Television viewing time and risk of eating disorders in Spanish adolescents: AVENA and AFINOS studies.

BACKGROUND: Effective preventive interventions for both eating disorders and obesity in adolescence should be focused on shared risk factors. We analyzed the association between television (TV) viewing time and the risk of eating disorders, as well as the potential role of obesity in this association. METHODS: The sample consisted of a total of 3458 Spanish adolescents, aged 13-18.5 years, from the Food and Assessment of the Nutritional Status of Adolescents (AVENA) and Physical Activity as a Preventive Measure of the Development of Overweight, Obesity, Allergies, Infections, and Cardiovascular Risk Factors in Adolescents (AFINOS) studies. Adolescents' TV time was assessed by self-report. Body mass index was calculated and the adolescents were classified into non-overweight and overweight-obesity. The risk of eating disorders was evaluated using the SCOFF questionnaire. RESULTS: Adolescents who watched TV >1 h/day had a higher risk for eating disorders, compared with those adolescents who watch TV <1 h/day. Also, overweight-obese adolescents had a higher risk for eating disorders than those who were non-overweight. Analyses across groups of TV viewing time and weight status showed similar trends, so that the higher the time spent in TV viewing, the higher the risk of eating disorders, regardless of weight status. CONCLUSIONS: TV viewing time might be a focal point for prevention of both eating disorders and obesity in adolescence.

Nutrition and physical activity programs for obesity treatment (PRONAF study): methodological approach of the project.

BACKGROUND: At present, scientific consensus exists on the multifactorial etiopatogenia of obesity. Both professionals and researchers agree that treatment must also have a multifactorial approach, including diet, physical activity, pharmacology and/or surgical treatment. These two last ones should be reserved for those cases of morbid obesities or in case of failure of the previous ones. The aim of the PRONAF study is to determine what type of exercise combined with caloric restriction is the most appropriate to be included in overweigth and obesity intervention programs, and the aim of this paper is to describe the design and the evaluation methods used to carry out the PRONAF study. METHODS/DESIGN: One-hundred nineteen overweight (46 males) and 120 obese (61 males) subjects aged 18-50 years were randomly assigned to a strength training group, an endurance training group, a combined strength + endurance training group or a diet and physical activity recommendations group. The intervention period was 22 weeks (in all cases 3 times/wk of training for 22 weeks and 2 weeks for pre and post evaluation). All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure estimated by accelerometry). 29-34% of the total energy intake came from fat, 14-20% from protein, and 50-55% from carbohydrates. The mayor outcome variables assesed were, biochemical and inflamatory markers, body composition, energy balance, physical fitness, nutritional habits, genetic profile and quality of life. 180 (75.3%) subjects finished the study, with a dropout rate of 24.7%. Dropout reasons included: personal reasons 17 (28.8%), low adherence to exercise 3 (5.1%), low adherence to diet 6 (10.2%), job change 6 (10.2%), and lost interest 27 (45.8%). DISCUSSION: Feasibility of the study has been proven, with a low dropout rate which corresponds to the estimated sample size. Transfer of knowledge is foreseen as a spin-off, in order that overweight and obese subjects can benefit from the results. The aim is to transfer it to sports centres. Effectiveness on individual health-related parameter in order to determine the most effective training programme will be analysed in forthcoming publications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01116856.

Excessive TV viewing and cardiovascular disease risk factors in adolescents. The AVENA cross-sectional study.

