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1.
Ann Agric Environ Med ; 27(3): 407-412, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955223

RESUMO

INTRODUCTION AND OBJECTIVE: The biochemical and anthropometric consequences of metabolic disorders exert an enormous effect on the functioning of people worldwide. The aim of this study is to assess relationships between biochemical and anthropometric parameters associated with metabolic syndrome, and the presence of the PPAR-γ rs1801282, the FTO rs9939609, and the MC4R rs17782313 polymorphisms in women aged 45-60. MATERIAL AND METHODS: The study included 425 women, aged 45-59 years, from the general population of the West Pomeranian Province in north-west Poland. The research procedure involved a structured interview, anthropometric and blood pressure measurements, biochemical analysis of serum, and genetic analysis. RESULTS: The carriers of the A/A genotype of the FTO polymorphism had higher LDL levels than their counterparts with the T/T genotype (p = 0.01). The carriers of the T/T genotype of the MC4R polymorphism had lower non-HDL levels than those with the C/C and C/T genotypes (p = 0.019). Weight was related to the C/C and the C/G + G/G genotypes of the PPAR-γ gene polymorphism (p = 0.046). The model of inheritance for the MC4R polymorphism had a significant effect on TG (p = 0.039) and non-HDL (p = 0.05) levels. CONCLUSIONS: The genotypes analyzed in the study had only a slight direct effect on the biochemical and anthropometric abnormalities typical of metabolic disorders. Nonetheless, the risk alleles (A allele of the FTO rs9939609 and the C allele of the MC4R rs17782313) were found to be related to lipid metabolism disorders in 45-60-year-old women.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Antropometria , Predisposição Genética para Doença , Síndrome Metabólica/genética , PPAR gama/genética , Receptor Tipo 4 de Melanocortina/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , PPAR gama/metabolismo , Polônia , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/metabolismo
2.
High Blood Press Cardiovasc Prev ; 27(5): 363-371, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32740853

RESUMO

Epigenetic processing takes centre stage in cardiometabolic diseases (obesity, metabolic syndrome, type 2 diabetes, hypertension), where it participates in adiposity, inflammation, endothelial dysfunction, vascular insulin resistance and atherosclerosis. Epigenetic modifications, defined as heritable changes in gene expression that do not entail mutation in the DNA sequence, are mainly induced by environmental stimuli (stress, pollution, cigarette smoking) and are gaining considerable interest due to their causal role in cardiovascular disease, and their amenability to pharmacological intervention. Importantly, epigenetic modifications acquired during life can be transmitted to the offspring and exert their biological effects across multiple generations. Indeed, such transgenerational transmission of epigenetic signals may contribute to anticipating cardiovascular and metabolic disease phenotypes already in children and young adults. A deeper understanding of environmental factors and their effects on the epigenetic machinery and transcriptional programs is warranted to develop effective mechanism-based therapeutic strategies. The clinical application of epigenetic drugs-also known as "epi-drugs"-is currently exploding in the field of cardiovascular disease. The present review describes the main epigenetic networks underlying cardiometabolic alterations and sheds light on specific points of intervention for pharmacological reprogramming in this setting.


Assuntos
Doenças Cardiovasculares/genética , Endotélio Vascular/metabolismo , Epigênese Genética , Síndrome Metabólica/genética , Animais , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Epigênese Genética/efeitos dos fármacos , Interação Gene-Ambiente , Humanos , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Fatores de Risco , Transdução de Sinais
3.
Vasc Health Risk Manag ; 16: 249-256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612360

