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Made available in DSpace on 2022-05-01T08:15:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Mirabegron is a selective β₃-adrenergic receptors agonist, which has been recently shown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10–12. After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)-α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNF-α, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes. Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center Department of Physiology and Cell Biology The Ohio State University Wexner Medical Center Department of Physical Education Institute of Biosciences São Paulo State University (UNESP) Department of Pharmacology Faculty of Medical Sciences University of Campinas (UNICAMP) Department of Structural and Functional Biology Institute of Biology University of Campinas (UNICAMP) Medical School Graduate Program in Environmental Health Metropolitan University of Santos Department of Physical Education Institute of Biosciences São Paulo State University (UNESP)

© 2019 Annals of Pediatric Endocrinology & Metabolism. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited., Purpose: Acanthosis nigricans (AN) is a hyperpigmented dermatosis associated with obesity and insulin resistance (IR). There is no consensus whether AN extension scoring offers added value to the clinical estimation of IR. In this study we aimed to assess and score AN using both a short and an extended version of the scale proposed by Burke et al. and analyze the relationships of both versions with hyperinsulinemia and IR. Methods: We analyzed data from 139 overweight adolescents (body mass index ≥85th percentile) aged 12–18 with (n=67) or without (n=72) AN who were followed at a pediatric obesity clinic. Results: Adolescents with AN had higher levels of insulin (d=0.56, P=0.003) and HOMA-IR (d=0.55, P=0.003) compared to those without. Neither the short nor the extended versions of AN scores explained either hyperinsulinemia (β=1.10, P=0.316; β=1.15, P=0.251) or IR (β=1.07, P=0.422; β=1.10, P=0.374). The presence of AN alone predicted hyperinsulinemia and the presence of IR in 7.3% (β=2.68, P=0.008) and 7.1% (β=2.59, P=0.009) of adolescents, respectively. Conclusion: Screening for AN at the neck and axilla is a noninvasive and cost-effective way to identify asymptomatic overweight adolescents with or at risk of developing IR., AVS is supported by the Portuguese Foundation for Science and Technology (SFRH/BD/130193/2017).

Our previous studies show that cafeteria diet increases body adiposity, plasma insulin levels, and sympathetic activity to brown adipose tissue (BAT) and white adipose tissue (WAT) of Wistar rats, leading to rapid and progressive changes in the metabolic profile. The identification of suitable reference genes that are not affected by the experimental conditions is a critical step in accurate normalization of the reverse transcription quantitative real-time PCR (qRT-PCR), a commonly used assay to elucidate changes in the gene expression profile. In the present study, the effects of the cafeteria diet and sympathetic innervation on the gene expression of adrenoceptor beta 3 (Adrb3) from BAT and WAT were assessed using one of the most stable and one of the least stable genes as normalizers. Rats were fed the cafeteria diet and on the 17th day, interscapular BAT or retroperitoneal WAT was denervated and, 7 days after surgery, the contralateral innervated tissue was used as control. Ten reference genes were evaluated (18S, B2m, Actb, CypA, Gapdh, Hprt1, Rpl32, Tbp, Ubc, and Ywhaz) and ranked according to their stability using the following algorithms: geNorm, NormFinder, BestKeeper, and comparative delta threshold cycle (ΔC t ) method. According to the algorithms employed, the normalization of Adrb3 expression by the least stable genes produced opposite results compared with the most stable genes and literature data. In cafeteria and control diet-fed rats, the three most stable genes were Hprt1, Tbp, and Rpl32 for interscapular BAT and Tbp, B2m, and Hprt1 for retroperitoneal WAT, while the least stable genes were 18S, Actb, and Gapdh for both tissues.

Objective Chia seed oil is the richest source of plant-based ω-3 fatty acid, α-linolenic acid, but its potential and mechanisms of action to treat obesity are unclear. The aim of the study was to evaluate the effects of chia oil (ChOi) supplementation on body composition and insulin signaling in skeletal muscles of obese mice. Methods Male C57 BL/6 mice (n = 8/group) were fed regular control chow or a high-fat diet (HFD) for 135 d. Another HFD group additionally received ChOi from 90 to 135 d. Results Consumption of ChOi reduced fat mass accumulation and increased lean mass as evidenced by nuclear magnetic resonance. Moreover, obese mice treated with ChOi showed higher tyrosine phosphorylation of insulin receptor substrate 1, greater activation of protein kinase B, and increased translocation of glucose transporter type 4 in skeletal muscle tissue in response to insulin. ChOi supplementation improved glucose levels and insulin tolerance; decreased serum insulin, leptin, and triacylglycerols; and increased blood high-density lipoprotein cholesterol levels. All these effects caused by the use of ChOi seemed to be independent of the resolution of inflammation because the markers of inflammation were not altered in animals fed the HFD. Conclusion The molecular effects observed in muscle tissue together with changes in body composition may have contributed to the increased glucose tolerance and to the healthy phenotype presented by obese animals treated with ChOi.

The electron-transfer flavoprotein dehydrogenase gene (ETFDH) encodes the ETF-ubiquinone oxidoreductase (ETF-QO) and has been reported to be the major cause of multiple acyl-CoA dehydrogenase deficiency (MADD). In this study, we present the clinical and molecular diagnostic challenges, at the DNA and RNA levels, involved in establishing the genotype of four MADD patients with novel ETFDH variants: a missense variant, two deep intronic variants and a gross deletion. RNA sequencing allowed the identification of the second causative allele in all studied patients. Simultaneous DNA and RNA investigation can increase the number of MADD patients that can be confirmed following the suggestive data results of an expanded newborn screening program. In clinical practice, accurate identification of pathogenic mutations is fundamental, particularly with regard to diagnostic, prognostic, therapeutic and ethical issues. Our study highlights the importance of RNA studies for a definitive molecular diagnosis of MADD patients, expands the background of ETFDH mutations and will be important in providing an accurate genetic counseling and a prenatal diagnosis for the affected families.