BACKGROUND: Excessive television (TV) viewing might play an important role in the development of cardiovascular disease (CVD). The aim of this study was to examine the independent associations between TV viewing and CVD risk factors in adolescents. METHODS: A sample of 425 adolescents, aged 13- to 18.5-year-old, was included in this study. Body mass index (BMI), waist circumference (WC), glucose, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein (apo) A-1, apo B-100, and lipoprotein(a) levels were determined. A composite CVD risk score was computed based on age-, sex-, sexual maturation- and race-standardized triglycerides, HDL-cholesterol, LDL-cholesterol and glucose. TV viewing was self-reported. RESULTS: Two hundred and twenty-five adolescents (53%) who spent >3 hrs/day watching TV were considered as the "high TV viewing" group. Ninety-nine adolescents (23%) from the total sample were classified as overweight according to International age- and sex-specific BMI values. The high TV viewing group had significantly less favorable values of HDL-cholesterol, glucose, apo A1 and CVD score, independent of age, sex, sexual maturation, race and weight status. There was a significant interaction effect of TV viewing x weight status (P = 0.002) on WC, and the negative influence of TV viewing on WC persisted in the overweight group (P = 0.031) but was attenuated in non-overweight adolescents (P > 0.05). CONCLUSION: Excessive TV viewing seems to be related to an unfavorable CVD risk factors profile in adolescence. Reducing TV viewing in overweight adolescents might be beneficial to decrease abdominal body fat.

Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study.

BACKGROUND: The prevalence of overweight and obesity (OW/OB) among adolescents worldwide has increased since the 60 s. Spain has reached one of the highest OW/OB prevalence rates among adolescents from European countries. The aim of this methodological paper is to describe the design and evaluation in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for adolescents with OW/OB: integral education on nutrition and physical activity). METHODS/DESIGN: The EVASYON was planned by a multidisciplinary team to treat OW/OB in Spanish adolescents. The EVASYON is a multi-centre study conducted in 5 hospitals in 5 Spanish cities (Granada, Madrid, Pamplona, Santander and Zaragoza) and two hundred and four OW/OB Spanish adolescents were recruited for this intervention. The treatment was implemented for approximately one-year follow-up. The adolescents were treated in groups of a maximum of 10 subjects; each group had 20 visits during the treatment period in two phases: intensive during the first 2 months (1st to 9th visits), and extensive during the last 11 months (10th to 20th visits). In order to assess the efficacy of the treatment, 8 dimensions were measured: diet; physical activity and fitness; eating behaviour; body composition; haematological profile; metabolic profile; minerals and vitamins; immuno-inflammatory markers. Moreover, genetic polymorphisms were also determined. DISCUSSION: The treatment programme developed in the EVASYON study was designed as a national pilot study to be implemented as an effective treatment for adolescents with OW/OB into the Spanish Health Care Service.

Interplay between weight loss and gut microbiota composition in overweight adolescents.

The aim of this study was to determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents. Thirty-six adolescents (13-15 years), classified as overweight according to the International Obesity Task Force BMI criteria, were submitted to a calorie-restricted diet (10-40%) and increased physical activity (15-23 kcal/kg body weight/week) program over 10 weeks. Gut bacterial groups were analyzed by quantitative real-time PCR before and after the intervention. A group of subjects (n=23) experienced >4.0 kg weight loss and showed significant BMI (P=0.030) and BMI z-score (P=0.035) reductions after the intervention, while the other group (n=13) showed <2.0 kg weight loss. No significant differences in dietary intake were found between both groups. In the whole adolescent population, the intervention led to increased Bacteroides fragilis group (P=0.001) and Lactobacillus group (P=0.030) counts, and to decreased Clostridium coccoides group (P=0.028), Bifidobacterium longum (P=0.031), and Bifidobacterium adolescentis (P=0.044) counts. In the high weight-loss group, B. fragilis group and Lactobacillus group counts also increased (P=0.001 and P=0.007, respectively), whereas C. coccoides group and B. longum counts decreased (P=0.001 and P=0.044, respectively) after the intervention. Total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts were significantly higher (P<0.001-0.036) while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum were significantly lower (P<0.001-0.008) in the high weight-loss group than in the low weight-loss group before and after the intervention. These findings indicate that calorie restriction and physical activity have an impact on gut microbiota composition related to body weight loss, which also seem to be influenced by the individual's microbiota.