RESUMO

Background: The role of metabolic states in cardiovascular risks among individuals with varying degrees of obesity is unknown. The study aimed to compare cardiometabolic index (CMI), atherogenic index of plasma (AIP), lipid accumulation product (LAP) and novel anthropometric indices in metabolic and non-metabolically obese individual with regard to the role of FTO gene in Iranian adults. Methods: In total, 165 individuals were recruited into this cross-sectional study. Individuals grouped into four groups: metabolic healthy normal-weight (MHNW) individuals, metabolically unhealthy normal-weight (MUNW) individuals, metabolically healthy obese (MHO) individuals and metabolic unhealthy obese (MUO) individuals. The dietary intake was evaluated by food frequency questionnaire (FFQ). The cardiovascular indices (CMI, AIP and LAP) were calculated. A variety of anthropometric indices were calculated, including body adiposity Index (BAI), weight-adjusted-waist index (WWI), A body shape index (ABSI) and waist-height ratio (WHR). The genotypes of FTO-rs9939609 subjects were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The individuals with metabolically unhealthy phenotypes (MUO, MUNW) have higher levels of triglyceride and cardiovascular indices (AIP, LAP and CMI) than the individuals with metabolic healthy phenotypes (MHO, MHNW). With a similar degree of obesity, the anthropometric indices (BAI, WWI and WHR) levels were higher in metabolic unhealthy groups than metabolically healthy groups. The highest frequency of obesity-risk allele AA of FTO gene was observed in MUO, MHO, MUNW and MHNW, respectively. Conclusion: Normal-weight individuals with metabolic unhealthy status are at higher risk for cardiovascular diseases than obese individuals with metabolically healthy status. The genotype frequencies of obesity-risk allele AA of FTO gene were higher in obesity phenotypes than metabolic phenotypes.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Doenças Cardiovasculares/genética , Metabolismo Energético/genética , Síndrome Metabólica/genética , Obesidade Metabolicamente Benigna/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Antropometria , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade Metabolicamente Benigna/sangue , Obesidade Metabolicamente Benigna/diagnóstico , Fenótipo , Medição de Risco , Fatores de Risco , Adulto Jovem
4.
Am J Clin Nutr ; 112(2): 373-380, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32511694

RESUMO

BACKGROUND: Evidence suggests low-grade inflammation as the cause of metabolic syndrome and suggests diet as a promoter of chronic inflammation. OBJECTIVE: We evaluated the association between inflammatory diets and the development of metabolic syndrome in Mexican adults. METHODS: A total of 399 participants of the Health Workers Cohort Study were included in this study. The follow-up period was 13 y. Metabolic syndrome definition was the presence of ≥3 of the following components: waist circumference ≥102 cm for males or ≥88 cm for females, blood pressure ≥130 mmHg for systolic or ≥85 mmHg for diastolic, HDL cholesterol <40 mg/dL for males and <50 mg/dL for females; triglycerides ≥150 mg/dL, and glucose ≥100 mg/dL. To evaluate the inflammatory potential of the diet we used the Dietary Inflammatory Index (DII), which was divided into quartiles. To assess the risk of metabolic syndrome we estimated HRs and 95% CIs using Cox proportional hazards models. RESULTS: After adjustment for potential confounders, we found a positive association between participants in the highest quartile (Q) of DII and the incidence of metabolic syndrome (HRQ4vsQ1 = 1.99; 95% CI: 1.03, 3.85; P-trend = 0.04) over a period of 13 y. When we divided the metabolic syndrome by its components, we found that participants in the highest quartile of DII were associated with hypertriglyceridemia (HRQ4vsQ1 = 2.28; 95% CI: 1.13, 4.57; P-trend = 0.01), hypertension (HRQ4vsQ1 = 2.22; 95% CI: 1.03, 4.77; P-trend = 0.032), and abdominal obesity (HRQ4vsQ1 = 2.68; 95% CI: 1.06, 6.79; P-trend = 0.02). CONCLUSIONS: A highly inflammatory diet is associated with metabolic syndrome, hypertension, abdominal obesity, and hypertriglyceridemia. Further studies are needed to corroborate the role of inflammation and diet in the development of metabolic syndrome; yet, a reduction in dietary components that have been linked to inflammation is desirable.


