RESUMO
HDL particles can be structurally modified in atherosclerotic disorders associated with low HDL cholesterol level (HDL-C). We studied whether the lipidome of the main phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) species of HDL2 and HDL3 subfractions is associated with premature coronary heart disease (CHD) or metabolic syndrome (MetS) in families where common low HDL-C predisposes to premature CHD. The lipidome was analyzed by LC-MS. Lysophosphatidylcholines were depleted of linoleic acid relative to more saturated and shorter-chained acids containing species in MetS compared with non-affected subjects: the ratio of palmitic to linoleic acid was elevated by more than 30%. A minor PC (16:0/16:1) was elevated (28-40%) in MetS. The contents of oleic acid containing PCs were elevated relative to linoleic acid containing PCs in MetS; the ratio of PC (16:0/18:1) to PC (16:0/18:2) was elevated by 11-16%. Certain PC and SM ratios, e.g., PC (18:0/20:3) to PC (16:0/18:2) and a minor SM 36:2 to an abundant SM 34:1, were higher (11-36%) in MetS and CHD. The fatty acid composition of certain LPCs and PCs displayed a characteristic pattern in MetS, enriched with palmitic, palmitoleic or oleic acids relative to linoleic acid. Certain PC and SM ratios related consistently to CHD and MetS.
Assuntos
Doença da Artéria Coronariana/metabolismo , Ácidos Graxos/metabolismo , Lipoproteínas HDL/metabolismo , Síndrome Metabólica/metabolismo , Fosfolipídeos/metabolismo , Adulto , Família , Feminino , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: People face varying obstacles when interacting with health information in their everyday lives. OBJECTIVES: This study aims to examine the applicability of a multidimensional Everyday Health Information Literacy (EHIL) screening tool in detecting people with challenges in accessing, understanding, evaluating and using health information in everyday situations. METHODS: Previously collected EHIL screening tool data from Finnish upper secondary school students (n = 217), Finnish young men (n = 1450), Finnish adults with an increased risk for metabolic syndrome (n = 559) and Namibian university students (n = 271) were reanalysed to examine the factorial structure of the tool and to compare the groups. Statistical analyses included exploratory factor analyses, calculation of mean factor scores and one-way analysis of variance. RESULTS: A three factor structure ('awareness', 'access', 'assessment') for the screening tool was supported based on the Finnish samples. However, the Namibian data did not follow a similar structure. Significant differences in groupwise factor scores were discovered. DISCUSSION: The findings suggest that the multidimensional EHIL screening tool can be used in pointing out areas where individuals or groups may need support. CONCLUSION: The tool may be useful to health information and library services workers when counselling or educating the public.
Assuntos
Letramento em Saúde/normas , Programas de Rastreamento/métodos , Adolescente , Análise de Variância , Feminino , Finlândia , Humanos , Competência em Informação , Masculino , Adulto JovemRESUMO
BACKGROUND: Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of FTO genotype in this interaction. METHODS: This study was a field trial of 62 adolescents from boys' high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in peripheral blood mononuclear cells (PBMCs). Anthropometric measurements were assessed at baseline and after 18 weeks of intensive lifestyle intervention. RESULTS: Our results showed that IRX3 expression in the intervention group was significantly up-regulated compared to baseline (P = 0.007) and compared to the control group (P = 0.011).The intervention group had significantly up-regulated transcripts of IRX3 only in rs9930506 risk allele carriers of the intervention group compared to risk allele carriers of the control group (P = 0.017). Moreover, our data showed that the FTO expression was up-regulated in AA genotype carriers and down-regulated in AG/GG genotype carriers (P = 0.017). CONCLUSION: Lifestyle modification may exert its effects on obesity through changes in the expression level of the FTO and IRX3 genes. However, FTO genotype plays a role in the extent of the effect of lifestyle changes on gene expression. Further studies are crucial to have a better understanding of the interaction between lifestyle, genetics and anthropometric measurements. Trial registration This paper reports a comprehensive intervention study (Interactions of Genetics, Lifestyle and Anthropometrics study or IGLA study), which is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( https://www.irct.ir/searchresult.php?id=25699&number=2 ).
