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1.
Adv Exp Med Biol ; 1193: 135-154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368102

RESUMO

Obesity is multifactorial and complex. Remarkable progress has been made recently in search for polygenic obesity through genome-wide association study (GWAS), but biology of polygenic effects on obesity is largely poor. This review summarizes the available evidence and provides an overview of the links between ALDH2 variants and adiposity, which were firstly and mainly derived from studies of polygenic obesity and also indirectly investigated by using cell lines and mice. The genetic association studies have observed consistent associations of ALDH2 variants with obesity-related traits including BMI, waist circumference (WC), waist-to-hip ratio (WHR), and visceral fat accumulation. In consideration of ALDH2 variants with enzyme activity and alcohol consumption behavior in physiological mechanism studies, we proposed a model by which the physiological and behavioral consequences of alcohol consumption serve as an intermediary process between polymorphisms in ALDH2 and obesity.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Obesidade/genética , Adiposidade/genética , Animais , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura , Relação Cintura-Quadril
2.
J Anim Sci ; 97(6): 2644-2657, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30959518

RESUMO

Sequencing technology, especially next-generation RNA sequencing, has greatly facilitated the identification and annotation of long noncoding RNAs (lncRNAs). In mammals, a large number of lncRNAs have been identified, which regulate various biological processes. An increasing number of lncRNAs have been identified which could function as key regulators of adipogenesis (adipocyte formation), a key step of the development of adipose tissue. Because proper adipose tissue development is a key factor affecting animal growth efficiency, lean/fat ratio, and meat quality, summarizing the roles and recent advances of lncRNAs in adipogenesis is needed in order to develop strategies to effectively manage fat deposition. In this review, we updated lncRNAs contributed to the regulation of adipogenesis, focusing on their roles in fat development of farm animals.


Assuntos
Adipogenia/genética , Tecido Adiposo/metabolismo , Adiposidade/genética , Animais Domésticos/genética , Carne/normas , RNA Longo não Codificante/genética , Adipócitos/fisiologia , Animais , Composição Corporal/genética , Crescimento e Desenvolvimento , Sequenciamento de Nucleotídeos em Larga Escala , Células-Tronco/fisiologia
3.
Gene ; 700: 47-51, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30902782

RESUMO

Intramuscular fat content (IMF) is one of the most significant factors for meat quality affecting tenderness, flavor, and juiciness of meat. For this reason, we aimed to investigate the association of SIRT1 gene polymorphisms with intramuscular fat content in Chinese Qinchuan cattle (Bos taurus). Using DNA sequencing, three single nucleotide polymorphisms (SNPs) within the promoter regions of SIRT1 gene were identified in 535 Qinchuan cattle, and the five haplotypes representing five potential different compositions of polymorphic potential cis-acting elements. Results indicated that both c.-107 G>A and c.-274 A>G were significantly associated with intramuscular fat content in Qinchuan cattle, and Hap5/5 diplotype showed higher (P < 0.05) intramuscular fat content than other combinations (P < 0.05 or P < 0.01). In addition, the Hap5 haplotype had much lower (P < 0.05) transcriptional activity, consistent with the association analysis. Based on our results, the polymorphisms in transcription factor binding sites of SIRT1 gene promoter may affect the transcriptional activity of SIRT1 gene, and thus alter intramuscular fat content in beef cattle.


Assuntos
Adiposidade/genética , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Sirtuína 1/genética , Células 3T3-L1 , Animais , Bovinos , Estudos de Associação Genética , Haplótipos , Camundongos , Músculo Esquelético/química , Regiões Promotoras Genéticas , Análise de Sequência de DNA
4.
Int J Mol Sci ; 20(5)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30823689

RESUMO

Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (n = 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including CPT1A intron 1 and SREBF1 intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of SREBF1 was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with CPT1A intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.


Assuntos
Adiposidade/genética , Carnitina O-Palmitoiltransferase/genética , Metilação de DNA , Ganho de Peso na Gestação/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Adulto , Índice de Massa Corporal , Carnitina O-Palmitoiltransferase/metabolismo , LDL-Colesterol/sangue , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
5.
Int J Mol Sci ; 20(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717287

RESUMO

Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.