Objectives The emergence of adolescent medicine (AM) as a specific area of training and health care delivery is progressing at various pace around the world. The objective of this exploratory survey was to inquire about the existence of official bodies and institutions offering recognition of the discipline as a specific field and on the status of related training initiatives. Methods A questionnaire was spread among a convenience sample of 21 colleagues involved in adolescent health care around the world, and answers were collected and analysed manually. Results All 21 colleagues from the North and South American, African, Asian and European regions have responded. Only seven countries report the existence of adolescent inpatient wards in some hospitals, while 16 have specialized outpatient clinics; in only eight countries is formal mandatory training in AM required for paediatricians; in seven others, such a stay is available but optional. Six countries have implemented a systematic assessment tackling AM in the certification process of paediatricians and just four recognize AM as a sub-specialty. Only two countries mention compulsory training in AM for family doctors. Fourteen countries report on the existence of an AM association. Conclusions Despite an encouraging number of initiatives testifying the growing place of AM in the practice of medicine, our data bring a worrisome portray of the status of AM in the involved countries and call for the development of appropriate health care and training centres.

Objectives Paediatricians increasingly need to take care of adolescents, a life stage with specific needs, however many of them admit a limitation in their medical education regarding Adolescent Medicine. The objective of this paperwork is to evaluate the formative model adopted in the Department of Paediatrics, Hospital de Santa Maria, and assess the impact of the training in Adolescent Medicine. Methods We surveyed the current Paediatric Residents and those who graduated as Paediatricians from the Department in the past five years, in order to get feedback on the one-month compulsory training at the Adolescent Medicine Division during their Residency. Results Both groups considered it as a very interesting/useful training. Paediatricians considered that the training had an insufficient duration, with statistical difference comparing to the current Residents’ opinion. Conversely, Residents considered more often that the acquired competencies would be useful in their future clinical practice, when compared to Paediatricians. Conclusions In order to potentiate learning and training during such a short period of time, a few changes were identified as beneficial to be implemented.

Objective The systemic function of CETP has been well characterized. CETP plasma activity reduces HDL cholesterol and thus increases the risk of atherosclerosis. Here, we investigated whether CETP expression modulate adiposity. Methods Body adiposity and energy metabolism related assays and gene/protein expression were compared in CETP transgenic and non-transgenic mice and in hamsters treated with CETP neutralizing antibody. Results We found that transgenic mice expressing human CETP present less white adipose tissue mass and lower leptinemia than nontransgenic (NTg) littermates. No differences were found in physical activity, food intake, fat fecal excretion, lipogenesis or exogenous lipid accumulation in adipose depots. Nonetheless, adipose lipolysis rates and whole-body energy expenditure were elevated in CETP mice. In accordance, lipolysis-related gene expression and protein content were increased in visceral and brown adipose tissue (BAT). In addition, we verified increased BAT temperature and oxygen consumption. These results were confirmed in two other animal models: 1) hamsters treated with CETP neutralizing antibody and 2) an independent line of transgenic mice expressing simian CETP. Conclusions These findings reveal a novel anti-adipogenic role for CETP.

Rational prescribing of medicines requires evidence from clinical trials on efficacy, safety and the dose to be prescribed, based on clinical trials. Regulatory authorities assess these data and information is included in the approved summary of product characteristics. Regulatory guidelines on clinical investigation of medicinal products in the paediatric population generally propose that studies are done in defined age groups but advise that any classification of the paediatric population into age categories is to some extent arbitrary or that the age groups are intended only as a guide. The pharmaceutical companies tend to plan their studies using age groups the regulatory guidelines suggest, to avoid problems when applying for marketing authorisation. These age bands end up in the paediatric label, and consequently into national paediatric formularies. The age bands of the most commonly used age-subsets: neonates, infant/toddlers, children and adolescents, are more historical than based on physiology or normal development of children. Particularly problematic are the age bands for neonates and adolescents. The age of 12 years separating children from adolescents, and the upper limit of the adolescents set by the definition of paediatric age in healthcare, which varies according to the region, are particularly questionable. Modern pharmacometric methods (modelling and simulation) are being increasingly used in paediatric drug development and may allow assessment of growth and/or development as continuous covariables. Maybe time has come to reconsider the rational of the currently used age bands.

In this chapter, we present the major advances in CETP research since the detection, isolation, and characterization of its activity in the plasma of humans and several species. Since CETP is a major modulator of HDL plasma levels, the clinical importance of CETP activity was recognized very early. We describe the participation of CETP in reverse cholesterol transport, conflicting results in animal and human genetic studies, possible new functions of CETP, and the results of the main clinical trials on CETP inhibition. Despite major setbacks in clinical trials, the hypothesis that CETP inhibitors are anti-atherogenic in humans is still being tested.

Social media use has become an integral part of children’s and adolescents’ lives. It has become a novel way of interaction among people and influences people’s social lives and public opinion as well as people’s purchasing decisions and businesses. Any website or platform that allows social interaction is considered to be a social media site. Social media use among children in 25 European countries has been reported to be 38% among 9–12 year olds and 77% among those aged 13–16 years. All these children report having their own profile on at least one social network site. While social networking provides children and adolescents with many opportunities and benefits, it also carries many risks. Among the benefits are socialization and communication enhancement, improving learning skills, positive impact on education and getting health information. Potential risks of social media use include falsifying age and identity, cyberbullying, sexting, Facebook depression, gamification, glamourization, cyberostracism and sleep disturbances. Conclusion: Paediatricians play a vital role in promoting the physical, mental and social welfare of all children. There is a critical need for paediatricians to play an active role, guiding children and families appropriately through the impact of social networking, in order to become a real driver of children’s development.

Background Adolescent overweight is a major public health concern, as it is associated with several short-run and long-run adverse health outcomes. Inappropriate health behaviours may be at the front of this epidemic. There is widespread need for new strategies that may positively influence dietary and physical activity behaviours. This trial (NCT02941770) was designed to investigate the impact of a physical activity consultation, based on motivational interview technique, on physical activity behaviour and weight status among overweight adolescents followed at a tertiary paediatric care centre. Methods/Design This is an ongoing non-randomised controlled clinical trial with a 6-month duration and follow-up at month 12. It is expected to be concluded in December 2018. Adolescents (n=129) aged 12–18 with a body mass index ≥p85 are recruited and allocated into three groups: (1) control group: standard care (paediatric and nutrition consultations, n=43); (2) experimental group I: standard care plus physical activity consultation (n=43); and (3) experimental group II: exposure to two sessions/week of structured physical exercise, in addition to the standard care plus physical activity consultations (n=43). Sample size was calculated according to power analysis. Participants undergo a set of socioeconomic, anthropometric, body composition, clinical and behavioural (dietary and physical activity) assessments. Discussion Adolescence is a critical period for the acquisition of a healthy lifestyle. The promotion of an active lifestyle may influence adolescents’ weight status and further prevent multiple comorbidities. The findings of our study will provide further understanding on the impact of a physical activity consultation on physical activity behaviour and weight reduction/maintenance among overweight adolescents. Trial registration number NCT02941770.