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Interação Gene-Ambiente , Proteínas de Homeodomínio/genética , Estilo de Vida , Sobrepeso , Obesidade Infantil , Fatores de Transcrição/genética , Programas de Redução de Peso/métodos , Adolescente , Índice de Massa Corporal , Peso Corporal , Criança , Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico) , Masculino , Sobrepeso/genética , Sobrepeso/terapia , Obesidade Infantil/genética , Obesidade Infantil/terapia , Polimorfismo de Nucleotídeo Único , Comportamento de Redução do Risco , EstudantesRESUMO
AIMS/HYPOTHESIS: Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes. METHODS: A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1) from serum or plasma samples. These ceramides were analysed in a population-based risk factor study (FINRISK 2002, n = 8045), in a cohort of participants undergoing elective coronary angiography for suspected stable angina pectoris (Western Norway Coronary Angiography Cohort [WECAC], n = 3344) and in an intervention trial investigating improved methods of lifestyle modification for individuals at high risk of the metabolic syndrome (Prevent Metabolic Syndrome [PrevMetSyn], n = 371). Diabetes risk score models were developed to estimate the 10 year risk of incident diabetes. RESULTS: Analysis in FINRISK 2002 showed that the Cer(d18:1/18:0)/Cer(d18:1/16:0) ceramide ratio was predictive of incident diabetes (HR per SD 2.23, 95% CI 2.05, 2.42), and remained significant after adjustment for several risk factors, including BMI, fasting glucose and HbA1c (HR 1.34, 95% CI 1.14, 1.57). The finding was validated in the WECAC study (unadjusted HR 1.81, 95% CI 1.53, 2.14; adjusted HR 1.39, 95% CI 1.16, 1.66). In the intervention trial, the ceramide ratio and diabetes risk scores significantly decreased in individuals who had 5% or more weight loss. CONCLUSIONS/INTERPRETATION: The Cer(d18:1/18:0)/Cer(d18:1/16:0) ratio is an independent predictive biomarker for incident diabetes, and may be modulated by lifestyle intervention.
Assuntos
Ceramidas/sangue , Diabetes Mellitus/diagnóstico , Ácido Palmítico/sangue , Ácidos Esteáricos/sangue , Idoso , Angina Pectoris/complicações , Angina Pectoris/diagnóstico , Índice de Massa Corporal , Estudos de Coortes , Angiografia Coronária , Diabetes Mellitus/sangue , Feminino , Finlândia , Humanos , Resistência à Insulina , Masculino , Espectrometria de Massas , Síndrome Metabólica/metabolismo , Noruega , Fatores de Risco , Redução de PesoRESUMO
BACKGROUND: The underlying mechanism of the effect of FTO genotype on body mass index (BMI) and body composition is unknown. The objective of the study was to investigate the association of FTO gene polymorphisms with anthropometric indices in adolescent boys after adjustments for dietary intake and physical activity. METHODS: In this school-based study, we enrolled 123 male adolescents without extra weight and 110 male adolescents with body mass index (BMI) higher than + 1 Z-score. The DNA samples were genotyped for the FTO gene polymorphisms by DNA Sequencing. BMI and body composition were assessed using bioelectrical impedance analyzer scale. Association of the FTO polymorphisms with Weight, height, BMI, body fat percent and skeletal muscle percent were investigated. Data on potential confounders (calorie intake and physical activity) were collected through the use of pre-tested questionnaires. RESULTS: Adolescents with higher BMI and body fat percent and lower skeletal muscle percent were more likely to have a newly found haplotype of rs9930506, rs9930501 & rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) compared with those with the lower BMI (6.15;2.28-16.63), body fat percent (9.54;0.92-47.44) and higher skeletal muscle percent (9.26;1.85-46.38). This association was not changed after controlling for age. Additional adjustments for calorie intake and physical activity did not alter the association. CONCLUSIONS: A haplotype in the first intron of the FTO gene had a strong association with obesity indices in adolescent boys after adjustments for calorie intake and physical activity. It's suggested that the FTO genotype exert its effects on adolescents' anthropometric indices as haplotype and through mechanisms other than changes in calorie intake and expenditure. TRIAL REGISTRATION: This paper reports the first phase of a comprehensive interventional study (Interactions of Genetics, lifestyle and anthropometrics study or IGLA study) and is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( http://www.irct.ir/searchresult.php?id=25699&number=2 ).