Assuntos
Adiposidade/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo , Hiperlipidemias/metabolismo , Olanzapina/efeitos adversos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Administração Oral , Animais , Cloretos/metabolismo , Compostos de Cromo/metabolismo , Feminino , Regulação da Expressão Gênica , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/prevenção & controle , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/genética , Hiperinsulinismo/prevenção & controle , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/genética , Hiperlipidemias/prevenção & controle , Inflamação , Resistência à Insulina/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Ganho de Peso/efeitos dos fármacos
6.
PLoS Genet ; 15(2): e1007951, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30707692

RESUMO

Mendelian randomization (MR) has been used to estimate the causal effect of body mass index (BMI) on particular traits thought to be affected by BMI. However, BMI may also be a modifiable, causal risk factor for outcomes where there is no prior reason to suggest that a causal effect exists. We performed a MR phenome-wide association study (MR-pheWAS) to search for the causal effects of BMI in UK Biobank (n = 334 968), using the PHESANT open-source phenome scan tool. A subset of identified associations were followed up with a formal two-stage instrumental variable analysis in UK Biobank, to estimate the causal effect of BMI on these phenotypes. Of the 22 922 tests performed, our MR-pheWAS identified 587 associations below a stringent P value threshold corresponding to a 5% estimated false discovery rate. These included many previously identified causal effects, for instance, an adverse effect of higher BMI on risk of diabetes and hypertension. We also identified several novel effects, including protective effects of higher BMI on a set of psychosocial traits, identified initially in our preliminary MR-pheWAS in circa 115,000 UK Biobank participants and replicated in a different subset of circa 223,000 UK Biobank participants. Our comprehensive MR-pheWAS identified potential causal effects of BMI on a large and diverse set of phenotypes. This included both previously identified causal effects, and novel effects such as a protective effect of higher BMI on feelings of nervousness.


Assuntos
Índice de Massa Corporal , Adiposidade/genética , Adulto , Idoso , Ansiedade/genética , Bancos de Espécimes Biológicos , Estudos de Coortes , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Reino Unido
7.
J Physiol Biochem ; 75(1): 101-108, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30712161

RESUMO

With aging, there is a reduction in mitochondrial activity, and several changes occur in the body composition, including increased adiposity. The dysfunction of mitochondrial activity causes changes and adaptations in tissue catabolic characteristics. Among them, we can mention brown adipose tissue (BAT). BAT's main function is lipid oxidation for heat production, hence playing a role in adaptive thermogenesis induced by environmental factors such as exercise. It is known that exercise causes a series of metabolic changes, including loss body fat; however, there is still no consensus in the academic community about whether both strength and aerobic exercise equally reduces adiposity. Therefore, this study aimed to evaluate the effects of strength training and aerobic exercise regimes on adiposity, proteins regulating mitochondrial activity, and respiratory complexes in BAT of old rats. The rats were divided in two control groups: young control (YC; N = 5), and old control (OC; N = 5), and two exercise groups: strength training (OST; N = 5), and aerobic treadmill training (OAT; N = 5). Rats were subjected to an 8-week exercise regime, and their body composition parameters were evaluated (total body weight, adiposity index, and BAT weight). In addition, mitochondrial biogenesis proteins (PGC-1α, SIRT1, and pAMPK) and respiratory chain activity (complexes I, II/III, III, and IV) were evaluated. Results showed that OST and OAT exercise protocols significantly increased the mitochondrial regulatory molecules and respiratory chain activity, while body fat percentage and adiposity index significantly decreased. Taken together, both OST and OAT exercise increased BAT weight, activity of respiratory complexes, and regulatory proteins in BAT and equally reduced body adiposity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Adiposidade/genética , Envelhecimento/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Mitocôndrias/metabolismo , Condicionamento Físico Animal/fisiologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo , Envelhecimento/genética , Animais , Peso Corporal , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica , Mitocôndrias/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Termogênese/genética
8.
Clin Sci (Lond) ; 133(1): 23-40, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30606812