Truncal and abdominal fat as determinants of high triglycerides and low HDL-cholesterol in adolescents.

We examined whether abdominal and truncal adiposity, assessed with simple anthropometric indices, determines serum triglycerides and high-density lipoprotein (HDL)-cholesterol levels independently of total adiposity amount in adolescents. A total of 547 Spanish adolescents (284 males and 263 females) aged 13-18.5 years were included in this study. Measures of truncal adiposity included subscapular to triceps ratio, and trunk-to-total skinfolds ratio (TTS%). Waist circumference was used as a surrogate of abdominal adiposity, and BMI was used as a measure of total adiposity. The results of the regression models indicated that levels of triglycerides were positively associated with waist circumference and TTS% after controlling for age and Tanner stage in both sexes. Once BMI was entered in the model, these associations remained significant for waist circumference in females. HDL-cholesterol levels were negatively associated with waist circumference in both sexes, and with subscapular to triceps ratio and TTS% in males, after controlling for age and Tanner stage. Once BMI was entered in the model, these associations remained significant for subscapular to triceps ratio and for TTS% in males. The results of this study suggest that in male adolescents, truncal adiposity is negatively associated with levels of HDL-cholesterol, whereas in females, abdominal adiposity is positively associated with levels of triglycerides independently of total adiposity. These findings highlight the deleterious effect of both truncal and abdominal fat depots on the lipid profile already from the first decades of life.

Methylenetetrahydrofolate reductase 677CT polymorphism and cobalamin, folate, and homocysteine status in Spanish adolescents.

BACKGROUND: Folate and cobalamin are responsible for healthy growth. However, the B-vitamin and homocysteine status of adolescents is not well known. The aim was to assess the status of folate, cobalamin, and homocysteine in healthy Spanish adolescents. METHODS: Serum cobalamin, serum folate, homocysteine, methylenetetrahydrofolate reductase 677C>T variant, BMI, smoking habits, and Tanner stage were determined according to gender in 165 adolescents (84 females, 81 males; 13-18.5 years) using the Student's t test, Mann-Whitney U test and chi(2) test, respectively. Interactions between socioeconomic status, age group, methylenetetrahydrofolate reductase polymorphism, BMI, smoking habits, Tanner stage, and vitamin status, respectively, were examined by ANOVA or Kruskal-Wallis H test (p < 0.05). RESULTS: Boys had markedly higher homocysteine (males 8.92 (5.51-22.94) micromol/l; females 7.91 (5.09-13.86) micromol/l), whereas girls showed higher serum cobalamin concentrations (males 540.00 (268.00-946.47) pmol/l; females 594.82 (280.63-1,559.64) pmol/l). Data are shown as medians and the 2.5th to 97.5th percentiles in parentheses. Adolescents with the homozygous variant of methylenetetrahydrofolate reductase displayed significantly higher homocysteine and lower serum folate: normal 5.73 (3.09-10.73) ng/ml serum folate, 7.57 (4.94-12.94) micromol/l homocysteine; homozygous 4.10 (2.75-7.88) ng/ml serum folate, 10.83 (7.00-22.82) micromol/l homocysteine. CONCLUSION: The present study provides data on the folate, cobalamin, and homocysteine status of Spanish adolescents. To assure a better assessment, revision of references for adolescents is still needed.

Effect of the Ala12 allele in the PPARgamma-2 gene on the relationship between birth weight and body composition in adolescents: the AVENA study.

