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1.
Georgian Med News ; (292-293): 49-53, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31560662

RESUMO

The aim of this article is to describe the current level of knowledge about the relationship between overweight and genomic instability. The relationship between overweight / obesity and cancer has been well studied in numerous studies. A feature of overweight and obesity is the formation of reactive oxygen species and cytokines, which lead to damage to the genetic material of the cell. The review article analyzes literary sources, which condemn the data on the methods used in research concerning the links between genomic instability and obesity. Analyzed studies on the stability of DNA in humans and animals with overweight and obesity.


Assuntos
Dano ao DNA , Instabilidade Genômica , Obesidade/genética , Sobrepeso/genética , Animais , Índice de Massa Corporal , Humanos
2.
Nat Med ; 25(9): 1385-1389, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501613

RESUMO

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.


Assuntos
Envelhecimento/metabolismo , Peso Corporal/genética , Obesidade/metabolismo , Ganho de Peso/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adolescente , Adulto , Envelhecimento/genética , Envelhecimento/patologia , Peso Corporal/fisiologia , Radioisótopos de Carbono/química , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Masculino , Obesidade/genética , Obesidade/patologia , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/patologia , Triglicerídeos/metabolismo , Perda de Peso/genética
3.
Arch Endocrinol Metab ; 63(4): 402-410, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365628

RESUMO

OBJECTIVE: The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. SUBJECTS AND METHODS: The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. RESULTS: The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). CONCLUSIONS: We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.


Assuntos
Obesidade/genética , Sobrepeso/genética , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Adulto , Distribuição por Idade , Angiotensinogênio/genética , Pressão Sanguínea , Índice de Massa Corporal , Brasil , Estudos Transversais , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Distribuição por Sexo , Circunferência da Cintura
4.
Medicine (Baltimore) ; 98(28): e16414, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305457

RESUMO

The gestational weight gain is determined by food habits, environmental and genetic factors.The aims of this paper were to establish relationships between maternal gene polymorphisms (patatin-like phospholipase domain-containing protein 3 rs738409 [PNPLA3 rs738409], glucokinase regulatory protein rs780094 [GCKR rs780094], and guanine nucleotide-binding protein rs5443 [GNB3 rs5443]) and mothers' gestational weight gain, but also neonatal outcomes (birth weight, length, and ponderal index [PI]).We performed a cross-sectional study in a sample of 158 mothers and their product of conception' in an Obstetrics-Gynecology Clinic from Romania. We divided the pregnant women according to the Institute of Medicine recommendations into 3 subgroups: (1) insufficient gestational weight gain; (2) normal gestational weight gain; and (3) excessive gestational weight gain.The gestational weight gain among pregnant women included in this study was classified as insufficient (10.1%), normal (31%), and excessive (58.9%). We found a tendency towards statistical significance for mothers that were overweight or obese before pregnancy to present an excessive gestational weight gain as compared to the normal weight ones. Similarly, we identified a tendency for statistical significance regarding the association between the variant genotype of GNB3 rs5443 and excessive gestational weight gain. We noticed differences that tended to be statistical significant concerning aspartate aminotransferase values between the 3 subgroups, mothers with excessive gestational weight gain having higher values than mothers with normal gestational weight gain (median, IQR: 22.89[17.53; 31.59] for mothers with excessive gestational weight gain versus 22.71[18.58; 27.37] for mothers with normal gestational weight gain). In mothers with excessive gestational weight gain, we found a significant association between the variant genotype of PNPLA3 rs738409 polymorphism and neonatal PI noticing a decrease of this index in case of newborns from mothers carrying the variant genotype.Excessive gestational weight gain was noticed in pregnant women that were obese and overweight before pregnancy. We found a positive association between the variant genotype of GNB3 rs5443 polymorphism and excessive gestational weight gain. Similarly, the presence of variant genotype of PNPLA3 rs738409 in mothers was associated with a lower PI in their newborns. Our study pointed out the most important factors that influence gestational weight gain and related birth outcomes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Desenvolvimento Infantil , Ganho de Peso na Gestação/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética , Lipase/genética , Proteínas de Membrana/genética , Adolescente , Adulto , Peso ao Nascer , Estatura , Estudos Transversais , Feminino , Estudos de Associação Genética , Humanos , Recém-Nascido , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/genética , Adulto Jovem
5.
J Anim Breed Genet ; 136(5): 351-361, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31037768