Assuntos
Dieta/efeitos adversos , Síndrome Metabólica/etnologia , Síndrome Metabólica/imunologia , Adulto , Glicemia/metabolismo , Pressão Sanguínea , HDL-Colesterol/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/fisiopatologia , Americanos Mexicanos , Pessoa de Meia-Idade , Triglicerídeos/metabolismo
5.
Chemosphere ; 255: 127000, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417515

RESUMO

BACKGROUND: Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood. OBJECTIVE: To determine the impact of prenatal BPA exposure on genome-wide gene expression of VAT and SAT depots. METHODS: RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Gene expression and pathway differences between SAT and VAT depots with or without prenatal BPA-treatment and the effect of prenatal BPA treatment on each depot were tested. RESULTS: There were 179 differentially expressed genes (padjusted < 0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. These adipose depot-specific genes and pathways were consistent with prenatal BPA-treatment. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways. CONCLUSION: Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin pathways, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.


Assuntos
Adiposidade/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Gordura Subcutânea/efeitos dos fármacos , Adiposidade/genética , Animais , Compostos Benzidrílicos/sangue , Regulação para Baixo , Disruptores Endócrinos/sangue , Feminino , Perfilação da Expressão Gênica , Inflamação , Gordura Intra-Abdominal/crescimento & desenvolvimento , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Fenóis/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , RNA/genética , RNA/metabolismo , Ovinos , Gordura Subcutânea/crescimento & desenvolvimento , Gordura Subcutânea/metabolismo
6.
PLoS One ; 15(5): e0227720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407314

RESUMO

Numerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erbα) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erbα expression induces muscular atrophy, high adiposity, and metabolic syndrome in mice. Here we show that, unlike knockout mice, Nr1d1 heterozygous mice are not susceptible to muscular atrophy and in fact paradoxically possess larger myofiber diameters and improved neuromuscular function, compared to wildtype mice. Heterozygous mice lacked dyslipidemia, a characteristic of Nr1d1 knockout mice and displayed increased whole-body fatty-acid oxidation during periods of inactivity (light cycle). Heterozygous mice also exhibited higher rates of glucose uptake when fasted, and had elevated basal rates of gluconeogenesis compared to wildtype and knockout littermates. Rev-erbα ablation suppressed glycolysis and fatty acid-oxidation in white-adipose tissue (WAT), whereas partial Rev-erbα loss, curiously stimulated these processes. Our investigations revealed that Rev-erbα dose-dependently regulates glucose metabolism and fatty acid oxidation in WAT and muscle.


Assuntos
Dislipidemias/genética , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Animais , Comportamento Animal/fisiologia , Relógios Circadianos/genética , Dislipidemias/metabolismo , Dislipidemias/patologia , Ácidos Graxos/metabolismo , Gluconeogênese/genética , Glucose/metabolismo , Heterozigoto , Humanos , Metabolismo dos Lipídeos/genética , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Camundongos Knockout , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Miofibrilas/genética , Miofibrilas/metabolismo , Miofibrilas/patologia , Fotoperíodo
8.
Proc Natl Acad Sci U S A ; 117(18): 9840-9850, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32303655

RESUMO

Deregulation of mitochondrial dynamics leads to the accumulation of oxidative stress and unhealthy mitochondria; consequently, this accumulation contributes to premature aging and alterations in mitochondria linked to metabolic complications. We postulate that restrained mitochondrial ATP synthesis might alleviate age-associated disorders and extend healthspan in mammals. Herein, we prepared a previously discovered mitochondrial complex IV moderate inhibitor in drinking water and orally administered to standard-diet-fed, wild-type C57BL/6J mice every day for up to 16 mo. No manifestation of any apparent toxicity or deleterious effect on studied mouse models was observed. The impacts of an added inhibitor on a variety of mitochondrial functions were analyzed, such as respiratory activity, mitochondrial bioenergetics, and biogenesis, and a few age-associated comorbidities, including reactive oxygen species (ROS) production, glucose abnormalities, and obesity in mice. It was found that mitochondrial quality, dynamics, and oxidative metabolism were greatly improved, resulting in lean mice with a specific reduction in visceral fat plus superb energy and glucose homeostasis during their aging period compared to the control group. These results strongly suggest that a mild interference in ATP synthesis through moderation of mitochondrial activity could effectively up-regulate mitogenesis, reduce ROS production, and preserve mitochondrial integrity, thereby impeding the onset of metabolic syndrome. We conclude that this inhibitory intervention in mitochondrial respiration rectified the age-related physiological breakdown in mice by protecting mitochondrial function and markedly mitigated certain undesired primary outcomes of metabolic syndrome, such as obesity and type 2 diabetes. This intervention warrants further research on the treatment of metabolic syndrome of aging in humans.