This study aimed to analyze the associations between sedentary behavior, physical activity (PA), and cardiorespiratory fitness (CRF), with carotid intima-media thickness (cIMT), a marker of atherosclerosis already present at an early stage among obese adolescents. The associations between anthropometric measures, sedentary time, PA, CRF, and cIMT of 54 Caucasian obese adolescents were analyzed using partial correlations (controlling for age and sex) and multiple linear regressions. Differences between participants with and without a healthy CRF were also analyzed using independent sample t test. Sedentary time did not correlate with any of the variables. Light physical activity correlated positively with mean cIMT (r(38) = 0.36, p = 0.024). Moderate physical activity (MPA) correlated positively with both mean (r(38) = 0.37, p = 0.018) and maximum (r(38) = 0.33, p = 0.039) cIMT. CRF was inversely associated with mean cIMT (r(40) = −0.36, p = 0.019), even when controlling for sedentary time (r(37) = −0.35, p = 0.030). The best predictors of cIMT were MPA and weight. No significant differences in cIMT were found between participants with healthy and unhealthy CRF. Conclusion: Although we need to be cautious due to the limitations of the study, the results suggest that despite the importance of decreasing sedentary time, increasing PA intensity may be more effective in improving endothelial structural health among obese adolescents.

Motivational interviewing (MI) is an effective method to promote weight loss that can be delivered by non-mental health providers. The aim of this study was to evaluate whether MI was superior to conventional counseling to improve the anthropometric outcomes of adolescents with obesity/overweight. It was a controlled cluster randomized trial with parallel design in a school setting. The study included two groups: Motivational Interviewing Group (MIG) and control group (Conventional Intervention Group, CIG). Students participated in three face-to-face 30-min interviews, 3 months apart. Outcomes were BMI z-score, abdominal circumference, percentages of fat mass and muscle mass, and blood pressure. Sessions were coded with the Motivational Interviewing Treatment Integrity (MITI) manual. Mixed repeated-measures ANOVAs were used to assess the group versus time interaction. Effect sizes were calculated for each ANOVA with eta-squared measures (η2). Eighty-three adolescents finished the protocol. While MIG participants showed a significant improvement in all anthropometric scores at 6 months, CIG participants showed an unfavorable change in those variables. Conclusion: Our results provide additional evidence of the short-term usefulness of a school-based MI intervention on anthropometric outcomes of adolescents with obesity/overweight, demonstrating that pediatricians can play an important role in the prevention and management of pediatric obesity. Trial registration: The study is called IMAGINE and is registered in Clinicaltrials.gov with the number NCT02745795.

We have previously shown that the cafeteria diet increases body fat mass, plasma triacylglycerol (TAG) and insulin levels, glucose uptake by white and brown adipose tissues, as well as the sympathetic activity to both adipose tissues in Wistar rats. The metabolic pathways responsible for the development of non-alcoholic fatty liver disease (NAFLD) were examined in cafeteria diet-fed rats. After 3 weeks offering cafeteria diet, we evaluated: (i) activity of the sympathetic nervous system by norepinephrine turnover rates; (ii) de novo fatty acid synthesis in vivo using 3H2O; (iii) secretion of very low density lipoprotein (VLDL)-TAG secretion measuring serum TAG levels after administration of lipase lipoprotein inhibitor, (iv) liver cytosolic lipases activities and (v) liver mRNA expression of enzymes involved in lipids secretion and oxidation by RT-PCR. The cafeteria diet induced an increase in TAG (120%) and cholesterol (30%) liver contents. Cafeteria diet did not change the sympathetic nervous system activity to liver, but induced a marked increase in the lipogenesis (approximately four-fold) and significant increase in cytosolic lipases activities (46%) and VLDL-TAG secretion (22%) compared to control diet-fed rats. The cafeteria diet also increased the microsomal triglyceride transfer protein (30%) and carnitine palmitoyltransferase I (130%) mRNA expression but decreased the apolipoprotein B100 (26%) mRNA expression. Our findings demonstrate that the increase in the cytosolic lipases activities and VLDL-TAG secretion rates were not able to compensate for the increased lipogenesis rates induced by the cafeteria diet, resulting in NAFLD.

© 2018 Elsevier B.V. All rights reserved, To compare motivational interviewing (MI) with conventional care regarding the health-related quality-of-life (HRQoL) of adolescents with overweight/obesity. Methods: RCT with parallel design, involving two groups: intervention group (MI group [MIG]) and control group (conventional intervention group [CIG]). The intervention included three 30-minute interviews 3 months apart. Outcome: Change in Pediatric Quality of Life Inventory (PedsQL) scores. A mixed repeated-measures analysis of variance was used to assess group versus time interactions. Results: Eighty-three participants finished the protocol (82% girls). MIG participants showed a significant average increase (+4.7) on the Psychosocial (t[41] = -2.388, p = .022, d = .37) and Emotional Subscales (+5.1) (t[41] = 5.733, p < .001, d = .88). CIG participants showed a significant average decrease on the Psychosocial (-6.1) (t[40] = 5.733, p < .001, d = .90), Emotional (-14.1) (t[40] = 7.249, p < .001, d = 1.13) and Social Subscales (-3.8) (t[40] = 3.782, p = .001, d = .59) and on the Total Score (–4.4) (t[40] = 3.535, p = .001, d = .55) Conclusion: MI improved HRQoL among overweight adolescents participating in a weight management program. Practice implications: MI increases HRQoL and has the potential to benefit weight management programs for adolescents.

In many European countries, paediatric junior staff has no formal training in adolescent medicine and is ill-equipped to deal with issues and health problems such as substance use, unprotected sex, eating disorders and transition to adult care. This position paper of the European Academy of Paediatrics proposes a set of competency-based training goals and objectives as well as pedagogic approaches that are expected to improve the capacity of paediatricians to meet the needs of this important segment of the paediatric population. The content has been developed from available publications and training programmes and mostly covers the generic aspects of adolescent healthcare, such as how to communicate effectively, how to review and address lifestyles, how to perform a respectful and relevant physical examination, how to address common problems of adolescents and how to support adolescents in coping with a chronic condition. Conclusion: The European Academy of Paediatrics urges national bodies, paediatric associations and paediatric teaching departments to adopt these training objectives and put them into practice, so that paediatricians will be better prepared in the future to meet the challenge of delivering appropriate and effective healthcare to adolescents.