RESUMO

The plasma very low-density lipoprotein (VLDL) concentration is an effective blood biochemical indicator that could be used to select lean chicken lines. In the current study, we used Genome-wide association study (GWAS) method to detect SNPs with significant effects on plasma VLDL concentration. As a result, 38 SNPs significantly associated with plasma VLDL concentration were identified using at least one of the three mixed linear model (MLM) packages, including GRAMMAR, EMMAX and GEMMA. Nearly, all these SNPs with significant effects on plasma VLDL concentration (except Gga_rs16160897) have significantly different allele frequencies between lean and fat lines. The 1-Mb regions surrounding these 38 SNPs were extracted, and twelve important regions were obtained after combining the overlaps. A total of 122 genes in these twelve important regions were detected. Among these genes, LRRK2, ABCD2, TLR4, E2F1, SUGP1, NCAN, KLF2 and RAB8A were identified as important genes for plasma VLDL concentration based on their basic functions. The results of this study may supply useful information to select lean chicken lines.


Assuntos
Galinhas/genética , Estudo de Associação Genômica Ampla , Lipoproteínas VLDL/sangue , Animais , Doenças das Aves/sangue , Doenças das Aves/genética , Galinhas/sangue , Frequência do Gene , Sobrepeso/sangue , Sobrepeso/genética , Sobrepeso/veterinária , Polimorfismo de Nucleotídeo Único
6.
J Med Food ; 22(5): 499-507, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30990731

RESUMO

A previous genome-wide association study (GWAS) on obese/overweight Korean women reported five new genetic loci associated with the basal metabolic rate (BMR) and body mass index (BMI), NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17. This metabolite GWAS (mGWAS) aimed to identify the key metabolites and metabolic pathways regulated by these genes. Potential metabolic pathways associated with leanness and obesity were identified by detecting metabolites in association with GWAS. Waist circumference, lean body mass, and body fat mass were strongly associated with BMI rather than BMR. However, plasma triglyceride and total cholesterol were significantly higher in obese individuals with low BMR than in lean individuals with high BMR. Upon analyzing NRG3, BCL2L2-PABPN1, and SLC22A17, uric acid, succinic acid, arginine, uridine, and aspartic acid were the metabolites positively associated with obesity. Uric acid and arginine were both identified through general metabolomics targeting of obesity genes classified on the basis of BMI or BMR. Metabolites associated with disruption in beta-oxidation, lipid metabolism, branched-chain amino acid and aromatic amino acid catabolism, the urea cycle, and purine/pyrimidine metabolism play important roles in obesity classified on the basis of either BMI or BMR in middle-aged Korean women. These results further the current understanding of obesity and the predictability of obesity-related risks using mGWAS.


Assuntos
Metabolismo Basal , Obesidade/genética , Obesidade/metabolismo , Sobrepeso/genética , Sobrepeso/metabolismo , Adulto , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Composição Corporal , Índice de Massa Corporal , Feminino , Estudo de Associação Genômica Ampla , Humanos , Metabolismo dos Lipídeos , Metabolômica , Pessoa de Meia-Idade , Circunferência da Cintura
7.
Int J Mol Sci ; 20(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018503