RESUMO

Obesity is a metabolic condition usually accompanied by insulin resistance (IR), type 2 diabetes (T2D), and dyslipidaemia, which is characterised by excessive fat accumulation and related to white adipose tissue (WAT) dysfunction. Enlargement of WAT is associated with a transcriptional alteration of coding and non-coding RNAs (ncRNAs). For many years, big efforts have focused on understanding protein-coding RNAs and their involvement in the regulation of adipocyte physiology and subsequent role in obesity. However, diverse findings have suggested that a dysfunctional adipocyte phenotype in obesity might be also dependent on specific alterations in the expression pattern of ncRNAs, such as miRNAs. The aim of this review is to update current knowledge on the physiological roles of miRNAs and other ncRNAs in adipose tissue function and their potential impact on obesity. Therefore, we examined their regulatory role on specific WAT features: adipogenesis, adipokine secretion, inflammation, glucose metabolism, lipolysis, lipogenesis, hypoxia and WAT browning. MiRNAs can be released to body fluids and can be transported (free or inside microvesicles) to other organs, where they might trigger metabolic effects in distant tissues, thus opening new possibilities to a potential use of miRNAs as biomarkers for diagnosis, prognosis, and personalisation of obesity treatment. Understanding the role of miRNAs also opens the possibility of using these molecules on individualised dietary strategies for precision weight management. MiRNAs should be envisaged as a future therapeutic approach given that miRNA levels could be modulated by synthetic molecules (f.i. miRNA mimics and inhibitors) and/or specific nutrients or bioactive compounds.


Assuntos
Adipócitos Brancos/metabolismo , Tecido Adiposo Branco/metabolismo , Adiposidade , MicroRNAs/metabolismo , Obesidade/metabolismo , Adipócitos Brancos/patologia , Adipogenia , Adipocinas/metabolismo , Tecido Adiposo Branco/patologia , Tecido Adiposo Branco/fisiopatologia , Adiposidade/genética , Animais , Metabolismo Energético , Regulação da Expressão Gênica , Marcadores Genéticos , Humanos , Mediadores da Inflamação/metabolismo , MicroRNAs/genética , MicroRNAs/uso terapêutico , Obesidade/genética , Obesidade/fisiopatologia , Obesidade/terapia , Fenótipo , Transdução de Sinais
9.
PLoS One ; 14(1): e0209581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30605457

RESUMO

OBJECTIVE: To study the association between mode of delivery and offspring BMI in late adolescence in a large cohort that predated the obesity epidemic, and assess the role of maternal pre-pregnancy BMI (ppBMI) in this association. STUDY DESIGN: We conducted a historical prospective study in the setting of the Jerusalem Perinatal Study (JPS), a population-based cohort that includes all 17,003 births to residents of West Jerusalem, between 1974 and 1976. Offspring's BMI at age 17 was obtained upon army recruitment and was available for 11,001 of cohort participants. The associations were examined using logistic regressions, adjusting for socio-demographic characteristics and for proxies for indication for C-Section birth. Analyses were then stratified by quartiles of ppBMI. RESULTS: C-Section was associated with offspring overweight/obesity, with adjusted OR of 1.44 (95%CI:1.14-1.82). Significant interaction of ppBMI with mode of delivery was observed, such that the associations of C-Section with overweight/obesity were limited to the upper quartile of ppBMI (adjusted OR = 1.70, 95%CI:1.18-2.43). Restricting the analyses to singleton first births and excluding pregnancies complicated with toxemia and gestational diabetes yielded similar findings. CONCLUSIONS: C-Section was positively associated with being overweight/obese at age 17. Importantly, ppBMI modified this association, with a significant association between C-Section and overweight/obesity evident only among offspring born to mothers in the highest ppBMI quartile. In light of the growing rates of obesity in women of reproductive age, these results should be considered in patient-doctor shared decisions related to selection of mode of delivery, in the absence of a clear medical indication.