Objective Birth prevalence of Cobalamin (Cbl) C or D defects in Portugal is an estimated 1:85,000, one of the highest worldwide. We compared the genotype/phenotype of patients identified with CblC or CblD before and after the implementation of expanded newborn screening. Methods Twenty-five Portuguese CblC/D patients, 14 symptomatic and 11 identified through screening, were diagnosed using gas chromatography or tandem mass spectrometry. Molecular characterization was performed through the study of MMACHC and MMADHC genes. Results The most common MMACHC mutation, c.271dupA, was present in 100% of MMACHC alleles of all CblC screened patients, in contrast with the 61% identified before expanded newborn screening. All studied cases (except one, who presented a CblD deficiency) presented a CblC defect. More CblC late-onset patients were diagnosed before the introduction of newborn screening than in the post newborn screening era, probably because some early onset patients died without a definitive diagnosis. Conclusion The molecular data found in this cohort contribute to the improvement of screening and diagnosis of Cbl defects and would enable a confirmatory diagnosis of these patients, reducing the need for complex, costly, laborious, and time-consuming biochemical/enzymatic tests.

BACKGROUND Investigating life-stage factors associated with overweight may be useful in the prevention of excessive BMI increase. The main aim of this study was to investigate the influence of the route of delivery, birth weight and overweight onset on overweight severity in a sample of overweight adolescents followed at a Pediatric Obesity Clinic. METHODS Clinical data from 412 adolescents with overweight (BMI ≥ p85), aged 10-18 were retrospectively collected and analyzed. RESULTS Adolescents born by cesarean section (CS) showed a lower age of overweight onset, compared to other methods of delivery (d= 0.33, p= .009). Birth weight was positively associated with BMI z-score (r=.164, p= 002) and waist circumference (WC) (r=.191, p=.001). The overweight onset was negatively associated with BMI z-score (r= -.277, p < .001), WC (r= -.270, p < .001) and body fat mass (r= -.199, p=.001). Overweight duration was the best predictor of BMI z-score, explaining in 75% its variation (F=1,317)=26.94, p < .001), which increased to 99% when birth weight was included in the model (F(2,316)=18.47, p < .001). CONCLUSIONS This study suggests that lifestyle may interrupt the burden of CS on BMI z-score throughout growth. Moreover, increased birth weight may anticipate overweight onset, and consequently overweight duration in the presence of inadequate lifestyle behaviors.

Cholesteryl ester transfer protein (CETP) is a plasma protein that reduces high density lipoprotein (HDL)-cholesterol (chol) levels and may increase atherosclerosis risk. n-3 and n-6 polyunsaturated fatty acids (PUFAs) are natural ligands, and fibrates are synthetic ligands for peroxisome proliferator activated receptor-alpha (PPARα), a transcription factor that modulates lipid metabolism. In this study, we investigated the effects of PUFA oils and fibrates on CETP expression. Hypertriglyceridemic CETP transgenic mice were treated with gemfibrozil, fenofibrate, bezafibrate or vehicle (control), and normolipidemic CETP transgenic mice were treated with fenofibrate or with fish oil (FO; n-3 PUFA rich), corn oil (CO, n-6 PUFA rich) or saline. Compared with the control treatment, only fenofibrate significantly diminished triglyceridemia (50%), whereas all fibrates decreased the HDL-chol level. Elevation of the CETP liver mRNA levels and plasma activity was observed in the fenofibrate (53%) and gemfibrozil (75%) groups. Compared with saline, FO reduced the plasma levels of nonesterified fatty acid (26%), total chol (15%) and HDL-chol (20%). Neither of the oil treatments affected the plasma triglyceride levels. Compared with saline, FO increased the plasma adiponectin level and reduced plasma leptin levels, whereas CO increased the leptin levels. FO, but not CO, significantly increased the plasma CETP mass (90%) and activity (23%) as well as increased the liver level of CETP mRNA (28%). In conclusion, fibrates and FO, but not CO, up-regulated CETP expression at both the mRNA and protein levels. We propose that these effects are mediated by the activation of PPARα, which acts on a putative PPAR response element in the CETP gene.

Fatty acid synthase (FASN) is the biosynthetic enzyme responsible for the endogenous synthesis of fatty acids. It is downregulated in most normal cells, except in lipogenic tissues such as liver, lactating breast, fetal lung, and adipose tissue. Conversely, several human cancers, including head and neck squamous cell carcinomas (HNSCC), overexpress FASN, which has been associated with poor prognosis and recently suggested as a metabolic oncoprotein. Orlistat is an irreversible inhibitor of FASN activity with cytotoxic properties on several cancer cell lines that inhibits tumor progression and metastasis in prostate cancer xenografts and experimental melanomas, respectively. To explore whether the inhibition of FASN could impact oral tongue squamous cell carcinoma (OTSCC) metastatic spread, an orthotopic model was developed by the implantation of SCC-9 ZsGreen LN-1 cells into the tongue of BALB/c nude mice. These cells were isolated through in vivo selection, show a more invasive behavior in vitro than the parental cells, and generate orthotopic tumors that spontaneously metastasize to cervical lymph nodes in 10 to 15 days only. SCC-9 ZsGreen LN-1 cells also exhibit enhanced production of MMP-2, ERBB2, and CDH2. The treatment with orlistat reduced proliferation and migration, promoted apoptosis, and stimulated the secretion of VEGFA165b by SCC-9 ZsGreen LN-1 cells. In vivo, the drug was able to decrease both the volume and proliferation indexes of the tongue orthotopic tumors and, importantly, reduced the number of metastatic cervical lymph nodes by 43%. These results suggest that FASN is a potential molecular target for the chemotherapy of patients with OTSCC. Mol Cancer Ther; 13(3); 585–95. ©2013 AACR.