RESUMO

Obesity is a well-described risk factor resulting in premature aging of the cardiovascular system ultimately limiting longevity. Premature cardiac death and aging is the hallmark of Hutchinson-Gilford syndrome (HGPS), a disease caused by defined mutations in the lamin A gene leading to a shortened prelamin A protein known as progerin. Since small amounts of progerin are expressed in healthy individuals we aimed to investigate the association of Body-Mass-Index (BMI) with respect to expression of progerin mRNA in blood samples of patient with known cardiovascular disease. In this cross-sectional retrospective analysis, 111 patients were consecutively included of which 46 were normal (BMI < 25 kg/m2) and 65 overweight (BMI ≥ 25.0 kg/m2). Blood samples were analyzed for quantitative expression of progerin mRNA. Progerin as well as high-sensitive C-Reactive Protein (hs-CRP) levels were significantly upregulated in the overweight group. Linear regression analyses showed a significant positive correlation of BMI and progerin mRNA (n = 111; r = 0.265, p = 0.005), as well as for hs-CRP (n = 110; r = 0.300, p = 0.001) and for Hb1Ac (n = 110; r = 0.336, p = 0.0003). Our data suggest that BMI strongly correlates with progerin mRNA expression and inflammation. Progerin might contribute to well described accelerated biologic aging in obese individuals.


Assuntos
Lamina Tipo A/genética , Sobrepeso/genética , RNA Mensageiro/genética , Regulação para Cima , Adulto , Idoso , Senilidade Prematura/sangue , Senilidade Prematura/genética , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , RNA Mensageiro/sangue , Estudos Retrospectivos
8.
BMC Public Health ; 19(1): 310, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876469

RESUMO

BACKGROUND: The nutrigenomics, overweight/obesity and weight management trial (NOW Trial) is a pragmatic randomized controlled trial of community-dwelling adults recruited from the Group Lifestyle Balance™ (GLB™) Program. The GLB™ Program (formerly referred to as the Diabetes Prevention Program) is an evidence-based, intensive weight management program, which was offered to overweight/obese patients (BMI ≥ 25.0 kg/m2) in a rural Ontario community. METHODS: Patients enrolled in the GLB™ Program were invited to participate in this study. GLB™ groups were randomized 1:1 to receive either the standard GLB™ program + population-based lifestyle advice for weight management, or a modified GLB™ program + personalized, genetic-based lifestyle advice for weight management. The purpose of this study is to determine if the provision of genetic-based lifestyle guidelines is superior to the provision of population-based guidelines in a pragmatic clinical setting to promote changes in: body composition, weight, body mass index, dietary and physical activity habits, as well as attitudes, subjective norms, and behavioural control. The 12-month intervention protocol consists of 23 group-based sessions and 4 one-on-one sessions. Data collection time points include baseline in addition to 3, 6, and 12-month follow up. The comprehensive study design is described in the present manuscript, using both the extended CONSORT checklist for reporting pragmatic trials and the SPIRIT checklist as guidance during manuscript development. DISCUSSION: Overall, this study seeks to pragmatically determine if the provision of DNA-based lifestyle advice leads to improved health and lifestyle outcomes compared to the provision of standard, population-based lifestyle advice. The results of this trial can be used to inform clinical and community nutrition practice guidelines. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov : NCT03015012 on January 9, 2017.


Assuntos
Aconselhamento Genético , Estilo de Vida , Nutrigenômica , Sobrepeso/prevenção & controle , Programas de Redução de Peso , Adulto , Humanos , Obesidade/genética , Obesidade/prevenção & controle , Ontário , Sobrepeso/genética , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa , População Rural/estatística & dados numéricos
9.
Gene ; 699: 88-93, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30858138

RESUMO

The new technologies for data analysis, such as decision tree learning, may help to predict the risk of developing diseases. The aim of the present work was to develop a pilot decision tree learning to predict overweight/obesity based on the combination of six single nucleotide polymorphisms (SNP) located in feeding-associated genes. Genotype study was performed in 151 healthy individuals, who were anonymized and randomly selected from the TALAVERA study. The decision tree analysis was performed using the R package rpart. The learning process was stopped when 15 or less observation was found in a node. The participant group consisted of 78 men and 73 women, who 100 individuals showed body mass index (BMI) ≥ 25 kg/m2 and 51 BMI < 25 kg/m2. Chi-square analysis revealed that individuals with BMI ≥ 25 kg/m2 showed higher frequency of the allelic variation Ala67Ala in AgRP rs5030980 with respect to those with BMI <25 kg/m2. However, the variant Thr67Ala in AgRP rs5030980 was the most frequently found in individuals with BMI <25 kg/m2. There were no statistical differences in the other analyzed SNPs. Decision tree learning revealed that carriers of the allelic variants AgRP (rs5030980) Ala67Ala, ADRB2 (rs1042714) Gln27Glu or Glu27Glu, INSIG2 (rs7566605) 73 + 9802 with CC or GG genotypes and PPARG (rs1801282) with the allelic variants of Ala12Ala or Pro12Pro, will most likely develop overweight/obesity (BMI ≥ 25 kg/m2). Moreover, the decision tree learning indicated that age and gender may change the developed three decision learning associated with overweight/obesity development. The present work should be considered as a pilot demonstrative study to reinforce the broad field of application of new data analysis technologies, such as decision tree learning, as useful tools for diseases prediction. This technology may achieve a potential applicability in the design of early strategies to prevent overweight/obesity.