Assuntos
Adiposidade/fisiologia , Tamanho Corporal/fisiologia , Obesidade/complicações , Adiposidade/genética , Adolescente , Adulto , Ordem de Nascimento , Peso ao Nascer , Índice de Massa Corporal , Cesárea , Estudos de Coortes , Parto Obstétrico/métodos , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Israel , Masculino , Mães , Obesidade/metabolismo , Razão de Chances , Sobrepeso/epidemiologia , Gravidez , Estudos Prospectivos
10.
BMC Genomics ; 20(1): 32, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630417

RESUMO

BACKGROUND: Positively correlated with carcass weight and animal growth, the ribeye area (REA) and the backfat thickness (BFT) are economic important carcass traits, which impact directly on producer's payment. The selection of these traits has not been satisfactory since they are expressed later in the animal's life and multigene regulated. So, next-generation technologies have been applied in this area to improve animal's selection and better understand the molecular mechanisms involved in the development of these traits. Correlation network analysis, performed by tools like WGCNA (Weighted Correlation Network Analysis), has been used to explore gene-gene interactions and gene-phenotype correlations. Thus, this study aimed to identify putative candidate genes and metabolic pathways that regulate REA and BFT by constructing a gene co-expression network using WGCNA and RNA sequencing data, to better understand genetic and molecular variations behind these complex traits in Nelore cattle. RESULTS: The gene co-expression network analysis, using WGCNA, were built using RNA-sequencing data normalized by transcript per million (TPM) from 43 Nelore steers. Forty-six gene clusters were constructed, between them, three were positively correlated (p-value< 0.1) to the BFT (Green Yellow, Ivory, and Light Yellow modules) and, one cluster was negatively correlated (p-value< 0.1) with REA (Salmon module). The enrichment analysis performed by DAVID and WebGestalt (FDR 5%) identified eight Gene Ontology (GO) terms and three KEGG pathways in the Green Yellow module, mostly associated with immune response and inflammatory mechanisms. The enrichment of the Salmon module demonstrated 19 GO terms and 21 KEGG pathways, related to muscle energy metabolism, lipid metabolism, muscle degradation, and oxidative stress diseases. The Ivory and Light yellow modules have not shown significant results in the enrichment analysis. CONCLUSION: With this study, we verified that inflammation and immune response pathways modulate the BFT trait. Energy and lipid metabolism pathways, highlighting fatty acid metabolism, were the central pathways associated with REA. Some genes, as RSAD2, EIF2AK2, ACAT1, and ACSL1 were considered as putative candidate related to these traits. Altogether these results allow us to a better comprehension of the molecular mechanisms that lead to muscle and fat deposition in bovine.


Assuntos
Adiposidade/genética , Bovinos/crescimento & desenvolvimento , Bovinos/genética , Desenvolvimento Muscular/genética , Animais , Bovinos/metabolismo , Metabolismo Energético/genética , Expressão Gênica , Redes Reguladoras de Genes , Estudos de Associação Genética , Metabolismo dos Lipídeos/genética , Redes e Vias Metabólicas/genética , Análise de Sequência de RNA
11.
Genet Epidemiol ; 43(3): 342-351, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30597647

RESUMO

Understanding the genetic and metabolic bases of obesity is helpful in planning and developing health strategies. Therefore, the first family-based joint linkage and linkage disequilibrium study was conducted in Iranian pedigrees to assess the relationship between obesity and single-nucleotide polymorphisms (SNPs) located in the 16q12.2 region. In the present study, a total of 13,344 individuals were included, of whom 12,502 individuals were within 3,109 pedigrees and 842 were unrelated singletons. To investigate the relationship between obesity and genetic variants, a joint model of linkage and linkage disequilibrium was applied. Moreover, a sequence kernel association test (SKAT) was used to evaluate the association of the SNP set with body size and lipid profile measurements. The joint model showed that rs13334070, in the intron 4 of the RPGRIP1L gene, has a significant association with obesity. According to the 4-gamete rule, which is a procedure for constructing SNP sets by considering recombination occurrence between SNPs, this polymorphism has a high correlation with six nearby SNPs that make an SNP set. SKAT showed that this SNP set has a significant association with body size factors, but almost no association with most of the lipid profile measurements. In conclusion, from the result of this study, it might be reasonable to consider RPGRIP1L as an important gene whose variations could be associated with obesity risk factors.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adiposidade/genética , Estudos de Associação Genética , Desequilíbrio de Ligação/genética , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Adulto Jovem
12.
Arch Cardiovasc Dis ; 112(2): 124-134, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30600215