Assuntos
Envelhecimento/genética , Síndrome Metabólica/metabolismo , Mitocôndrias/genética , Estresse Oxidativo/genética , Trifosfato de Adenosina/biossíntese , Trifosfato de Adenosina/genética , Envelhecimento/metabolismo , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/genética , Glucose/metabolismo , Envelhecimento Saudável/genética , Humanos , Gordura Intra-Abdominal/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Biogênese de Organelas , Espécies Reativas de Oxigênio/metabolismo
9.
PLoS One ; 15(4): e0230769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32259832

RESUMO

Bottlenose dolphins (Tursiops truncatus) are long-lived mammals that can develop chronic aging-associated conditions similar to humans, including metabolic syndrome. Initial studies suggest that these conditions may be attenuated in dolphins using a modified fish diet. Serum metabolomics, fatty acid panels, and blood-based health indices were compared between 20 dolphins on a modified, 50% wild-type diet (50% mullet, 25% capelin, and 25% squid and/or herring) and 10 dolphins on a baseline diet (75% capelin and 25% squid and/or herring). Blood samples were collected at Months 0, 1, 3 and 6. Dolphins on the modified diet had lower insulin (7.5 ± 4.0 and 14.8 ± 14.0 µIU/ml, P = 0.039), lower cholesterol (160 ± 26 and 186 ± 24 mg/dl, P = 0.015) and higher hematocrit (46 ± 3 and 44 ± 3%, P = 0.043) by Month 1 compared to controls. Dolphins with anemia (hemoglobin ≤ 12.5 g/dl, n = 6) or low-normal hemoglobin (12.5-13.5 g/dl, n = 3) before placed on the modified diet had normal hemoglobin concentrations (> 13.5 g/dl) by Month 3. The modified diet caused a significant shift in the metabolome, which included 664 known metabolites. Thirty prioritized metabolites at Months 1 and 3 were 100% predictive of dolphins on the modified diet. Among 25 prioritized lipids, 10 (40%) contained odd-chain saturated fatty acids (OCFAs); C15:0 was the highest-prioritized OCFA. Increased dietary intake of C15:0 (from 1.3 ± 0.4 to 4.5 ± 1.1 g/day) resulted in increased erythrocyte C15:0 concentrations (from 1.5 ± 0.3 to 5.8 ± 0.8 µg/ml, P < 0.0001), which independently predicted raised hemoglobin. Further, increasing age was associated with declining serum C15:0 (R2 = 0.14, P = 0.04). While higher circulating OCFAs have been previously associated with lower risks of cardiometabolic diseases in humans, further studies are warranted to assess potential active roles of OCFAs, including C15:0, in attenuating anemia.


Assuntos
Anemia/etiologia , Anemia/metabolismo , Golfinho Nariz-de-Garrafa/sangue , Golfinho Nariz-de-Garrafa/metabolismo , Ácidos Graxos/metabolismo , Peixes/sangue , Peixes/metabolismo , Metaboloma/fisiologia , Animais , Colesterol/metabolismo , Dieta/métodos , Feminino , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo
10.
Per Med ; 17(2): 111-119, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125933

RESUMO

Aim: Metabolic syndrome (MetS) diagnosed in the dialysis patients is increasingly reported which worsens the prognosis of the renal diseases. The relationship of SCD1 with MetS is largely unknown. The purpose of this study was to investigate the relationship between SCD1 polymorphism and MetS in dialysis patients. Methods: A cross-sectional study was conducted on 323 Chinese dialysis patients, and the correlation between the seven SNPs of SCD1 gene (rs10883465, rs2060792, rs1502593, rs522951, rs3071, rs3978768 and rs1393492) and MetS was analyzed. Results: One tag-SNP (rs1393492) has significantly associated with the prevalence of MetS. Dialysis patients with rs1393492 AA genotype of SCD1 are more prone to MetS (p = 0.021). Conclusion: This study shows that the rs1393492 variations of SCD1 gene are related with the development of MetS in Chinese dialysis patients.