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Ingestão de Energia/genética , Exercício Físico/fisiologia , Predisposição Genética para Doença/genética , Haplótipos/genética , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Antropometria/métodos , Composição Corporal/genética , Índice de Massa Corporal , Criança , Estudos Transversais , Humanos , Irã (Geográfico) , Masculino , Estudos RetrospectivosRESUMO
The formation of healthy habits is considered to play a fundamental role in health behavior change. A variety of studies on Health Behavior Change Support Systems (HBCSS) have been conducted recently, in which individuals use such systems to influence their own attitudes or behaviors to achieve their personal goals. However, comparatively much less research has been devoted to studying how the users of these systems form habits with the help of HBCSS, or to understanding how to design these systems to support habit formation. OBJECTIVE: The objective of this article is to study HBCSS user experiences regarding habit formation through an intervention study targeted at establishing a healthier lifestyle. This study also aims to map habit formation stages, as suggested by Lally and Gardner, with the Persuasive System Design (PSD) model. The application domain is the prevention of metabolic syndrome, in which 5% weight loss can significantly reduce the prevalence of the syndrome. METHODS: This study employs a web-based HBCSS named Onnikka, a lifestyle intervention designed for the prevention of metabolic syndrome for participants who are at risk of developing a metabolic syndrome or are already suffering from it. The system under investigation was designed according to the principles of the PSD model and Behavior Change Support System framework. Lally and Gardner's research on the stages of habit formation were used to study the extent to which the Onnikka system was able to enhance the development of new habits. A total of 43 Onnikka users were interviewed for this study during and after a 52-week intervention period. The research approach employed here was hermeneutics, which leans ontologically toward the social construction of reality, gained through language, consciousness, and shared meaning. In addition, the system's login data and participants' weight measurements were utilized to build an interpretation of the results. RESULTS: The findings of this study suggest that IT habits appear to have a strong linkage with use adherence, whereas lifestyle habits did not seem to be directly related to the 5% weight loss among study participants. Moreover, habit formation stages provide a possible explanation for why self-monitoring, reminders, and tunneling were perceived as especially valuable features in this study. CONCLUSIONS: For sustainable weight management, holistic e-health interventions are required, and the PSD model offers a practical approach for designing and developing them. Recognizing the stages of habit formation provides additional valuable guidance for designing systems that help shape an individual's habits.
Assuntos
Hábitos , Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Síndrome Metabólica/prevenção & controle , Educação de Pacientes como Assunto/métodos , Programas de Redução de Peso , Adulto , Algoritmos , Cognição , Aconselhamento , Feminino , Finlândia , Humanos , Internet , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Participação do Paciente , Comunicação Persuasiva , Pesquisa Qualitativa , Software , Adulto JovemRESUMO
Genetic variants in the fat mass- and obesity-associated gene Fto are linked to the onset of obesity in humans. The causal role of the FTO protein in obesity is supported by evidence obtained from transgenic mice; however, the underlying molecular pathways pertaining to the role of FTO in obesity have yet to be established. In this study, we investigate the Fto gene in mouse brown adipose tissue and in the browning process of white adipose tissue. We analyze distinct structural and molecular factors in brown and white fat depots of Fto-deficient mice under normal and obesogenic conditions. We report significant alterations in the morphology of adipose tissue depots and the expression of mRNA and microRNA related to brown adipogenesis and metabolism in Fto-deficient mice. Furthermore, we show that high-fat feeding does not attenuate the browning process of Fto-deficient white adipose tissue as observed in wild-type tissue, suggesting a triggering effect of the FTO pathways by the dietary environment.