RESUMO

BACKGROUND: The P2Y13 purinergic receptor regulates hepatic high-density lipoprotein uptake and biliary sterol secretion; it acts downstream of the membrane ecto-F1-adenosine triphosphatase, which generates extracellular adenosine diphosphate that selectively activates P2Y13, resulting in high-density lipoprotein endocytosis. Previous studies have shown that the serum concentration of the F1-adenosine triphosphatase inhibitor inhibitory factor 1 is negatively associated with cardiovascular risk. AIM: To evaluate whether p2y13 genetic variants affect cardiovascular risk. METHODS: Direct sequencing of the p2y13 coding and flanking regions was performed in a subcohort of 168 men aged 45-74 years with stable coronary artery disease and 173 control subjects from the GENES study. The two most frequent mutations, rs3732757 and rs1466684, were genotyped in 767 patients with coronary artery disease and 789 control subjects, and their association with cardiovascular risk markers was analysed. RESULTS: Carriers of the rs3732757 261T and rs1466684 557G alleles represented 9% and 27.5% of the entire population, respectively. The allele frequencies were identical in patients with coronary artery disease and control subjects. The presence of 261T was associated with higher concentrations of plasma lipoprotein A-I and inhibitory factor 1, increased fat mass and a lower heart rate. Moreover, the proportion of patients with coronary artery disease with a pejorative systolic ankle-brachial index was lower in carriers of the 261T allele. In both populations, the 557G allele was associated with increased concentrations of lipoprotein(a), and an allele dose effect was observed. CONCLUSIONS: Two frequent p2y13 variants are associated with specific bioclinical markers of cardiovascular risk. Although neither one of these variants appears to be related to the development of atherosclerotic disease, they may modulate the risk of additional cardiovascular complications.


Assuntos
Adiposidade/genética , Doença da Artéria Coronariana/genética , Frequência Cardíaca/genética , Lipoproteína(a)/sangue , Polimorfismo de Nucleotídeo Único , Proteínas/análise , Receptores Purinérgicos P2/genética , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , França , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Fatores de Risco
13.
Diab Vasc Dis Res ; 16(3): 244-253, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30537863

RESUMO

OBJECTIVE: The identification of circulating microRNAs related to abnormal metabolic function may be useful in the context of ageing, adiposity and insulin resistance. The miR-33 a/b has been shown to control the expression of genes involved in fatty acid biosynthesis, impaired metabolism and insulin resistance. In this study, we aimed to identify differences in circulating miR-33 a/b levels according to age-related metabolic impairment and increased adiposity. METHODS: This study included 80 individuals (30.2% with obesity, 70% females) classified according to insulin resistance (Stern's criteria) and age [young (20-39 years) and senior (40-59 years)]. Body fat was evaluated using bioelectrical impedance, biochemical markers by colorimetric, enzymatic and immuno-turbidimetry methods. TaqMan measures of circulating miR-33 a and miR-33 b with quantitative reverse transcription polymerase chain reaction in serum were assessed in association with clinical outputs. RESULTS: Circulating miR-33 a and miR-33 b levels showed significant association with fatness, the lipid profile and biomarkers of impaired glucose metabolism. Both miR-33 a and miR-33 b were associated with visceral adiposity index in non-insulin resistance and insulin resistance individuals. More important, for miR-33 a circulating levels in senior group, receiver operating characteristic curve analyses showed area under the curve 0.804 ( p = 0.010; 95% confidence interval = 0.655-0.952). CONCLUSION: Ageing influenced the relationship of circulating miR-33 a and miR-33 b with insulin resistance and increased adiposity.


Assuntos
Adiposidade , Envelhecimento/sangue , MicroRNA Circulante/sangue , Resistência à Insulina , MicroRNAs/sangue , Adiposidade/genética , Adulto , Envelhecimento/genética , Glicemia/metabolismo , MicroRNA Circulante/genética , Estudos Transversais , Impedância Elétrica , Feminino , Nível de Saúde , Humanos , Insulina/sangue , Resistência à Insulina/genética , Lipídeos/sangue , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
14.
Int. j. morphol ; 36(4): 1280-1284, Dec. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-975696