The intent of this study was to assess whether the effect of birth weight on later body composition is modified by Pro12Pro, Pro12Ala, and Ala12Ala genotypes of the peroxisome proliferator-activated receptor gamma-2 (PPARgamma-2) gene. The PPARgamma-2 gene polymorphism was genotyped in 273 adolescents aged 13-18.5 y, born at term and whose birth weight was known. They were selected from a cross-sectional multicenter study conducted in five Spanish cities in 2000-2002. Body mass index (BMI) was calculated from weight and height measurements, and body composition and fat distribution were estimated from skinfold thickness. A total of 229 subjects (111 males and 118 females) carried the Pro12Pro genotype and 44 (22 males and 22 females) the Pro12Ala and Ala12Ala PPARgamma-2 genotypes. In the Pro12Pro group, birth weight Z score was positively associated with both fat-free mass (FFM) (p < 0.05) and fat mass (FM) (p < 0.05), but these relationships disappeared after controlling for age, gestational age, socioeconomic status (SES), physical activity, Tanner stage, sex, and BMI. In the Ala12 group, birth weight Z score was positively associated with FFM (p < 0.01), and this relationship remained significant after controlling for confounding variables (p < 0.05). Small body weight at birth may program lower FFM in adolescents carrying the Ala12 allele in the PPARgamma-2 gene.

[Lipid and metabolic profiles in adolescents are affected more by physical fitness than physical activity (AVENA study)]. / El perfil lipídico-metabólico en los adolescentes está más influido por la condición física que por la actividad física (estudio AVENA).

INTRODUCTION AND OBJECTIVES: To determine whether the level of physical activity or physical fitness (i.e., aerobic capacity and muscle strength) in Spanish adolescents influences lipid and metabolic profiles. METHODS: From a total of 2859 Spanish adolescents (age 13.0-18.5 years) taking part in the AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study, 460 (248 male, 212 female) were randomly selected for blood analysis. Their level of physical activity was determined by questionnaire. Aerobic capacity was assessed using the Course-Navette test. Muscle strength was evaluated using manual dynamometry, the long jump test, and the flexed arm hang test. A lipid-metabolic cardiovascular risk index was derived from the levels of triglycerides, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and glucose. RESULTS: No relationship was found between the level of physical activity and lipid-metabolic index in either sex. In contrast, there was an inverse relationship between the lipid-metabolic index and aerobic capacity in males (P=.003) after adjustment for physical activity level and muscle strength. In females, a favorable lipid-metabolic index was associated with greater muscle strength (P=.048) after adjustment for aerobic capacity. CONCLUSIONS: These results indicate that, in adolescents, physical fitness, and not physical activity, is related to lipid and metabolic cardiovascular risk. Higher aerobic capacity in males and greater muscle strength in females were associated with lower lipid and metabolic risk factors for cardiovascular disease.

El perfil lipídico-metabólico en los adolescentes está más influido por la condición física que por la actividad física (estudio AVENA) / Lipid and metabolic profiles in adolescents are affected more by physical fitness than physical activity (AVENA study)

Introducción y objetivos. Estudiar si la actividad física realizada o el grado de condición física (capacidad aeróbica y fuerza) que poseen los adolescentes españoles, están asociados con su perfil lipídico-metabólico. Métodos. Del total de 2.859 adolescentes españoles (13-18,5 años) evaluados en el estudio AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes), 460 (248 varones y 212 mujeres) fueron seleccionados aleatoriamente para un análisis sanguíneo. Se evaluó el grado de actividad física mediante cuestionarios. La capacidad aeróbica fue estimada a partir del test de Course-Navette. La fuerza muscular se valoró mediante una dinamometría manual, un salto de longitud y la flexión de brazos en una barra. Se calculó un índice lipídico-metabólico de riesgo cardiovascular según las concentraciones de triglicéridos, colesterol unido a lipoproteínas de baja densidad (cLDL), colesterol unido a lipoproteínas de alta densidad (cHDL) y glucosa. Resultados. La actividad física no mostró asociación con el índice lipídico-metabólico en ninguno de los dos sexos. El índice lipídico-metabólico se relacionó inversamente con la capacidad aeróbica en los varones (p = 0,003) tras ajustar por el grado de actividad física y la fuerza muscular. En las mujeres, un perfil lipídico-metabólico más cardiosaludable se asoció con una mayor fuerza muscular (p = 0,048) tras ajustar por la capacidad aeróbica. Conclusiones. Estos resultados indican que en la adolescencia es el grado de condición física, y no tanto la actividad física, lo que se relaciona con el perfil de riesgo lipídico-metabólico. Una alta capacidad aeróbica en varones y un alto grado de fuerza muscular en mujeres se asocian con un menor riesgo lipídico-metabólico de enfermedad cardiovascular (AU)