Assuntos
Nefropatias/terapia , Síndrome Metabólica/epidemiologia , Polimorfismo de Nucleotídeo Único , Estearoil-CoA Dessaturase/genética , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Prevalência , Diálise Renal
11.
Medicine (Baltimore) ; 99(6): e18820, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028392

RESUMO

Cross-sectional studies indicate that the fat mass and obesity-associated (FTO) rs9939609 gene variant is associated with metabolic syndrome (MetS) primarily in European ancestry. However, the association is not fully elucidated in African Americans.We hypothesized that rs9939609 (AT = moderate-risk carriers or AA = high-risk carriers compared to TT = low-risk carriers) is associated with MetS and its component risk factors over time; and that its association is ancestry-specific. A secondary hypothesis was that higher levels of physical activity can decrease the deleterious effect of rs9939609 at higher body mass index (BMI).Atherosclerosis Risk in Communities study repeated measures data from 4 visits (1987-1998) were obtained from the database of Genotypes and Phenotypes for 10,358 participants (8170 Whites and 2188 African Americans) aged 45 to 64 years at baseline. Guidelines for elevated blood pressure by the American College of Cardiology and American Heart Association Task Force were updated within the MetS criteria. Risk ratios (RR) and 95% confidence intervals from generalized estimating equations assessed population-average risks.MetS was present among 3479 (42.6%) Whites and 1098 (50.2%) African Americans at baseline, and 50.3% Whites and 57% African Americans over 11-years of follow-up. Among MetS component risk factors, high waist circumference was most prevalent among White AT (RR = 1.07; 1.06-1.09) and AA (RR = 1.12; 1.10-1.14) higher-risk carriers. High triglycerides were elevated among African American AA high-risk carriers (RR = 1.11; 1.02-1.21) compared to TT low-risk carriers. Over time, White AT-and AA higher-risk carriers had 1.07 and 1.08-fold increase (P < .0001) in MetS risk. Physical activity had independent protective effects on MetS among both races (P < .05). White AA high-risk carriers with normal BMI and low vs high physical activity had higher MetS risk (RR = 1.69; 1.25-2.30 and RR = 0.68;0.53-0.87, respectively). In rs9939609 × BMI× physical activity interaction, White A-allele high-risk carriers had lower MetS risk (RR = 0.68; 0.53-0.87). Among Whites, physical activity can lessen the effect of rs9939609 and high BMI on risk for MetS.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Predisposição Genética para Doença , Síndrome Metabólica/genética , Afro-Americanos , Idoso , Índice de Massa Corporal , Bases de Dados Factuais , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade , Fatores de Risco , Estados Unidos
12.
Gene ; 738: 144476, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061761

RESUMO

BACKGROUND: Metabolic syndrome (MetS) contributes to increased risk of morbidity and mortality. The United Arab Emirates (UAE) has a high prevalence of MetS which may be linked to modifiable and genetic risk factors in the local population. The association between MetS as a phenotype and key genetic variants in the UAE has not been investigated. This study reports on the clinical, biochemical and genetic associations of MetS and its risk factors to improve individualized medicine outcomes. METHODS: There were 471 subjects included in this cross-sectional study, 367 with MetS and 104 without MetS. Along with clinical and laboratory parameters, multiple risk genetic variants were tested for their association with MetS, which include 49 variants that have previously been shown to be linked with MetS development as a phenotype, 116 variants for association with waist-hip ratio (WHR), 398 variants with body-mass index (BMI), 213 variants with T2DM and insulin resistance, 307 variants with different lipid traits, 308 variants with blood pressure traits, and 64 variants with coronary and cerebrovascular accidents. RESULTS: Patients with MetS had higher rates of type 2 diabetes mellitus (T2DM), hypertension and dyslipidemia (p < 0.0001). Waist circumference and T2DM were identified as the key risk factors for MetS development. Individuals with MetS were also found to have a higher rate of clinical complications than those without MetS (76% vs. 52%). Several gene variants including those of the FTO gene were found to be associated with a predisposition to developing MetS or some of its components (PFTO ~0.005-0.009). CONCLUSIONS: This study showed associations between MetS as well as clinical factors contributing to MetS and specific genetic and metabolic risk factors, providing an insight into the metabolic and genetic links to disease development. Knowledge with respect to population specific risk markers including at risk genotypes will help in early identification of individuals with increased susceptibility to MetS in the UAE and provide the opportunity for timely intervention to prevent or delay the onset of MetS.