RESUMO

Determinar la distribución genotípica y la frecuencia alélica del polimorfismo rs17817449 del gen FTO en jóvenes chilenos y su influencia en variables antropométricas. Los 96 sujetos jóvenes (18-25 años), 43 hombres y 53 mujeres fueron evaluados utilizando genotipificación del polimorfismo rs17817449 del gen FTO en TT, TG y GG mediante polimerase chain reaction (PCR), además de una evaluación Kinenatropométrica para determinar las variables asociadas a composición corporal. Las variables fueron analizadas estadísticamente según su distribución paramétrica y el nivel de significancia estadística fue p<0,05. La distribución genotípica del polimorfismo rs17817449 de FTO en jóvenes chilenos fue: TT: 50 %; TG: 42,7 %; GG 7,3 % y la distribución alélica fue: T: 0,7105 y G: 0,2895. No se encontraron diferencias estadísticamente significativas en las variables antropométricas al analizar los participantes según modelo de dominancia del alelo G. Se determinó la distribución genotípica y la frecuencia alélica del polimorfismo rs17817449 del gen FTO en jóvenes chilenos, datos desconocidos hasta este momento. De acuerdo a nuestros resultados, no existen diferencias antropométricas entre personas con diferentes genotipos del polimorfismo rs17817449 de FTO, agrupadas según modelo de dominancia del alelo G.


The rs17817449 polymorphism of the FTO gene in young Chileans and their influence on anthropometric variables. 96 young subjects (18-25 years old), 43 men and 53 women were evaluated using genotyping of the rs17817449 polymorphism of the FTO gene in TT, TG and GG by means of polymerase chain reaction (PCR), in addition to a Kinenatropometric evaluation to determine the variables associated with body composition. The variables were analyzed statistically according to their parametric distribution and the level of statistical significance was p<0.05. The genotypic distribution of the FTO polymorphism rs17817449 in young Chileans was: TT: 50 %; TG: 42.7 %; GG 7.3 % and the allelic distribution was: T: 0.7105 and G: 0.2895. No statistically significant differences were found in the anthropometric variables when analyzing the participants according to model of dominance of the G allele. The genotypic distribution and the allelic frequency of the rs17817449 polymorphism of the gene were determined FTO in Chilean population, data unknown until now. According to our results, there are no anthropometric differences between people with different genotypes of the FTO polymorphism rs17817449, nor according to the dominance model of the G.


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Antropometria , Polimorfismo de Nucleotídeo Único , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Variação Genética , Índice de Massa Corporal , Chile , Reação em Cadeia da Polimerase , Adiposidade/genética , Circunferência da Cintura/genética , Frequência do Gene , Genótipo
15.
JAMA ; 320(24): 2553-2563, 2018 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-30575882

RESUMO

Importance: Body fat distribution, usually measured using waist-to-hip ratio (WHR), is an important contributor to cardiometabolic disease independent of body mass index (BMI). Whether mechanisms that increase WHR via lower gluteofemoral (hip) or via higher abdominal (waist) fat distribution affect cardiometabolic risk is unknown. Objective: To identify genetic variants associated with higher WHR specifically via lower gluteofemoral or higher abdominal fat distribution and estimate their association with cardiometabolic risk. Design, Setting, and Participants: Genome-wide association studies (GWAS) for WHR combined data from the UK Biobank cohort and summary statistics from previous GWAS (data collection: 2006-2018). Specific polygenic scores for higher WHR via lower gluteofemoral or via higher abdominal fat distribution were derived using WHR-associated genetic variants showing specific association with hip or waist circumference. Associations of polygenic scores with outcomes were estimated in 3 population-based cohorts, a case-cohort study, and summary statistics from 6 GWAS (data collection: 1991-2018). Exposures: More than 2.4 million common genetic variants (GWAS); polygenic scores for higher WHR (follow-up analyses). Main Outcomes and Measures: BMI-adjusted WHR and unadjusted WHR (GWAS); compartmental fat mass measured by dual-energy x-ray absorptiometry, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, type 2 diabetes, and coronary disease risk (follow-up analyses). Results: Among 452 302 UK Biobank participants of European ancestry, the mean (SD) age was 57 (8) years and the mean (SD) WHR was 0.87 (0.09). In genome-wide analyses, 202 independent genetic variants were associated with higher BMI-adjusted WHR (n = 660 648) and unadjusted WHR (n = 663 598). In dual-energy x-ray absorptiometry analyses (n = 18 330), the hip- and waist-specific polygenic scores for higher WHR were specifically associated with lower gluteofemoral and higher abdominal fat, respectively. In follow-up analyses (n = 636 607), both polygenic scores were associated with higher blood pressure and triglyceride levels and higher risk of diabetes (waist-specific score: odds ratio [OR], 1.57 [95% CI, 1.34-1.83], absolute risk increase per 1000 participant-years [ARI], 4.4 [95% CI, 2.7-6.5], P < .001; hip-specific score: OR, 2.54 [95% CI, 2.17-2.96], ARI, 12.0 [95% CI, 9.1-15.3], P < .001) and coronary disease (waist-specific score: OR, 1.60 [95% CI, 1.39-1.84], ARI, 2.3 [95% CI, 1.5-3.3], P < .001; hip-specific score: OR, 1.76 [95% CI, 1.53-2.02], ARI, 3.0 [95% CI, 2.1-4.0], P < .001), per 1-SD increase in BMI-adjusted WHR. Conclusions and Relevance: Distinct genetic mechanisms may be linked to gluteofemoral and abdominal fat distribution that are the basis for the calculation of the WHR. These findings may improve risk assessment and treatment of diabetes and coronary disease.