Assuntos
Adipogenia/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , MicroRNAs/genética , Obesidade/genética , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato/deficiência , Animais , Biomarcadores/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica , Metabolismo Energético/genética , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Adrenérgicos beta 3/genética , Receptores Adrenérgicos beta 3/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Bile acids play multiple roles in the physiology of vertebrates; they facilitate lipid absorption, serve as signaling molecules to control carbohydrate and lipid metabolism, and provide a disposal route for cholesterol. Unexpectedly, the α-methylacyl-CoA racemase (Amacr) deficient mice, which are unable to complete the peroxisomal cleavage of C27-precursors to the mature C24-bile acids, are physiologically asymptomatic when maintained on a standard laboratory diet. The aim of this study was to uncover the underlying adaptive mechanism with special reference to cholesterol and bile acid metabolism that allows these mice to have a normal life span. Intestinal cholesterol absorption in Amacr-/- mice is decreased resulting in a 2-fold increase in daily cholesterol excretion. Also fecal excretion of bile acids (mainly C27-sterols) is enhanced 3-fold. However, the body cholesterol pool remains unchanged, although Amacr-deficiency accelerates hepatic sterol synthesis 5-fold. Changes in lipoprotein profiles are mainly due to decreased phospholipid transfer protein activity. Thus Amacr-deficient mice provide a unique example of metabolic regulation, which allows them to have a normal lifespan in spite of the disruption of a major metabolic pathway. This metabolic adjustment can be mainly explained by setting cholesterol and bile acid metabolism to a new balanced level in the Amacr-deficient mouse.
Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Racemases e Epimerases/metabolismo , Animais , Ácidos e Sais Biliares/genética , Colesterol/genética , Longevidade/fisiologia , Camundongos , Camundongos Knockout , Racemases e Epimerases/genéticaRESUMO
INTRODUCTION: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. METHODS: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. RESULTS: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. DISCUSSION: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.
Assuntos
Poliaminas Biogênicas/metabolismo , Etanol/toxicidade , Transtornos do Espectro Alcoólico Fetal/etiologia , Retardo do Crescimento Fetal/etiologia , Defeitos do Tubo Neural/etiologia , Animais , Modelos Animais de Doenças , Desenvolvimento Embrionário/efeitos dos fármacos , Etanol/administração & dosagem , Feminino , Transtornos do Espectro Alcoólico Fetal/metabolismo , Transtornos do Espectro Alcoólico Fetal/patologia , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Idade Gestacional , Cabeça , Homeostase/efeitos dos fármacos , Camundongos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/metabolismo , Fenótipo , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Tecidual , Saco Vitelino/efeitos dos fármacos , Saco Vitelino/metabolismoRESUMO
Success in long-term weight management depends partly on psychological and behavioral aspects. Understanding the links between psychological factors and eating behavior tendencies is needed to develop more effective weight management methods. This population-based cross-sectional study examined whether eating self-efficacy (ESE) is associated with cognitive restraint (CR), uncontrolled eating (UE), emotional eating (EE), and binge eating (BE). The hypothesis was that individuals with low ESE have more unfavorable eating behavior tendencies than individuals with high ESE. Participants were classified as low ESE and high ESE by the Weight-Related Self-Efficacy questionnaire (WEL) median cut-off point. Eating behavior tendencies were assessed with Three Factor Eating Questionnaire R-18 and Binge Eating Scale, and additionally, by the number of difficulties in weight management. The difficulties were low CR, high UE, high EE, and moderate or severe BE. Five hundred and thirty-two volunteers with overweight and obesity were included in the study. Participants with low ESE had lower CR (p < 0.03) and higher UE, EE, and BE (p < 0.001) than participants with high ESE. Thirty-nine percent of men with low ESE had at least two difficulties in successful weight control while this percentage was only 8% in men with high ESE. In women, the corresponding figures were 56% and 10%. The risk of low ESE was increased by high UE [OR 5.37 (95% CI 1.99-14.51)], high EE [OR 6.05 (95% CI 2.07-17.66)], or moderate or severe BE [OR 12.31 (95% CI 1.52-99.84)] in men, and by low CR [OR 5.19 (95% CI 2.22-12.18)], high UE [OR 7.20 (95% CI 2.41-19.22)], or high EE [OR 23.66 (95% CI 4.79-116.77)] in women. Low ESE was associated with unfavorable eating behavior tendencies and multiple concomitant difficulties in successful weight loss promotion. These eating behavior tendencies should be considered when counseling patients with overweight and obesity.