Introduction and objectives. To determine whether the level of physical activity or physical fitness (i.e., aerobic capacity and muscle strength) in Spanish adolescents influences lipid and metabolic profiles. Methods. From a total of 2859 Spanish adolescents (age 13.0­18.5 years) taking part in the AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study, 460 (248 male, 212 female) were randomly selected for blood analysis. Their level of physical activity was determined by questionnaire. Aerobic capacity was assessed using the Course­Navette test. Muscle strength was evaluated using manual dynamometry, the long jump test, and the flexed arm hang test. A lipid­metabolic cardiovascular risk index was derived from the levels of triglycerides, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and glucose. Results. No relationship was found between the level of physical activity and lipid­metabolic index in either sex. In contrast, there was an inverse relationship between the lipid­metabolic index and aerobic capacity in males (P=.003) after adjustment for physical activity level and muscle strength. In females, a favorable lipid­metabolic index was associated with greater muscle strength (P=.048) after adjustment for aerobic capacity. Conclusions. These results indicate that, in adolescents, physical fitness, and not physical activity, is related to lipid and metabolic cardiovascular risk. Higher aerobic capacity in males and greater muscle strength in females were associated with lower lipid and metabolic risk factors for cardiovascular disease (AU)

Cardiovascular fitness is negatively associated with homocysteine levels in female adolescents.

OBJECTIVE: To examine the association between cardiovascular fitness and homocysteine levels in adolescents. DESIGN: Cross-sectional study. SETTING: Madrid, Murcia, Granada, Santander, and Zaragoza, Spain. PARTICIPANTS: One hundred fifty-six Spanish adolescents (76 boys and 80 girls) aged (mean +/- SD) 14.8 +/- 1.4 years. MAIN EXPOSURES: Cardiovascular fitness was measured by the 20-m shuttle run test. Pubertal stage, birth weight, smoking status, and socioeconomic status were determined, and the sum of 6 skinfold thickness measurements, and serum folic acid and vitamin B(12) levels were measured. Methylenetetrahydrofolate reductase (MTHFR; 677C>T genotype) polymorphism was done by DNA sequencing. MAIN OUTCOME MEASURE: Fasting homocysteine levels. RESULTS: Mean values of homocysteine were significantly higher in the MTHFR 677CT and TT genotype subgroups compared with the CC genotype subgroup in adolescent boys, whereas in adolescent girls, mean values of homocysteine were significantly higher in the MTHFR 677CT and TT genotype subgroup compared with the CC and CT genotype subgroups. Multiple regression analyses showed that cardiovascular fitness was significantly associated with homocysteine levels in female adolescents after controlling for potential confounders including the MTHFR 677C>T genotype (beta = -0.40; semipartial correlation = -0.35; P = .007). No associations were found between cardiovascular fitness and homocysteine levels in male adolescents (beta = 0.12; semipartial correlation = 0.08; P = .51). CONCLUSION: The results suggest that cardiovascular fitness is negatively associated with homocysteine levels in female adolescents after controlling for potential cofounders including MTHFR 677C>T genotype.

Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation.

N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

Breast-feeding and risk of hospitalization for all causes and fever of unknown origin.