Assuntos
Gordura Abdominal , Adiposidade/genética , Doença das Coronárias/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Variação Genética , Relação Cintura-Quadril , Índice de Massa Corporal , Doenças Cardiovasculares/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
J Int Soc Sports Nutr ; 15(1): 40, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30124167

RESUMO

BACKGROUND: A single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is a strong predictor of obesity in humans. The FTO SNP (rs1421085) results in a T to C nucleotide substitution that may result in an increased risk for obesity in individuals who carry at least one C allele. The purpose of this investigation was to characterize the FTO genotype in a cohort of exercise-trained men and women. METHODS: We tested 108 exercise-trained individuals that included professional mixed martial arts fighters, competitive distance runners, collegiate swimmers, stand-up paddlers as well as a cohort of recreational bodybuilders. Body composition was assessed via dual-energy x-ray absorptiometry (DXA). Saliva samples were collected in order to genotype participants and quantify cortisol levels. RESULTS: The physical characteristics of the subjects were as follows (mean±SD): body weight 74.5±15.6 kg; height 171.5±9.5 cm; bone mineral content 2.8±0.7 kg; fat mass 15.7±5.5 kg; lean body mass 55.9±14.4 kg; % body fat 21.6±7.0. Independent samples t tests showed that C allele carriers (n = 54) had significantly higher fat mass t(106) = 3.13, p < 0.01 and body fat percentage t(106) = 2.68, p < 0.01, relative to the TT group (n = 54) (i.e., fat mass: C/- 17.3 ±5.6 kg, TT 14.2±4.6 kg; body fat percentage: C/- group 23.4±7.4%, TT group 19.9±6.2). No other measures of body composition were associated with the FTO genotype (i.e., body mineral density, bone mineral content, or lean body mass). Moreover, cortisol levels were significantly higher in the TT group relative to the C allele carriers t(106) = 2.37, p = 0.02 (i.e., TT 0.35 ±0.35 µg/dL, C/- 0.22±0.16 µg/dL). CONCLUSIONS: Our findings demonstrate a relationship between C allele carriers on the FTO gene and a predisposition to a higher fat mass and body fat percentage. In addition, we found no relationship between cortisol and fat mass. However, due to the cross-sectional nature of this investigation, we cannot infer causality regarding the FTO gene and body composition.


Assuntos
Adiposidade/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Exercício , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Absorciometria de Fóton , Composição Corporal , Estudos Transversais , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino
17.
Rev Med Chil ; 146(6): 717-726, 2018 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-30148903

RESUMO

BACKGROUND: Numerous studies have identified the role of Fat-mass-associated-gene (FTO) in the development of obesity. AIM: To investigate the association of FTO gene with adiposity markers in Chilean adults. MATERIAL AND METHODS: 409 participants were included in this cross-sectional study. The association between FTO (rs9939609) genotype and adiposity markers was determined using linear regression analyses. Adiposity markers included were: body weight, body mass index, fat mass, waist circumference, hip circumference and waist/hip ratio. RESULTS: A fully adjusted model showed a significant association between FTO genotype and body weight (2.16 kg per each extra copy of the risk allele [95% confidence intervals (CI): 0.45 to 3.87], p = 0.014), body mass index (0.61 kg.m-2 [95% CI: 0.12 to 1.20], p = 0.050) and fat mass (1.14% [95% CI: 0.39 to 1.89], p = 0.010). The greater magnitude of association was found between the FTO gene and fat mass when the outcomes were standardized to z-score. CONCLUSIONS: This study confirms an association between the FTO gene and adiposity markers in Chilean adults, which is independent of major confounding factors.