Several studies have shown that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases, diabetes, and cancer, mainly due to the presence of dietary fiber (DF) and polyphenols. Taioba (Xanthosoma sagittifolium) is an edible aroid widely grown in many parts of Africa, America, and Asia. The tubers portions of taioba are widely consumed; however, the leafy portions are generally discarded, despite their high nutritive value. In this study, we have partly characterized the DF of lyophiized taioba leaf (LTL), and assessed the possible protective effects on biochemical parameters and on bile acid (BA) production in colon and cecum, when fed to healthy rats for 4 wk. Forty-five Wistar rats were assigned to either of 5 groups: group 1 received AIN 93G diet (CG: Control); group 2 received AIN 93G containing 2.5% of cellulose + 2.5% inulin (CEIN_5%); group 3 received AIN 93G containing 2.5% of cellulose + 2.5% taioba fiber (CETA_5%); group 4 received AIN 93G containing 5% cellulose + 2.5% taioba fiber (CETA_7.5%); group 5 received AIN 93G containing 5% cellulose + 2.5% of inulin (CEIN_7.5%). LTL showed high contents of total fiber, predominantly comprising insoluble DF with glucose as the major monomer. Rats receiving LTL had increased fecal mass and fat excretion, and improved BA profiles by diminishing the proportion of secondary acids, thus suggesting that consumption of taioba leaf may have the property of lowering the risk of colon cancer.

Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with thead libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in thead libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid β-oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions-c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)-were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.

The consumption of vegetables has been correlated with reduced risk of chronic non-communicable diseases due to the high fiber content and bioactive compounds found in vegetables. The arrowleaf elephant ear (Xanthosoma sagittifolium), which is known in Brazil as taioba, is a common plant in tropical America. Although its leafy portion possesses a high nutritional value, it is not widely consumed and has not been well studied. This study assessed the effect of lyophilised taioba leaf (LTL) as a hypolipidemic and prebiotic agent. Thirty-two Wistar rats were assigned to four groups: group 1 was fed a high-fat diet containing 3.67% (w/w) cellulose (low cellulose — LCEL); group 2 received a high-fat diet supplemented with 10% (w/w) cellulose (CEL); group 3 received a high-fat diet supplemented with 10% (w/w) inulin (INU); and group 4 was fed a high-fat diet supplemented with 28.4% LTL (TAI) to provide 10% (w/w) taioba fiber. The groups were fed their respective diets for 4weeks. The addition of LTL to the diet resulted in reduced weight gain, reduced liver fat, and increased fecal mass and lipid, in addition to higher fecal short chain fatty acid and bile salt concentrations, compared to the LCEL group. Additionally, only the TAI group exhibited a lower serum cholesterol concentration and a higher body ash content (p

Overweight is an extra burden for adolescent development and can trigger severe physical and psychosocial problems. This cross-sectional correlational study aimed to analyze the association between treatment adherence and obesity-related quality of life among overweight adolescents. The sample consisted of 94 adolescents attending a specialized Pediatric Obesity Clinic in Portugal, 48.94% of whom were boys and 51.06% girls, with a median age of 14.17 years (SD = 1.51). A positive correlation was found between obesity-related quality of life and adherence to weight control. The influence of parents and caregivers on the adherence to weight control is significantly associated with increased physical comfort, better social life and family relations. These results highlight the importance of behavioral change and adherence to weight control as pillars of a better quality of life among overweight adolescents. Obesity management programs need to focus on multiple criteria of treatment effectiveness, such as obesity-related quality of life. O sobrepeso representa um ônus adicional para o desenvolvimento do adolescente e pode provocar problemas físicos de psicossociais. Este estudo correlacional transversal teve como objetivo analisar a associação entre adesão terapêutica e qualidade de vida associada à obesidade entre adolescentes com sobrepeso. A amostra consistia em 94 adolescentes que frequentavam uma clínica pediátrica especializada em obesidade em Portugal (48,94% meninos; 51,06% meninas), com mediana de idade de 14,17 anos (DP = 1,51). Foi demonstrada uma correlação positiva entre qualidade de vida relacionada à obesidade e adesão ao controle de peso. O estudo mostra uma associação positiva entre a influência dos pais e cuidadores sobre a adesão ao controle de peso e o aumento do conforto físico e a vida social e relações familiares. Os resultados destacam a importância de mudanças comportamentais e adesão ao controle de peso como pilares para uma melhor qualidade de vida entre adolescentes com sobrepeso. Os programas para o manejo da obesidade devem priorizar múltiplos critérios de efetividade terapêutica, tais como qualidade de vida relacionada à obesidade. El sobrepeso representa una carga adicional para el desarrollo del adolescente y puede provocar problemas físicos y psicosociales. Este estudio correlacional transversal tuvo como objetivo analizar la asociación entre adhesión terapéutica y calidad de vida, asociada a la obesidad entre adolescentes con sobrepeso. La muestra consistía en 94 adolescentes que frecuentaban una clínica pediátrica, especializada en obesidad en Portugal (48,94% niños; 51,06% niñas), con una media de edad de 14,17 años (DP = 1,51). Se demostró una correlación positiva entre calidad de vida relacionada con la obesidad y adhesión al control de peso. El estudio muestra una asociación positiva entre la influencia de los padres y cuidadores sobre la adhesión al control de peso y el aumento de confort físico, la vida social y relaciones familiares. Los resultados destacan la importancia de cambios comportamentales y de adhesión al control de peso como pilares para una mejor calidad de vida entre adolescentes con sobrepeso. Los programas para el manejo de la obesidad deben priorizar múltiples criterios de efectividad terapéutica, tales como calidad de vida relacionada con la obesidad.

This is the pre-peer reviewed version of the following article: [Cross-sectional study showed psychosocial variables, gender and family involvement played an important role in an adolescent weight management programme], which has been published in final form at [10.1111/apa.13616]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Aim: This study aimed to investigate the psychosocial gains perceived by overweightadolescents attending a 12-week weight management programme and to analyse gender-specific differences. Methods: A quantitative cross-sectional study was conducted with a sample of 70overweight adolescents aged between 12 and 18 (52.9% girls), evaluated at baseline andat week 12 using anthropometric measurements and self-reported questionnaires. Weanalysed gender-specific differences related to body self-esteem, social life, relationshipswith their family, physical comfort, health responsibility, perceived benefits of theintervention, self-efficacy and adherence. We further investigated whether the variables atweek 12 would predict changes in their body mass index. Results: While weight had a greater impact on the body self-esteem of girls, both atbaseline and week 12, boys reported higher self-efficacy and adherence as well as agreater perception of the benefits of the intervention at week 12. The body mass indexchange was positively associated with body self-esteem, relationships within the family andself-efficacy and adherence. Conclusion: Gender specifics and the role of psychosocial variables must be taken intoaccount during weight management programmes for adolescents, and it is important toinclude the family throughout the entire process. info:eu-repo/semantics/publishedVersion

Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFαreceptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα(8-fold) and IL-6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase-3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low-fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet-induced NAFLD.