Assuntos
Obesidade/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Índice de Massa Corporal , Árvores de Decisões , Feminino , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , PPAR gama/genética , Projetos Piloto , Receptores Adrenérgicos beta 2/genética
10.
Gene ; 692: 54-59, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30641221

RESUMO

OBJECTIVE: Obesity is one of the major health problems strongly influenced by lifestyle, genetic and environmental factors. Previous studies have reported many single-nucleotide polymorphisms (SNPs) are associated with obesity in different races. This study aimed to explore the genetic associations between LEPR, MC4R polymorphisms and overweight/obesity in Chinese Han adolescents. METHODS: 400 adolescents including 222 health controls and 178 overweight/obese adolescents were genotyped and their body compositions were also analyzed in this study. RESULTS: We found that allelic and genotypic frequencies of LEPR SNP rs8179183 were significantly different between controls and cases (allelic frequency p < 0.001; genotypic frequency p = 0.004). These difference was still significant (allelic frequency p < 0.011; genotypic frequency p = 0.024) after Bonferroni correction. Moreover, we found that rs8179183 was associated with serum triglyceride level after adjusting for age and body mass index (BMI) (p = 0.037). CONCLUSION: In summary, our results found a significant association between LEPR SNP rs8179183 and overweight/obesity in Chinese Han adolescent. This study may provide a reference for future studies of obesity.


Assuntos
Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética , Receptores para Leptina/genética , Adolescente , Apolipoproteína A-I/sangue , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Insulina/sangue , Masculino , Obesidade/genética , Triglicerídeos/sangue , Triglicerídeos/genética
11.
Obes Facts ; 11(6): 524-533, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30580338

RESUMO

OBJECTIVES: Activation of ß3-adrenoceptor (ADRB3) is essential in the process of human adipose tissue browning, but obese subjects suffered from reduced ability of brown adipose tissue activation. The present study aims to detect the adipocyte ADRB3 expression in overweight individuals and the relationship between adipocyte ADRB3 expression and adiposity in adults. METHODS: Visceral adipose tissue samples were obtained from 85 subjects who underwent abdominal surgery. ADRB3 mRNA and protein expression levels in mature adipocytes and adipose tissue stromal vascular cells were examined by quantitative real-time PCR and Western blot assay, respectively. UCP-1mRNA expression levels in mature adipocytes were examined by quantitative real-time PCR. RESULTS: The data revealed that ADRB3 mRNA (p = 0.021) and protein (p = 0.025) expression levels in mature adipocytes were significantly higher in the normal-weight than in the overweight group. Similar results were also found for ADRB3 mRNA (p = 0.041) and protein (p = 0.025) expressions of stromal vascular cells. An inverse correlation was verified between mature adipocyte ADRB3 mRNA expression and BMI (r = -0.362, p = 0.012). UCP-1 mRNA expression levels in mature adipocytes were higher in the normal-weight group compared with the overweight group (p = 0.045). CONCLUSION: Adipocyte ADRB3 expression levels were down-regulated before the onset of obesity, which indicated that the reduction of ADRB3 expression might be the cause of compromised adipose tissue browning and obesity rather than the result. Thus, the interference of the ADRB3 pathway in adipocytes may provide a potential treatment target for obesity.