Assuntos
Adiposidade/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Genótipo , Obesidade/genética , Adiposidade/etnologia , Adulto , Alelos , Antropometria , Chile/etnologia , Estudos Transversais , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Estilo de Vida , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Valores de Referência , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
18.
Toxicol Lett ; 295: 99-114, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29908848

RESUMO

Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-ß and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Obesidade/induzido quimicamente , Ovário/efeitos dos fármacos , Compostos de Trialquitina/toxicidade , Adipogenia/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Adiposidade/genética , Animais , Atrofia , Colesterol/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Ciclo Estral/sangue , Ciclo Estral/efeitos dos fármacos , Feminino , Fibrose , Regulação Enzimológica da Expressão Gênica , Hormônios Esteroides Gonadais/sangue , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Ovário/metabolismo , Ovário/patologia , Ovário/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Doença Inflamatória Pélvica/induzido quimicamente , Doença Inflamatória Pélvica/metabolismo , Doença Inflamatória Pélvica/patologia , Doença Inflamatória Pélvica/fisiopatologia , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar
19.
Genome Biol ; 19(1): 74, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880058

RESUMO

We discuss a recent study that has identified and validated the link between a type-2 diabetes (T2D) association and human adipose biology by means of KLF14 gene expression. In addition to being maternally imprinted, the contributed risk at this locus is greater in female carriers.


Assuntos
Adiposidade/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Animais , Diabetes Mellitus Tipo 2/genética , Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , Fatores de Transcrição Sp/genética
20.
J Biosci ; 43(2): 329-337, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29872021

RESUMO

Maternal high-fat diet (HFD) consumption during pregnancy and lactation affects metabolic outcomes and lipid metabolism of offspring in later life in a gender-specific manner. However, it is not known whether maternal HFD alters bile acid metabolism in adult mice offspring. The purpose of this study was to elucidate the relationship between maternal HFDinduced metabolic diseases and bile acid metabolism in male and female adult mice offspring. Female mice were fed either standard chow (C) or HFD (H) for 10 weeks pre-pregnancy until lactation. After weaning, offspring were fed a chow diet until 11 weeks of age, then challenged with either C or H diet for 4 weeks, and divided into eight groups in accordance with mother's and offspring's diets: male(M) CC, MHC, MCH, MHH, female(F) CC, FHC, FCH, and FHH. MHH showed greater weight gain compared to FHH. Liver weight was higher in MHH than in FHH. Serum total cholesterol levels were higher in MHH than in MHC, and tended to be higher in MHH than in FHH. Serum glucose levels were higher in MHH than in MHC. Hepatic triglyceride levels were higher in MHH than in MHC. Hepatic mRNA expression of bile acid uptake transporters Oatp1a1 and Oatp1b2 was increased in MHH, compared to MCH. Hepatic mRNA expression of HMGCoAR, Cyp7a1, Sult2a1, and Oatp1a4 was increased in FHH, compared to FCH. In conclusion, maternal HFD consumption may promote bile acid synthesis, sulfation and excretion in female offspring fed a HFD, which may confer resistance to HFDinduced metabolic phenotypes.


Assuntos
Ácidos e Sais Biliares/metabolismo , Lactação/genética , Metabolismo dos Lipídeos/genética , Obesidade/genética , Adiposidade/genética , Animais , Ácidos e Sais Biliares/genética , Peso Corporal/genética , Dieta Hiperlipídica , Feminino , Regulação da Expressão Gênica , Humanos , Lactação/metabolismo , Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Obesidade/metabolismo , Obesidade/patologia , Gravidez , Caracteres Sexuais , Desmame
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