Background: Adolescence includes a period (10 to 19 years) of profound biopsychosocial changes, constituting potentially difficult challenges, which may become more pronounced in the presence of a chronic condition and its limitations. Responses are not homogeneous and can be quite variable, depending on various specific individual factors. Research comparing adolescents with or without chronic illness, or comparing across different conditions, has been contradictory, not confirming a direct relationship between the degree of suffering and the chronic condition. Objective: To characterize and assess the impact of 1) having a chronic condition (CC) and 2) how CC affects school participation; and its association with life satisfaction and perception of wellness, controlling for demographic factors: age, gender and family socioeconomic status (SES). Methods: 5050 Portuguese adolescents with an average age of 14 years participated in the Health Behaviour in School-aged Children/WHO (HBSC). Results: The majority of the adolescents with CC reported that their conditions did not affect school participation. Adolescents with CC who indicated that CC affected school participation felt more frequently unwell and presented lower life satisfaction. Being a boy, younger and having high family socio economic status (SES) were identified as predictors of higher life satisfaction; on the other hand, being a girl, older, having lower SES, living with CC and feeling that CC affects school participation are predictors for feeling more frequently unwell. Conclusions: These adolescents showed an increased vulnerability, presenting internalized symptoms and lower life satisfaction. Furthermore, when there was simultaneous occurrence of living with CC and that CC affected school participation, the impact was even higher. Thus, it is crucial that future interventions should include the identified predictors, combined with “listen to the voice” of adolescents, throughout the adaptation process.

Adolescents have specific characteristics, capabilities, and needs that evolve throughout the second decade of life. Many behaviours initiated during adolescence (unprotected sex, physical inactivity, the use of tobacco, alcohol, and illicit drugs) have important consequences for health in adulthood. Even so, there is evidence that positive interventions during adolescence can avert negative outcomes in adulthood. Improvement of global adolescent health is an important challenge and opportunity faced by all countries. In light of this, the education of tomorrow’s medical doctors must in our view include adolescent health as well as the acquisition of communication and interdisciplinary approach skills. WHO strongly advocates that every provider working with adolescents should have core competencies in adolescent health, and further promotes a competency based training in adolescent health and development. At the Lisbon Academic Medical Center which includes the Faculty of Medicine of Lisbon, Santa Maria University Hospital, and the Institute of Molecular Medicine, measures were undertaken in order to train medical students, pediatricians, and health professionals in general in Adolescent Health and Medicine. Adolescent Medicine started by being taught as a stand-alone course but little by little became a part of the general flow of the pediatric curriculum both at the pre- and postgraduate training. The four initiatives that took place in this context will be described and discussed in this chapter: (i) Adolescent Medicine Elective Course for Medical Students (2000–); (ii) Inclusion of Adolescent Medicine in the discipline of Pediatrics I (2011–); (iii) Master Degree in Adolescent Health (2010–2015); (iv) Fellowship in Adolescent Medicine (2014–).

Background: In order to understand the mechanisms involved in how overweight adolescents adhere to weight management and perceive its benefits, a few variables have been identified, namely, body mass index (BMI), body self-esteem (BSE) and positive perspective of life (PPL). Methods: In a sample of 112 adolescents, we investigated whether BMI would predict adolescents’ self-efficacy/adherence (SEA) to weight management and perception of its benefits. A structural equation modeling approach was chosen. We hypothesized that perceived quality of life (PQL) would mediate the relationships between BMI and SEA and between BMI and perception of benefits (PB). Results: The results suggested that BMI is not directly associated with SEA and PB. However, PQL was identified as a mediator between BMI and SEA and PB. Conclusion: These findings bring important implications for understanding overweight adolescents’ adherence to weight management. There is evidence that adolescents’ adherence to weight management and PB are not predicted by their BMI. However, it has been shown that PQL mediates this process. For a long time, health professionals have been too focused on BMI. Time has come to be more focused on quality of life and how to improve it.

The deficiency of 3-methycrotonyl-CoA carboxylase (3-MCC; EC 6.4.1.4) is an autosomal recessive organic aciduria that is included in the newborn screening programs of several countries. This study reports data mainly obtained from the Portuguese newborn screening program collected over a ten-year period. Analysis of the MCCC1 and MCCC2 genes yielded 26 previously unreported mutations and a variant of clinically unknown significance. These mutations are discussed in the context of their likely impact on the function of the 3-MCC enzyme, with a view to exploring whether a phenotype-genotype correlation might be discerned. Further, these mutations were analysed in the context of what is known of the MCCC1 and MCCC2 mutational spectra, information that will be useful in both clinical and laboratory practice.

Nutritional recovery with a soyabean diet decreases body and fat weights when compared with a casein diet. We investigated whether the reduced adiposity observed in rats recovering from early-life malnutrition with a soyabean diet results from alterations in lipid metabolism in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Male rats from mothers fed either 17 or 6 % protein during pregnancy and lactation were maintained on 17 % casein (CC and LC groups), 17 % soyabean (CS and LS groups) or 6 % casein (LL group) diets over 60 d. The rats maintained on a soyabean diet had similar relative food intakes, but lower body and retroperitoneal WAT weights and a reduced lipid content in the retroperitoneal WAT. The insulin levels were lower in the recovered rats and were elevated in those fed a soyabean diet. Serum T3 concentration and uncoupling protein 1 content in the BAT were decreased in the recovered rats. The thermogenic capacity of the BAT was not affected by the soyabean diet. The lipogenesis rate in the retroperitoneal WAT was similar in all of the groups except for the LL group, which had exacerbated lipogenesis. The enhancement of the lipolysis rate by isoproterenol was decreased in white adipocytes from the soyabean-recovered rats and was elevated in adipocytes from the soyabean-control rats. Thus, in animals maintained on a soyabean diet, the proportions of fat deposits are determined by the lipolysis rate, which differs depending on the previous nutritional status.

Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid, palmitate. In contrast to most normal cells, FASN is overexpressed in a variety of human cancers, including cutaneous melanoma, in which its levels of expression are associated with tumor invasion and poor prognosis. We have previously shown that FASN inhibition with orlistat significantly reduces the number of spontaneous mediastinal lymph node metastases following the implantation of B16-F10 mouse melanoma cells in the peritoneal cavity of C57BL/6 mice. In this study, we investigate the biological mechanisms responsible for the FASN inhibition-induced apoptosis in B16-F10 cells. Both FASN inhibitors, cerulenin and orlistat, significantly reduced melanoma cell proliferation and activated the intrinsic pathway of apoptosis, as demonstrated by the cytochrome c release and caspase-9 and -3 activation. Further, apoptosis was preceded by an increase in both reactive oxygen species production and cytosolic calcium concentrations and independent of p53 activation and mitochondrial permeability transition. Taken together, these findings demonstrate the mitochondrial involvement in FASN inhibition-induced apoptosis in melanoma cells.

INTRODUCTION: The Portuguese Neonatal Screening Programme (PNSP) was started in 1979 for phenylketonuria (2,590,700 newborns screened; prevalence 1:11,031) and, shortly after, for congenital hypothyroidism (2,558,455 newborns screened; prevalence 1:3,174). In 2004, expanded neonatal screening was implemented in the National Laboratory. The programme is not mandatory and has 99.8% coverage of the country (including Madeira and the Azores islands). MATERIAL AND METHODS: In the past 4 years, 316,243 neonates were screened with the use of tandem mass spectrometry (MS/MS) to test for selected amino acids and acylcarnitines. RESULTS: During this time, 132 patients were identified with 24 different inherited metabolic diseases (classic forms and variants). To date, the global frequency for all disorders integrated into the PNSP is estimated to be 1:1,380, with 1:2,396 for metabolic disorders. A total of 379 tests (0.12%) were classified as having false positive results, yielding an overall specificity of 99.9%. Despite the low frequency of several disorders, the positive predictive value of the overall MS/MS screening was found to be 26%, reflecting high diagnostic specificity of the method. Diagnostic sensitivity of extended screening for the different groups of disorders was 100%. Eight cases of maternal disorders [three glutaric aciduria type I, one carnitine transporter defect, and four 3-methylcrotonyl coenzyme A (CoA) carboxylase deficiency] were also detected through newborn screening. CONCLUSIONS: Our data support the advantage of a centralised laboratory for screening an elevated number of samples and making decisions if relying on a clinical network able to provide fast treatment and a good outcome in the screened cases.

In order to determine the prevalence of metabolic syndrome (MS) in a Portuguese pediatric overweight population according to three different sets of criteria, 237 overweight and obese adolescents were evaluated at engagement in a specific multidisciplinary program. Two of the used definitions were based on the National Cholesterol Education Program (ATPIII) guidelines modified for pediatric age and were proposed by Cook et al. (Arch Pediatr Adolesc Med 157(8):821–827, 2003) and de Ferranti et al. (Circulation 110(16):2494–2497, 2004). The third definition used resulted from a consensus of the International Diabetes Federation (IDF 2005). All of them include five components: waist circumference, blood pressure, high-density lipoprotein cholesterol, triglycerides, and fasting glucose values, with different cut-off points. Of the studied sample, 53% were girls, median age 13.4 years, 89% classified as obese, and the remaining as overweight. MS prevalence was 15.6%, 34.9%, and 8.9% according to Cook’s, de Ferranti's, and IDF definitions, respectively. No adolescent fulfilled the five MS criteria, and only three (1.2%), 15 (6%), and 13 (5.1%) had no criteria at all, according to the three definitions used. Waist circumference was the most prevalent component (89.5%, 98.7%, and 93.2%), and high fasting glucose the least (1.3% for the two first and 2.5% according to the IDF definition). A significant correlation between increased body mass index and MS was found, using the two first definitions (Cook et al. p < 0.05; de Ferranti et al. p < 0.01), but not when using the third one. Considerable prevalence differences were found using three different MS criteria. It is urgent to establish a consensus on MS definition to allow early identification of adolescents at risk and the development of prospective studies to define what cut-offs are the best indicators of future morbidity.

AIM: To examine correlates of unhealthy weight-control behaviours (UNWCB), and to explore possible associated variables. METHODS: Sample included 3762, 8th and 10th grade public school Portuguese students who participated in the 2002 Health Behaviour in School-Aged Children (HBSC)/World Health Organization (WHO) survey of adolescent health. Factor analysis was used, and two scales were identified as 'healthy weight-control behaviours' (HWCB) and 'UNWCB' through Kaiser criteria analysis. Frequency scores were developed and used in analysis of variance (ANOVAs) test as dependent variables, according to gender and age. Pearson correlations and post-hoc analysis were performed to identify potential associations. RESULTS: UNWCB were significantly higher among those who were dieting or not dieting, but considering they should, and were significantly and progressively increasing from those perceiving themselves as thin, to those perceiving themselves as being the right size and those perceiving themselves as fat. Overweight reported more frequently than non-overweight, both HWCB and UNWCB. Finally, there were significant differences concerning alcohol use, with UNWCB increasing progressively from reporting 'drinking rarely or never' to 'drinking every week' and 'everyday'. CONCLUSION: Because UNWCB are associated with both medical and psychological health risks, routine screening is warranted. Special attention needs to be directed towards youth at greatest risk for disordered eating, including overweight youth. Language: en

Fatty acid synthase (FASN) is the enzyme responsible for the endogenous synthesis of the saturated fatty acid palmitate. In contrast to most normal cells, malignant cells depend on FASN activity for growth and survival. In fact, FASN is overexpressed in a variety of human cancers including cutaneous melanoma, in which its levels of expression are associated with a poor prognosis and depth of invasion. Here, we show that the specific inhibition of FASN activity by the antiobesity drug Orlistat or siRNA is able to significantly reduce proliferation and promote apoptosis in the mouse metastatic melanoma cell line B16-F10. These results prompted us to verify the effect of FASN inhibition on the metastatic process in a model of spontaneous melanoma metastasis, in which B16-F10 cells injected in the peritoneal cavity of C57BL/6 mice metastasize to the mediastinal lymph nodes. We observed that mice treated with Orlistat 48 hr after the inoculation of B16-F10 cells exhibited a 52% reduction in the number of mediastinal lymph node metastases, in comparison with the control animals. These results suggest that FASN activity is essential for B16-F10 melanoma cell proliferation and survival while its inactivation by Orlistat significantly reduces their metastatic spread. The chemical inhibition of FASN activity could have a potential benefit in association with the current chemotherapy for melanoma.