Assuntos
Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Prevalência , Fatores de Risco , Emirados Árabes Unidos/epidemiologia , Circunferência da Cintura , Relação Cintura-Quadril
13.
BMC Cardiovasc Disord ; 20(1): 57, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019489

RESUMO

BACKGROUND: Although the Melanocortin-4 Receptor (MC4R) gene rs17782313 C/T has been consistently related to obesity risk, the interaction between MC4R polymorphism and diet quality indices on cardio-metabolic risk factors has not yet investigated. Therefore we aimed to test this hypothesis. METHODS: This cross-sectional study recruited 188 (96 males and 92 females) healthy obese adults aged 20-50 years. Diet quality indices including Healthy Eating Index-2015 (HEI-2015) and Diet Quality Index-International (DQI-I) were constructed using data from a validated food frequency questionnaire. MC4R s17782313 were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The interaction between MC4R polymorphism and diet quality indices was tested by Analysis of covariance (ANCOVA) multivariate interaction model. RESULTS: There were significant gene-diet interactions between rs17782313 and HEI-2015 (P Interaction < 0.05) in modulating low-density lipoprotein cholesterol (LDL-C) levels among female group; rare allele heterozygotes of rs17782313 had highest mean of LDL-C concentration when placed in second tertile of HEI (P < 0.05). Moreover, rs17782313 and both indices (HEI and DQI-I) had significant interaction on serum glucose concentrations, systolic and diastolic blood pressure (SBP, DBP) in males (P Interaction < 0.05); when adherence to these indices was low, the obesity risk allele was associated with serum glucose concentrations, SBP and DBP. These gene-diet interactions remained significant even after adjustment for potential confounders. CONCLUSION: Our study showed that MC4R rs17782313 interacts with adherence to the dietary quality indices (HEI and DQI-I) to influence several cardio-metabolic risk factors in obese male and females. Further large prospective studies are warranted to confirm our findings.


Assuntos
Proteína Relacionada com Agouti/sangue , Dieta Saudável , Síndrome Metabólica/genética , Valor Nutritivo , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética , alfa-MSH/sangue , Adulto , Regulação do Apetite , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , LDL-Colesterol/sangue , Estudos Transversais , Comportamento Alimentar , Feminino , Interação Gene-Ambiente , Humanos , Irã (Geográfico) , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Cooperação do Paciente , Medição de Risco , Fatores de Risco , Adulto Jovem
14.
Obesity (Silver Spring) ; 28(3): 493-501, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090516

RESUMO

OBJECTIVE: This study investigated whether the levels of specific serum microRNAs (miRNAs) were altered following diet-induced weight loss and whether the serum miRNAs differed in the presence of the metabolic syndrome. METHODS: The study was a weight loss intervention trial with a prescribed energy deficit of approximately 500 kcal/d. Levels of 22 miRNAs were determined in serum samples from 85 participants with overweight or obesity. miRNAs were analyzed using TaqMan Array miRNA Cards and normalized to the geometric mean of spiked-in ath-miR-159a and U6 small nuclear RNA using the ΔCT method. RESULTS: The average weight loss was 5.7 kg (P < 0.001). miR-122-5p (-0.18 ± 0.06 log fold relative to initial, P < 0.01) and miR-193a-5p (-0.12 ± 0.04, P < 0.01) levels decreased in response to weight loss. miR-126a-3p (0.11 ± 0.04, P = 0.01) and miR-222-3p (1.51 ± 0.12, P < 0.001) levels increased. Furthermore, a higher level of miR-122-5p was observed at baseline in participants with the metabolic syndrome compared with participants without (0.28 ± 0.08, P < 0.01). CONCLUSIONS: Changes in circulating miR-122-5p, miR-126a-3p, miR-193a-5p, and miR-222-3p in response to diet-induced weight loss are demonstrated. Furthermore, assessment of miR-122-5p could be an indicator of an adverse metabolic health status independent of obesity.