Assuntos
Adipócitos/metabolismo , Sobrepeso/genética , Receptores Adrenérgicos beta 3/genética , Tecido Adiposo/metabolismo , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Células Cultivadas , Regulação para Baixo/genética , Feminino , Humanos , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Obesidade/genética , Obesidade/metabolismo , Sobrepeso/etnologia , Sobrepeso/metabolismo , Cultura Primária de Células , Receptores Adrenérgicos beta 3/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Adulto Jovem
12.
Ann Hum Biol ; 45(6-8): 496-505, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30590963

RESUMO

BACKGROUND: The association of the variant rs6265 (G>A) in the brain-derived neurotrophic factor (BDNF) gene with obesity and other obesity-related parameters is not known for the Pakistani population. Moreover, the effects of interaction between BDNF rs6265 and overweight/obesity on obesity-related traits have never been investigated before. AIM: To find the association of the BDNF rs6265 with obesity and related traits and to explore the effect of rs6265 × obesity interaction on obesity-related traits in Pakistanis. SUBJECTS AND METHODS: The study involved a total of 606 subjects, including 306 overweight and obese (OW/OB) cases and 300 normal weight (NW) controls. The genotyping of the BDNF rs6265 was done and obesity-related anthropometric, physical, behavioural and metabolic parameters were determined. Statistical analyses using SPSS software were performed to find the associations. RESULTS: The study revealed a lack of association of the BDNF rs6265 with obesity and obesity-related traits. On the other hand, the interaction between the BDNF rs6265 and overweight/obesity was found to be significantly associated with some of the obesity-related anomalous traits. However, no association between rs6265 and these anomalous traits was seen in either group when the association test was performed in NW and OW/OB groups separately. CONCLUSION: The BDNF rs6265, in the presence of obesity, may be associated with elevated risk of anomalous metabolic, behavioural and physical traits and obesity-related co-morbidities, but it needs to be validated in a significantly larger Pakistani sample population.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Sobrepeso/epidemiologia , Adolescente , Adulto , Antropometria , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/genética , Sobrepeso/genética , Paquistão , Adulto Jovem
13.
Gene ; 679: 126-132, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30176316

RESUMO

Malfunction of apoptosis plays a key role in carcinogenesis. Previous studies have reported that polymorphisms in caspase genes could lead to poor apoptotic signaling, thus facilitating the onset of several human cancers. The aim of this study was to evaluate the association between three polymorphisms (rs1049216, rs2705897 and rs4647603) of the CASP3 gene and the risk of prostate cancer (PCa) in Galicia (NW Spain).The relationship between these single nucleotide polymorphisms (SNPs) and PCa in European populations has yet to be studied. To test this hypothesis, we carried out a case-control study on a total of 243 patients with PCa and 191 healthy individuals, genotyping all polymorphisms using the matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) method. Overall, none of the polymorphisms were clearly associated with the risk of PCa. Nevertheless, the results drawn from this study suggest that genetic variability in the CASP3 gene, in combination with lifestyle and environmental factors may influence the predisposition to develop PCa in the Galician population. Specifically, the results of study seem to hint at a higher risk of PCa in smokers of up to 20 pack-years (PY) and carriers of both the CASP3-rs1049216 GG genotype and the G allele (OR = 3.61, p = 0.044; OR = 1.71; p = 0.018). In addition, the GG and AG genotypes showed increased predisposition to PCa in overweight individuals (OR = 4.43, p = 0.040; OR = 2.00; p = 0.022). Finally, the CASP3-rs4647603 CT genotype and T allele were associated with a higher susceptibility to PCa in obese individuals (ORCT/TT = 4.30, p = 0.003; ORT/C = 3.58, p = 0.004). Further replication studies in other populations are required to assess these findings.