Assuntos
Sobrepeso , Autoeficácia , Masculino , Humanos , Feminino , Sobrepeso/psicologia , Estudos Transversais , Comportamento Alimentar/psicologia , Obesidade/psicologia , Inquéritos e QuestionáriosRESUMO
We conducted a clinical trial with 22 healthy volunteers to investigate the effects of pregnane X receptor (PXR) agonist rifampin on blood pressure (BP). The study was randomized, crossover, single-blind, and placebo-controlled. Rifampin 600 mg or placebo once daily was administered for a week and the 24-hour ambulatory BP was monitored at the end of each arm on the eighth day. Rifampin elevated the mean systolic and diastolic 24-hour BP (4.7 mmHg, P < 0.0001, and 3.0 mmHg, P < 0.001, respectively) as well as the mean heart rate (3.5 bpm, P = 0.038). The serum renin concentration and the plasma renin activity were increased. Although rifampin increased circulating 4ß-hydroxycholesterol (4ßHC) as expected, the plasma 4ßHC concentration strongly negatively correlated with 24-hour BP, especially systolic, in both rifampin and placebo arms (rifampin systolic BP, r = -0.69, P < 0.001; placebo systolic BP, r = -0.70, P < 0.001). The 4ßHC, an agonist for liver X receptor (LXR), induced renin expression modestly in LXR-α expressing Calu-6 cells but only at unphysiologically high 4ßHC concentrations. In conclusion, rifampin stimulates renin activity and has a hypertensive effect. This finding should be considered when designing interaction studies involving rifampin or other PXR agonists. Furthermore, PXR may represent a putative therapeutic target for the treatment of hypertension.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Receptor de Pregnano X/agonistas , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/sangue , Rifampina/administração & dosagem , Adulto , Biomarcadores/sangue , Linhagem Celular Tumoral , Estudos Cross-Over , Feminino , Finlândia , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidroxicolesteróis/sangue , Receptores X do Fígado/metabolismo , Masculino , Receptor de Pregnano X/metabolismo , Renina/genética , Método Simples-Cego , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: The aim was to investigate whether lifestyle changes produced by persuasive Information and Communication Technology (ICT) counselling can lower the prevalence of metabolic syndrome (MetS). METHODS: A total of 532 participants (20-60 years, body mass index 27-35 kg/m2) were randomly assigned to six arms according to counselling type (no, short-term, or intensive) with or without ICT intervention. In this report the prevalence of MetS and its components were compared between no-ICT group and ICT group. Moreover, the frequency of the web information system usage was analysed for the number of logins, responses to weekly messages, and other record variables. RESULTS: The ICT group had significantly lower proportion of MetS (33.7% vs. 45.3%, p = .022) than the no-ICT group at 2-year follow-up. In mixed model, the ICT group had lower prevalence of MetS than no-ICT group (OR 0.50, 95%CI 0.27-0.90) after intervention. The tertile with the highest utilization had 71% lower prevalence of MetS compared with the lowest utilization tertile or the no-ICT group. CONCLUSIONS: Web-based ICT is able to reduce the prevalence of MetS. In addition, higher utilization of the web information system is associated with a greater decrease in the prevalence of MetS. Key messages Our internet health behaviour change support system based on persuasive design and cognitive behaviour therapy markedly reduces metabolic syndrome in overweight/obese subjects. As a stand-alone tool it may save healthcare personnel resources as it is suitable at a low cost for both obese/overweight patients and the public at large.
Assuntos
Aconselhamento/métodos , Estilo de Vida Saudável , Síndrome Metabólica/prevenção & controle , Obesidade/psicologia , Adulto , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Grupos de AutoajudaRESUMO
Activation of pregnane X receptor (PXR) elevates circulating 4ß-hydroxycholesterol (4ßHC), an agonist of liver X receptor (LXR). PXR may also regulate 25-hydroxycholesterol and 27-hydroxycholesterol. Our aim was to elucidate the roles of PXR and oxysterols in the regulation of cholesterol transporters. We measured oxysterols in serum of volunteers dosed with PXR agonist rifampicin 600 mg/day versus placebo for a week and analyzed the expression of cholesterol transporters in mononuclear cells. The effect of 4ßHC on the transport of cholesterol and the expression of cholesterol transporters was studied in human primary monocyte-derived macrophages and foam cells in vitro. The expression of cholesterol transporters was measured also in rat tissues after dosing with a PXR agonist. The levels of 4ßHC were elevated, while 25-hydroxycholesterol and 27-hydroxycholesterol remained unchanged in volunteers dosed with rifampicin. The expression of ATP binding cassette transporter A1 (ABCA1) was induced in human mononuclear cells in vivo. The influx of cholesterol was repressed by 4ßHC, as was the expression of influx transporter lectin-like oxidized LDL receptor-1 in vitro. The cholesterol efflux and the expression of efflux transporters ABCA1 and ABCG1 were induced. The expression of inducible degrader of the LDL receptor was induced. In rats, PXR agonist increased circulating 4ßHC and expression of LXR targets in peripheral tissues, especially ABCA1 and ABCG1 in heart. In conclusion, PXR activation-elevated 4ßHC is a signaling molecule that represses cholesterol influx and induces efflux. The PXR-4ßHC-LXR pathway could link the hepatic xenobiotic exposure and the regulation of cholesterol transport in peripheral tissues.
