixation (P = 0.236). CONCLUSION: Both fixation techniques have a high resistance to vertical subsidence even with loads exceeding the average body weight. No statistically significant difference was seen between the two methods of fixation.

Aged↗

PubMed2004

Influence of two polymorphisms of the tumoral necrosis factor-alpha gene on the obesity phenotype.

Several populational-based studies have suggested an association between tumoral necrosis factor-alpha (TNF-alpha) polymorphisms and obesity-related phenotypes. Therefore, this study aimed at assessing the situation (frequency and associated phenotype) of two TNF-alpha common polymorphisms in a Spanish population. In a case-control design study, a group of Spanish subjects (n=313) were genotyped for the TNF-alpha G/A -308 and -238 polymorphisms. Obese subjects (cases) were compared with lean individuals (controls) according to body mass index (BMI; cases: BMI >30 kg/m2, controls: BMI <25 kg/m2). Waist-to-hip ratio, body composition and some metabolic indicators were assessed. The frequency of the -308A allele (0.14) and -238A allele (0.09) was similar to those previously reported in other Caucasian populations. Interestingly, cases with the -308A allele of the TNF-alpha gene have significantly higher hip and waist circumferences (p<0.05), BMI (p<0.01) and body fat mass (p<0.05) values than obese individuals carrying the -308G allele, but not the waist-to-hip ratio. No apparent influence of the -308A polymorphism on other metabolic indicators (insulin and leptin levels) was found. We could not detect any association between the substitution at position -238 polymorphism of the TNF-alpha gene and obesity anthropometrical phenotypes in this Spanish population, despite some differences in plasma leptin. These results support the hypothesis that the G/A -308 polymorphism of the TNF-alpha gene is associated with a higher BMI as well as hip ad waist circumferences, particularly on female bearers, while no influence on such measurements was found for the G/A -238 TNF-alpha gene polymorphism, but only an effect on leptinaemia.

Adult↗

PubMed2003

NF-kappa B-binding activity in an animal diet-induced overweightness model and the impact of subsequent energy restriction.

An impaired immune function linked to obesity has been shown in both human and animal studies. The purpose of this work was to analyse the hypothesis that PPAR gamma 1 participates in the inhibition of the immune response by affecting the DNA-binding ability of the NF-kappa B complex and whether the SREBP-1 expression can regulate PPAR gamma 1 expression in spleen. Diet-induced overweight rats showed higher PPAR gamma 1 (p<0.05) and lower SREBP-1 (p<0.01) mRNA expression levels with an inhibition of the DNA-binding ability of NF-kappa B compared to control rats as determined by gel-shift analysis. On the other hand, energy restriction decreased SREBP-1 (p<0.01) mRNA expression with no differences in PPAR gamma 1 mRNA expression compared to non-restricted rats, which was accompanied by a restoration in the DNA-binding ability of NF-kappa B as shown by gel-shift analysis. These results suggest that PPAR gamma 1 may be involved in the altered immune response through changes in the activity of NF-kappa B.

Animals↗

PubMed2003

Effects of a beta3-adrenergic agonist on the immune response in diet-induced (cafeteria) obese animals.

Molecules with affinity for beta3-adrenoceptors are not only effective anti-obesity agents in rodent models, but may play a role in the regulation of the immune response. The aim of the current investigation was to analyse the effects of trecadrine on the immune response in diet-induced (cafeteria) obese rats. Male Wistar rats were divided into 2 groups, the control group (C, n=9) was fed with the standard pelleted chow laboratory diet, while the other group was fed with a high-fat (cafeteria) diet. Cafeteria-fed rats were divided into two new subgroups (n=9 each), which received either i.p. saline (obese, O) or trecadrine (1mg/kg/day) (obese+trecadrine, O+T) daily for 5 weeks. Lymphocyte subpopulations and the proliferative response were determined by validated procedures. The administration of trecadrine was able to prevent the onset of obesity in cafeteria-fed rats. Trecadrine-treatment to obese animals appeared to improve the number of lymphocyte subpopulations (CD4+ and CD8+) as compared to those animals only receiving the high-fat diet, being the values of the trecadrine-treated animals on the high-fat diet similar to the control rats. However, the lymphoproliferative response when stimulated with several mitogens was markedly reduced by the cafeteria intake and was further decreased by the beta3-adrenergic administration. The spleen mRNA expression level of UCP2, PPARgamma and Ob-Rb were not affected by the trecadrine treatment. Summing up, at the immune system level, trecadrine administration increased the proportion of CD4+ spleen lymphocytes, although it was not able to restore the lymphocyte proliferative response which was depressed.

Adipose Tissue↗

PubMed2003

Effects of arachidonic acid on leptin secretion and expression in primary cultured rat adipocytes.

Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. Several studies have suggested that leptin can be regulated by macronutrients intake. Arachidonic acid is a dietary fatty acid known to affect cell metabolism. Controversial effects of this fatty acid on leptin have been reported. The aim of this experimental trial was to evaluate the effect of the arachidonic acid on basal and insulin-stimulated leptin secretion and expression in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of the arachidonic acid on indices of adipocyte metabolism were also examined. Isolated adipocytes were incubated with arachidonic acid (1-200 microM) in the absence and presence of insulin (1.6 nM). Leptin secretion and expression, glucose utilization and lactate production were determined at 96 h. The arachidonic acid (200 microM) inhibited both the basal and insulin stimulated leptin secretion and expression. Glucose utilization was not affected by the acid. Basal lactate production was increased by the fatty acid at the highest concentration used (200 microM), however lactate production in presence of insulin was not modified. Finally, the percentage of glucose carbon released as lactate was significantly increased (200 microM). These results suggest that the inhibitory effect of the arachidonic acid on leptin secretion and expression may be due, al least in part, to the increase in the anaerobic utilization of glucose.

Adipocytes↗

PubMed2003

LISS PLT: design, mechanical and biomechanical characteristics.

Following the development of the Less Invasive Sabilization System for Distal Femur a similar system for proximal tibia fractures (LISS PLT) was designed. Anatomical studies were carried out to define the shape of the plate and the position and orientation of the screws. Standard mechanical tests were performed to ensure that the LISS PLT fixation provides similar fatigue resistance to that of conventional plates. Finally, cadaver tibia pairs were used to compare the biomechanical performance of the new device to that of bilateral plating. An unstable intra-articular proximal tibia fracture model was used. The medial condyle of the tibias were submitted to loading cycles with increasing load levels and the vertical subsidence of the medial condyle during the loading cycles was monitored. Comparable stability against secondary loss of reduction was observed for the LISS PLT and the bilateral plating constructs.

Biomechanical Phenomena↗

PubMed2003

Basal fat oxidation and after a peak oxygen consumption test in obese women with a beta2 adrenoceptor gene polymorphism.

The Glu27Glu genotype in the beta2-adrenergic receptor (ADRB2) has been linked to a higher fat deposition and obesity in females. Also, in our population, it has been described that physically active women carrying the Glu allele had a higher BMI as compared to non-carriers performing the same level of activity. Since exercise may counterbalance a gene predisposition to obesity, we tested the hypothesis of a potential different metabolic response among ADRB2 Gln27Gln versus Glu27Glu obese women when submitted to a peak oxygen consumption test on a treadmill. In our study, 10 obese women with the Gln27Gln genotype were compared to 9 matched obese women bearing the Glu27Glu genotype. The ADRB2 polymorphism was identified by PCR-RFLP, fat oxidation was determined by indirect calorimetry and blood measurements were carried out following conventional procedures. The ADRB2 Glu27Glu subjects had lower plasma glycerol levels (P = 0.026), while plasma triglycerides (P <0.001) and the insulin:glucose ratio were higher (P = 0.046) as compared to the Gln27Gln group along the peak oxygen consumption trial intervention. There was a significantly lower fat oxidation (P = 0.024) in the Glu27Glu obese women during the recovery compared to Gln27Gln obese individuals. These data suggest that exercise would not benefit equally the two ADRB2 polymorphism homozygous groups, since both lipolysis and fat oxidation promoted by a peak oxygen consumption test appear to be blunted in the polymorphic Glu27Glu obese group.

Adipose Tissue↗

PubMed2003

A novel nonsense mutation in the melanocortin-4 receptor associated with obesity in a Spanish population.

BACKGROUND: In recent years, several groups have reported dominant inheritance of obesity conferred by missense, nonsense and frameshift mutations in the melanocortin 4 receptor gene (MC4R). Hence, MC4R is involved in the most common monogenic form of human obesity described so far. OBJECTIVES: In this context, we screened a Spanish population, composed of obese subjects and normal weight controls, for mutations in the MC4-R by single-strand conformational polymorphism (SSCP). SUBJECTS AND METHODS: Overall 313 individuals, 159 obese subjects (body mass index: BMI: 37.6 kg/m(2), 95% CI: 36.7-38.5 kg/m(2)) and 154 normal weight control subjects (BMI: 22.3 kg/m(2), 95% CI: 22.0-22.6 kg/m(2)) were screened for MC4-R mutations. RESULTS: We detected a novel nonsense mutation at codon 16 of the MC4-R in an obese female (BMI: 30.0 kg/m(2)) and a previously described missense mutation (Val-253-Ile) located within the sixth trans-membrane domain of the MC4-R in a normal weight individual (BMI: 19.0 kg/m(2)). The polymorphism Val-103-Ile was detected in one obese individual, while four subjects (two cases and two controls) with the polymorphism Ile-251-Leu were found. CONCLUSIONS: We have identified a novel nonsense mutation (Trp-16-Stop) that, based on previously described frameshift and nonsense mutations, most likely results in dominantly inherited obesity. Within this Spanish population, the frequency of the Ile-251-Leu polymorphism of the MC4R was similar in obese and control subjects (about 1.3%), while the polymorphism Val-103-Ile was only detected in an obese individual (0.6%).

Adult↗