Assuntos
Caspase 3/genética , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Fumar/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Comorbidade , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
14.
Mutat Res ; 777: 64-91, 2018 Jul - Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30115431

RESUMO

Health authorities are alarmed worldwide about the increase of obesity and overweight in the last decades which lead to adverse health effects including inflammation, cancer, accelerated aging and infertility. We evaluated the state of knowledge concerning the impact of elevated body mass on genomic instability. Results of investigations with humans (39 studies) in which DNA damage was monitored in lymphocytes and sperm cells, are conflicting and probably as a consequence of heterogeneous study designs and confounding factors (e.g. uncontrolled intake of vitamins and minerals and consumption of different food types). Results of animal studies with defined diets (23 studies) are more consistent and show that excess body fat causes DNA damage in multiple organs including brain, liver, colon and testes. Different molecular mechanisms may cause genetic instability in overweight/obese individuals. ROS formation and lipid peroxidation were found in several investigations and may be caused by increased insulin, fatty acid and glucose levels or indirectly via inflammation. Also reduced DNA repair and formation of advanced glycation end products may play a role but more data are required to draw firm conclusions. Reduction of telomere lengths and hormonal imbalances are characteristic for overweight/obesity but the former effects are delayed and moderate and hormonal effects were not investigated in regard to genomic instability in obese individuals. Increased BMI values affect also the activities of drug metabolizing enzymes which activate/detoxify genotoxic carcinogens, but no studies concerning the impact of these alterations of DNA damage in obese individuals are available. Overall, the knowledge concerning the impact of increased body weight and DNA damage is poor and further research is warranted to shed light on this important issue.


Assuntos
Instabilidade Genômica , Obesidade/genética , Sobrepeso/genética , Animais , Dano ao DNA , Hormônios Esteroides Gonadais/metabolismo , Humanos , Peroxidação de Lipídeos , Telômero
15.
Nutr Hosp ; 35(4): 957-961, 2018 Aug 02.
Artigo em Espanhol | MEDLINE | ID: mdl-30070888

RESUMO

INTRODUCTION: the histological alteration in the small intestine of the celiac patients produces a poor absorption that deteriorates or hinder an optimal weight gain. This can be the result of an increase expression of the Th17 gluten-specific interleukins. OBJECTIVE: the aim of this study was to compare the expression of Th17 interleukins in celiac patients with normal and overweight/obese nutritional status. METHODS: a total of 22 patients with newly diagnosed celiac disease were eligible: 15 patients with normal weight and seven overweight/obese. Small intestine biopsies were taken for the evaluation of the expression of interleukins through real-time PCR. RESULTS: expression levels of Th17 interleukins showed a tendency to be higher in intestinal biopsies of overweight/obese patients compared to normal weight celiac subjects; however, this difference was not statistical significant. CONCLUSION: body weight excess in celiac patients is not influenced by the expression levels of Th17 interleukins.


Assuntos
Doença Celíaca/complicações , Doença Celíaca/genética , Interleucinas/genética , Interleucinas/metabolismo , Obesidade/genética , Sobrepeso/genética , Células Th17/metabolismo , Adulto , Doença Celíaca/patologia , Feminino , Humanos , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Obesidade/etiologia , Sobrepeso/etiologia
16.
Nutr. hosp ; 35(4): 957-961, jul.-ago. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-179892

RESUMO

Introducción: la alteración histológica en el intestino delgado de los enfermos celiacos produce una pobre absorción que deteriora o dificulta una ganancia óptima de peso. Esto puede ser el resultado de un aumento de la expresión de las interleuquinas Th17 gluten-específicas. Objetivo: el objetivo de este estudio fue comparar la expresión de las interleuquinas Th17 en pacientes celiacos con peso normal y sobrepeso/ obesidad. Métodos: se estudiaron 22 pacientes con reciente diagnóstico de enfermedad celiaca: 15 con peso normal y siete con sobrepeso/obesidad. Se tomaron biopsias de intestino delgado para la evaluación de la expresión de las interleuquinas a través de PCR a tiempo-real. Resultados: los niveles de expresión de las interleuquinas Th17 mostraron una tendencia a ser más altos en las biopsias de intestino de pacientes con sobrepeso/obesidad en comparación a los celiacos con peso normal, sin embargo, esta diferencia no fue significativa. Conclusión: el exceso de peso en pacientes celiacos no es influenciado por los niveles de expresión de interleuquinas Th17