RESUMO
The role of FTO genotype in the effect of FTO gene expression level on change in body mass index and body composition has not been studied. This study aimed to investigate the role of FTO genotype in the association between change in the expression level of the FTO gene with changes in anthropometric measurements in obese and overweight adolescent boys. Eighty-four boys aged 12 to 16 years participated in this longitudinal study. A bioimpedance analyzer (BIA) was used to estimate percentage of body fat (%body fat) and percentage of skeletal muscle (%skeletal muscle). The FTO gene expression level in peripheral blood mononuclear cells (PBMCs) was assessed using quantitative Real Time PCR (qPCR). The DNA samples were genotyped for the FTO gene polymorphisms by DNA sequencing. All measurements were performed at baseline and after intervention. A significant association was observed between the level of gene expression and %skeletal muscle. The gene expression fold change was significantly associated with change in %skeletal muscle in AA or AG genotype carriers (ß = 0.34, p = .02). No significant association was detected between the change in FTO gene expression with change in anthropometric indices in GG genotype carriers. In conclusion, the association between FTO gene expression and body composition can be influenced by FTO genotype. Future studies are required to assess the interactions between FTO genotype, FTO gene expression in different tissues, and body composition.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Regulação da Expressão Gênica , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Adolescente , Antropometria , Composição Corporal/genética , Índice de Massa Corporal , Criança , Estudos de Coortes , Genótipo , Humanos , Incidência , Modelos Lineares , Estudos Longitudinais , Masculino , Sobrepeso/epidemiologia , Sobrepeso/genética , Papel (figurativo) , Estados UnidosRESUMO
This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients' intake were assessed at baseline and after 18 weeks of the intervention. The results identified that the higher carbohydrates intake significantly up-regulated the FTO gene (P = 0.001) and down-regulated the IRX3 gene (P = 0.01). Protein intake up-regulated the FTO gene (P = 0.001). In carriers of GG genotype of FTO gene, the amount of dietary carbohydrate had a positive association with FTO gene expression (p = 0.001, and p = 0.04, respectively). In AA/AG carriers, dietary protein was positively associated with FTO gene expression (p = 0.001) and dietary carbohydrate was negatively associated with IRX3 gene expression (P = 0.04). Therefore, dietary carbohydrateseems to be associated with FTO and IRX3 genes expression. These associations are influenced by FTO genotype.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Carboidratos da Dieta/administração & dosagem , Proteínas de Homeodomínio/genética , Obesidade/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adolescente , Carboidratos da Dieta/farmacologia , Regulação para Baixo , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico) , Estudos Longitudinais , Masculino , Regulação para CimaRESUMO
INTRODUCTION: The modifying effect of FTO gene expression level on change in body mass index and body composition has not been studied before. This study aimed to investigate the association between change in the expression level of the FTO gene and changes in anthropometric measurements in obese and overweight adolescent boys. MATERIAL AND METHODS: Eighty-four boys aged 12 to 16 years participated in this longitudinal study. A Bio Impedance Analyzer (BIA) was used to estimate percentage of body fat (%BF) and percentage of skeletal muscle (%SM). The FTO gene expression level in peripheral blood mononuclear cells was assessed using quantitative real-time PCR (qPCR). All measurements were performed at baseline and after 18 weeks. RESULTS: After 18 weeks, mean weight was reduced by 2.39 kg, body mass index by 0.09 kg/m2, %BF by 0.82% and %SM increased by 0.44%. Moreover, the level of FTO gene expression increased 0.42-fold higher than baseline. The change in expression level of the FTO gene was positively associated with change in %SM (ß = 0.31, p = 0.02). CONCLUSIONS: FTO gene expression change was associated with change in %SM in male adolescents. Future studies are required to assess the interactions between FTO gene expression in different tissues and body composition.