BACKGROUND: Breast-feeding has shown to give a reduction in the risk of hospitalization due to respiratory tract infections and gastrointestinal conditions during the first two years of life. The association of breast-feeding with all admission causes and with fever of unknown origin (FUO) was analysed. METHODS: A case-reference study in Cantabria (northern Spain) was carried out. Cases (n=336) were hospitalized children aged less than 24 months at University of Cantabria Hospital; the reference was a 1:1 matched (by time from delivery to admission) sample of children from mothers delivering at the same hospital. Information on breast-feeding, socioeconomic variables and employment were obtained. Odds ratios (ORs), their 95% confidence intervals (CIs), and mean length of breast-feeding were estimated after adjusment for confounding variables. RESULTS: In the reference population, shorter duration of breast-feeding was associated with smoking, lower educational level, and less privileged social strata. The frequency of breast-feeding was higher in the reference than in the cases, 82.3% vs 75.6% (p=0.023). Significant negative trends were noted in univariate analyses between the length of breast-feeding and both all admission causes and FUO, although the statistical significance was lost after adjusting for confounding variables (educational level, social class, smoking, and use of incubator after delivery). The adjusted mean length of breast-feeding was shorter in hospitalized children < or = 6 months old for both all admission causes (40.6 +/- 5.4 vs 99.5 +/- 5.4, p < 0.001) and FUO (40.8 +/- 12.4 vs 91.7 +/- 12.4, p=0.006). CONCLUSION: Breast-feeding time is shorter in hospitalized children for both all admission causes and FUO.

Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation.

Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24-73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients.

Long-chain polyunsaturated fatty acids in rat maternal milk, offspring brain and peripheral tissues in essential fatty acid deficiency.

Fatty acid status in humans is usually related to plasma or red blood cell fatty acid profiles. The aim of the study was to explore whether a maternal deficiency in dietary essential fatty acids would differentially affect lipid fractions in several tissues of the offspring, including brain. Female Wistar rats were fed an essential fatty acid-deficient diet during 3 months before mating. The fatty acid composition of different lipid fractions was examined in maternal milk, and in plasma, red blood cells, liver, adipose tissue, cerebral cortex and hippocampus of the offspring using thin layer and capillary column gas chromatography. Lipid fractions from most tissues of deprived offspring showed a common fatty acid profile characterized by elevated 20:3 omega9/20:4 omega6 ratio, and decreased docosahexaenoic acid and arachidonic acid. However, arachidonic acid was not affected in brain, even though 22:5 omega6 was increased in phospholipids of cerebral cortex and hippocampus. The present results demonstrate different degrees of resistance to essential fatty acid deficiency in lipid fractions and tissues. This suggests a priority distribution of arachidonic acid to preferential areas and shows that blood phospholipid fatty acids do not exactly reflect brain phospholipid status.

Expression and regulation of the transcriptional repressor ZNF43 in Ewing sarcoma cells.

In vitro, cells derived from Ewing sarcoma (ES) with the characteristic somatic rearrangement between the genes EWS and FLII can be induced to differentiate toward a neuronal phenotype by exposure to agents such as dibutyryl cyclic AMP (db cAMP) or retinoic acid. Therefore, expression of the chimeric Ews-Flil protein does not irreversibly block the capacity of Ewing cells to engage in the neuronal differentiation program initiated by these agents. To identify genes that might be involved in the maintenance of Ewing cells in their undifferentiated state, a PCR-based differential display method was used to compare gene expression patterns in Ewing cell lines with those induced to differentiate toward a neuronal phenotype. A cDNA was expressed at high levels in proliferating Ewing-derived EW-1 cells and downregulated in EW-1 cells induced to differentiate, which corresponds to ZNF43, a multi-zinc finger protein containing the Krüppel-associated box (KRAB) transcriptional repression domain. Treatment of EW-1 cells with antisense oligonucleotides complementary to ZNF43 mRNA induces morphological differentiation and growth arrest. These findings suggest a role for ZNF43 in the maintenance of ES cells in an undifferentiated state, and that ZNF43 could be a primary target for differentiation stimuli in Ewing cells.