Introduction: the histological alteration in the small intestine of the celiac patients produces a poor absorption that deteriorates or hinder an optimal weight gain. This can be the result of an increase expression of the Th17 gluten-specific interleukins. Objective: the aim of this study was to compare the expression of Th17 interleukins in celiac patients with normal and overweight/obese nutritional status. Methods: a total of 22 patients with newly diagnosed celiac disease were eligible: 15 patients with normal weight and seven overweight/obese. Small intestine biopsies were taken for the evaluation of the expression of interleukins through real-time PCR. Results: expression levels of Th17 interleukins showed a tendency to be higher in intestinal biopsies of overweight/obese patients compared to normal weight celiac subjects; however, this difference was not statistical significant. Conclusion: body weight excess in celiac patients is not influenced by the expression levels of Th17 interleukins


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Doença Celíaca/complicações , Doença Celíaca/genética , Interleucinas/genética , Interleucinas/metabolismo , Obesidade/genética , Sobrepeso/genética , Células Th17/metabolismo , Doença Celíaca/patologia , Intestino Delgado/patologia , Estado Nutricional , Obesidade/etiologia , Sobrepeso/etiologia
17.
Mol Biol Rep ; 45(5): 1245-1252, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30056589

RESUMO

Neutrophil elastase and myeloperoxidase enzymes have been implicated in high-fat diet-induced obesity, insulin resistance (IR) and atherosclerosis in animal models. The aim of the present study was to explore neutrophil elastase and myeloperoxidase mRNA expressions in the peripheral blood leukocytes (PBL) in overweight and obese subjects, and to correlate those mRNA expressions with BMI, IR and cardiovascular biomarkers. In this cross-sectional study, 74 apparently healthy subjects including 22 lean, 27 overweight and 25 obese subjects were recruited. Cardiovascular and metabolic biomarkers were evaluated from fasting blood samples. The mRNA levels of neutrophil elastase and myeloperoxidase genes in the PBL were quantified by real-time PCR. Compared to lean group, the overweight and obese groups showed significant upregulation of both neutrophil elastase (p < 0.001) and myeloperoxidase (p < 0.03) mRNA expressions in the PBL. But no difference was found between overweight and obese groups. The neutrophil elastase and myeloperoxidase mRNA levels showed significant positive correlation with BMI, serum triglyceride, atherogenic index of plasma and 10-year risk of developing cardiovascular disease. But no correlation was found with glucose, insulin or IR. It was concluded that the neutrophil elastase and myeloperoxidase genes are up-regulated in both overweight and obese subjects and are associated with BMI and markers of cardiovascular disease.


Assuntos
Elastase de Leucócito/genética , Obesidade/genética , Sobrepeso/genética , Peroxidase/genética , Regulação para Cima , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , Resistência à Insulina/genética , Masculino , Obesidade/sangue , Sobrepeso/sangue , Triglicerídeos/sangue
18.
Nutr Hosp ; 35(2): 305-311, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29756962

RESUMO

BACKGROUND: apolipoprotein E (ApoE) polymorphism is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease. OBJECTIVE: to evaluate the impact of ApoE2allele in lipid plasma levels and the influence of a healthy hypocaloric diet plus a controlled physical activity on the lipid profile, we performed a study in a cohort of overweight and obese healthy subjects (Body Mass Index (BMI) between 25 and 34.9 kg·m-2). METHODS: one hundred eighty participants (96 women), aged 18-50 years participated in a 22 weeks weight loss intervention based on same dietary treatment and different controlled exercise programs. All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure). Blood samples were obtained for lipids measurements at the beginning and end of the study. RESULTS: after intervention, men of the E2 group showed the greatest decreases in low-density lipoprotein (LDL), triglycerides (TG) and total cholesterol (TC) values (p = 0.039; p = 0.001; p = 0.001; respectively). For high-density lipoprotein (HDL), E2 group had significant differences compared with E4 at pre- (p = 0.020) and post-intervention values (p = 0.024). CONCLUSION: our results show great changes in men carrying ApoE2, mainly in TG and TC concentrations after treatment with hypocaloric diet and controlled exercise. Therefore, adding supervised training to nutritional intervention seems to be a good alternative for the reinforcement of the effect of the treatment.