RESUMO
BACKGROUND: Single-nucleotide polymorphisms (SNPs), which are located in the first intron of the FTO gene, are reported to be associated with body weight and the body mass index (BMI). However, their effects on anthropometric measurements in adolescents are poorly understood. OBJECTIVE: This study aimed to investigate the association of three adjacent polymorphisms (rs9930506, rs9930501, & rs9932754) in the FTO gene with anthropometric indices in Iranian adolescent males. DESIGN: The participants comprised a total of 237 adolescent males who were recruited randomly from two high schools in Tehran, Iran. The DNA samples were genotyped for the FTO gene polymorphisms by DNA sequencing. BMI, body fat percentage (BF%), and body muscle percentage (BM%) were determined using a validated bioelectrical impedance analysis scale. The association of the FTO polymorphisms with weight, height, BMI, BF%, and BM% was investigated. RESULTS: A haplotype of rs9930506, rs9930501, and rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) was found to be significantly associated with higher weight (OR = 1.32), BMI (OR = 5.36) and BF% (OR = 1.46), and lower BM% (OR = 3.59) (all P<0.001). None of the students with GGC genotypes were underweight, while all of the students with AAT genotypes had high muscle mass. CONCLUSIONS: A haplotype in the first intron of the FTO gene had a strong association with obesity indices in Iranian adolescent males. The FTO gene polymorphisms might have greater effects on anthropometric indices than what was previously imagined. Moreover, we suggested that the FTO gene exerted their effects on anthropometric measurements through haplotypes (and not single SNPs).
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Composição Corporal/genética , Índice de Massa Corporal , Polimorfismo de Nucleotídeo Único , Adolescente , Criança , Estudos Transversais , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Íntrons , Irã (Geográfico) , Masculino , Obesidade/genética , Análise de Sequência de DNA , Magreza/genéticaRESUMO
OBJECTIVE: The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. METHODS: HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. RESULTS: While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001). CONCLUSION: Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.
Assuntos
HDL-Colesterol/sangue , Doença da Artéria Coronariana/epidemiologia , Lipoproteínas HDL/sangue , Síndrome Metabólica/epidemiologia , Adulto , Idade de Início , Idoso , Doença da Artéria Coronariana/sangue , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p = 0.001), and 76.1 (48.2) for NoDR (p = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p > 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.
Assuntos
Autoanticorpos/sangue , Retinopatia Diabética/imunologia , Imunoglobulina A/sangue , Lipoproteínas LDL/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Retinopatia Diabética/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Obesity has become a severe health problem in the world. Even a moderate 5% weight loss can significantly reduce the prevalence of metabolic syndrome, which can be vital for preventing comorbidities caused by the obesity. Health Behavior Change Support Systems (hBCSS) emphasize an autogenous approach, where an individual uses the system to influence one's own attitude or behavior to achieve his or her own goal. Regardless of promising results, such health interventions technology has often been considered merely as a tool for delivering content that has no effect or value of its own. More research on actual system features is required. OBJECTIVES: The objective of this study is to describe how users perceive persuasive software features designed and implemented into a support system. METHODS: The research medium in this study is a web-based information system designed as a lifestyle intervention for participants who are at risk of developing a metabolic syndrome or who are already suffering from it. The system was designed closely following the principles of the Persuasive Systems Design (PSD) model and the Behavior Change Support Systems (BCSS) framework. A total of 43 system users were interviewed for this study during and after a 52 week intervention period. In addition, the system's login data and subjects' Body Mass Index (BMI) measures were used to interpret the results. RESULTS: This study explains in detail how the users perceived using the system and its persuasive features. Self-monitoring, reminders, and tunneling were perceived as especially beneficial persuasive features. The need for social support appeared to grow along the duration of the intervention. Unobtrusiveness was found to be very important in all stages of the intervention rather than only at the beginning. CONCLUSIONS: Persuasive software features have power to affect individuals' health behaviors. Through their systematicity the PSD model and the BCSS framework provide effective support for the design and development of technological health interventions. Designers of such systems may choose, for instance, to implement more self-monitoring tools to help individuals to adjust their personal goals with the system's offerings better.