Background Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the exchange of triglycerides for esterified cholesterol between HDL and apoB-lipoproteins. Previous studies suggest that CETP may modify glucose metabolism in patients or cultured cells. In this study, we tested if stable CETP expression would impair glucose metabolism. Methods We used human CETP transgenic mice and non-transgenic littermate controls (NTg), fed with control or high fat diet, as well as in dyslipidemic background and aging conditions. Assays included glucose and insulin tolerance tests, isolated islets insulin secretion, tissue glucose uptake and adipose tissue GLUT mRNA expression. Results CETP expression did not modify glucose or insulin tolerance in all tested conditions such as chow and high fat diet, adult and aged mice, normo and dyslipidemic backgrounds. Fasting and fed state plasma levels of insulin were not differ in CETP and NTg mice. Direct measurements of isolated pancreatic islet insulin secretion rates induced by glucose (11, 16.7 or 22 mM), KCl (40 mM), and leucine (10 mM) were similar in NTg and CETP mice, indicating that CETP expression did not affect β-cell function in vivo and ex vivo. Glucose uptake by insulin target tissues, measured in vivo using 3H-2-deoxyglucose, showed that CETP expression had no effect on the glucose uptake in liver, muscle, perigonadal, perirenal, subcutaneous and brown adipose tissues. Accordingly, GLUT1 and GLUT4 mRNA in adipose tissue were not affected by CETP. Conclusions In summary, by comparing the in vivo all-or-nothing CETP expressing mouse models, we demonstrated that CETP per se has no impact on the glucose tolerance and tissue uptake, global insulin sensitivity and beta cell insulin secretion rates.

Backgrounds The development of effective strategies for the management of overweight in adolescence is a well recognized need. The current study investigates the effectiveness of an e-therapeutic platform (Next.Step) which aims to promote weight management skills and the adoption of health-promoting behaviours among overweight adolescents. Methods We conducted a randomized clinical trial with a sample of 80 adolescents. The control group followed the standard intervention. The experimental group was invited to access the platform during 12 weeks in addition to the standard intervention. Results Although there was no change in the primary outcomes (body mass index and percentage of fat mass), the results suggest that the program is associated with an improvement in the ‘positive perspective of life’ and ‘benefits perceived from the intervention’, which have been identified as relevant factors for an effective weight management. Conclusions Our findings provide little support for the effectiveness of internet-based weight management programs as an add-on to the standard intervention. info:eu-repo/semantics/publishedVersion

Objective: Reliable and valid instruments are essential for understanding health-promoting behaviors in adolescents. This study analyzed the psychometric properties of the Portuguese version of the Adolescent Lifestyle Profile (ALP). Methods: A linguistic and cultural translation of the ALP was conducted with 236 adolescents from two different settings: a community (n = 141) and a clinical setting (n = 95). Internal consistency reliability and confirmatory factor analysis were performed. Results: Results showed an adequate fit to data, yielding a 36-item, seven-factor structure (CMIN/DF = 1.667, CFI = 0.807, GFI = 0.822, RMR = 0.051, RMSEA = 0.053, PNFI = 0.575, PCFI = 0.731). The ALP presented a high internal consistency (α = 0.866), with the subscales presenting moderate reliability values (from 0.492 to 0.747). The highest values were in Interpersonal Relations (3.059 ± 0.523) and Positive Life Perspective (2.985 ± 0.588). Some gender differences were found. Findings showed that adolescents from the clinic reported an overall healthier lifestyle than those from the community setting (2.598 ± 0.379 vs. 2.504 ± 0.346; t = 1.976, p = 0.049). Conclusion: The ALP Portuguese version is a psychometrically reliable, valid, and useful measurement instrument for assessing health-promoting lifestyles in adolescence. The ALP is cross-culturally validated and can decisively contribute to a better understanding of adolescent health promotion needs. Additional research is needed to evaluate the instrument's predictive validity, as well as its clinical relevance for practice and research. Resumo: Objetivo: Os instrumentos confiáveis e válidos são fundamentais para entender os estilos de vida de promoção da saúde de adolescentes. Este estudo analisa as propriedades psicométricas da versão em português do Perfil do Estilo de Vida Adolescente (ALP). Métodos: Foi realizada uma tradução linguística e cultural do ALP com 236 adolescentes de duas configurações diferentes: uma configuração de comunidade (N = 141) e uma clínica (N = 95). Foram realizadas uma análise da confiabilidade da coerência interna e uma análise fatorial confirmatória. Resultados: Os resultados mostraram-se adequados aos dados, gerando uma estrutura de 7 fatores com 36 itens (CMIN/DF = 1,667, IAC = 0,807, GFI = 0,822, RMR = 0,051, RMSEA = 0,053, PNFI = 0,575, PCFI = 0,731). O ALP apresentou grande coerência interna (α = 0,866), com as subescalas apresentando valores de confiabilidade moderados (de 0,492 a 0,747). Os maiores valores foram de Relações Interpessoais (3,059 ± 0,523) e Perspectiva de Vida Positiva (2,985 ± 0,588). Foram encontradas algumas diferenças entre os sexos. Os achados mostraram que os adolescentes da clínica relataram um estilo de vida mais saudável em geral que os da configuração da comunidade (2,598 ± 0,379 em comparação a 2,504 ± 0,346; t = 1,976, p = 0,049). Conclusão: A versão em português do ALP é um instrumento de mensuração psicometricamente confiável, válido e útil para avaliar os estilos de vida de promoção da saúde na adolescência. O ALP é validado em diferentes culturas e pode contribuir de forma decisiva para um melhor entendimento das necessidades de promoção da saúde na adolescência. É necessária uma pesquisa adicional para avaliar a validade preditiva do instrumento, bem como sua relevância clínica para a prática e pesquisa. Keywords: Lifestyle, Adolescents, Instrument validation, Portuguese, Health-promoting, Psychometric, Palavras-chave: Estilo de vida, Adolescentes, Validação instrumental, Português, Promoção da saúde, Psicometria