Assuntos
Apolipoproteínas E/genética , Lipídeos/sangue , Perda de Peso/genética , Adulto , Apolipoproteína E2/genética , Estudos de Coortes , Dieta Redutora , Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/terapia , Sobrepeso/genética , Sobrepeso/terapia , Programas de Redução de Peso
19.
Genet Med ; 20(6): 583-590, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29758564

RESUMO

PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).MethodsSequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial. Associations between having a monogenic diabetes variant and clinical characteristics and time to treatment failure were analyzed.ResultsMore than 4% (22/488) had genetic variants causing monogenic diabetes (seven GCK, seven HNF4A, five HNF1A, two INS, and one KLF11). Patients with monogenic diabetes had a statistically, but not clinically, significant lower body mass index (BMI) z-score, lower fasting insulin, and higher fasting glucose. Most (6/7) patients with HNF4A variants rapidly failed TODAY treatment across study arms (hazard ratio = 5.03, P = 0.0002), while none with GCK variants failed treatment.ConclusionThe finding of 4.5% of patients with monogenic diabetes in an overweight/obese cohort of children and adolescents with T2D suggests that monogenic diabetes diagnosis should be considered in children and adolescents without diabetes-associated autoantibodies and maintained C-peptide, regardless of BMI, as it may direct appropriate clinical management.


Assuntos
Diabetes Mellitus Tipo 2/genética , Adolescente , Índice de Massa Corporal , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Masculino , Obesidade/complicações , Obesidade/genética , Sobrepeso/complicações , Sobrepeso/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
20.
Microrna ; 7(2): 148-154, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607782

RESUMO

BACKGROUND: Increased cardiovascular disease risk and prevalence associated with overweight and obesity is due, in part, to heightened inflammatory burden. The mechanisms underlying adiposity-related amplification of inflammation are not fully understood. Alterations in regulators of inflammatory processes such as microRNAs (miRs), however, are thought to play a pivotal role. OBJECTIVE: The aim of this study was to determine the influence of overweight and obesity, independent of other cardiovascular risk factors, on circulating expression of miR-34a, miR-126, miR-146a, miR-150 and miR-181b. METHODS: Forty-five sedentary, middle-aged (47-64 years) adults were studied: 15 were normal weight (8M/7F; BMI: 23.3 ± 0.3 kg/m2); 15 were overweight (8M/7F; 28.2 ± 0.3 kg/m2); and 15 were obese (7M/8F; 32.3 ± 0.5 kg/m2). All subjects were non-smokers, normotensive and free of overt cardiometabolic disease. Circulating levels of the following inflammation-related miRs: miR-34a, miR-126, miR-146a, miR-150 and miR-181b were determined in plasma using standard RT-PCR techniques. miR expression was normalized to exogenous C. elegans miR-39 and reported as relative expression (AU). RESULTS: Circulating miR-34a was ~200% higher (P< 0.05) in the obese as compared with normal weight and overweight groups. Whereas, miR-126, miR-146a and miR-150 were significantly lower (~65%) in both the obese and overweight groups than the normal weight group. There were no significant group differences in circulating expression of miR-181b. miR-34a was positively related (r = 0.43; P< 0.05); whereas, miR-126 (r = -0.48), miR-146a (r = -0.33) and miR-150 (r = -0.43) levels were significantly inversely related to BMI. CONCLUSION: Overweight and obesity, independent of other cardiometabolic risk factors, negatively influences circulating inflammation-related miRs. Dysregulation of circulating miRs may contribute mechanistically to the heightened inflammatory state associated with overweight and obesity.


Assuntos
MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Mediadores da Inflamação/sangue , Obesidade/sangue , Sobrepeso/sangue , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/imunologia , Sobrepeso/genética , Sobrepeso/imunologia , Prognóstico , Fatores de Risco
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