Assuntos
Síndrome Metabólica/genética , MicroRNAs/metabolismo , Obesidade/genética , Perda de Peso/genética , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Arterioscler Thromb Vasc Biol ; 40(4): 914-928, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32078363

RESUMO

OBJECTIVE: Systemic low-grade inflammation associated with obesity and metabolic syndrome is a strong risk factor for the development of diabetes mellitus and associated cardiovascular complications. This inflammatory state is caused by release of proinflammatory cytokines by macrophages, especially in adipose tissue. Long noncoding RNAs regulate macrophage activation and inflammatory gene networks, but their role in macrophage dysfunction during diet-induced obesity has been largely unexplored. Approach and Results: We sequenced total RNA from peritoneal macrophages isolated from mice fed either high-fat diet or standard diet and performed de novo transcriptome assembly to identify novel differentially expressed mRNAs and long noncoding RNAs. A top candidate long noncoding RNA, macrophage inflammation-suppressing transcript (Mist), was downregulated in both peritoneal macrophages and adipose tissue macrophages from high-fat diet-fed mice. GapmeR-mediated Mist knockdown in vitro and in vivo upregulated expression of genes associated with immune response and inflammation and increased modified LDL (low-density lipoprotein) uptake in macrophages. Conversely, Mist overexpression decreased basal and LPS (lipopolysaccharide)-induced expression of inflammatory response genes and decreased modified LDL uptake. RNA-pull down coupled with mass spectrometry showed that Mist interacts with PARP1 (poly [ADP]-ribose polymerase-1). Disruption of this RNA-protein interaction increased PARP1 recruitment and chromatin PARylation at promoters of inflammatory genes, resulting in increased gene expression. Furthermore, human orthologous MIST was also downregulated by proinflammatory stimuli, and its expression in human adipose tissue macrophages inversely correlated with obesity and insulin resistance. CONCLUSIONS: Mist is a novel protective long noncoding RNA, and its loss during obesity contributes to metabolic dysfunction and proinflammatory phenotype of macrophages via epigenetic mechanisms.


Assuntos
Inflamação/fisiopatologia , Ativação de Macrófagos/genética , Obesidade/genética , Obesidade/fisiopatologia , RNA Longo não Codificante/fisiologia , Tecido Adiposo/metabolismo , Animais , Linhagem Celular , LDL-Colesterol/metabolismo , Cromatina/genética , Citocinas/fisiologia , Regulação para Baixo , Humanos , Metabolismo dos Lipídeos/genética , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/fisiopatologia , Camundongos Endogâmicos C57BL , Poli(ADP-Ribose) Polimerase-1/genética , Poli ADP Ribosilação , Regulação para Cima
16.
PLoS One ; 15(1): e0227357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910446

RESUMO

Metabolic syndrome (MetS) which is caused by obesity and insulin resistance, is well known for its predictive capability for the risk of type 2 diabetes mellitus and cardiovascular disease. The development of MetS is associated with multiple genetic factors, environmental factors and lifestyle. We performed a genome-wide association study to identify single-nucleotide polymorphism (SNP) related to MetS in large Korean population based samples of 1,362 subjects with MetS and 6,061 controls using the Axiom® Korean Biobank Array 1.0. We replicated the data in another sample including 502 subjects with MetS and 1,751 controls. After adjusting for age and sex, rs662799 located in the APOA5 gene were significantly associated with MetS. 15 SNPs in GCKR, C2orf16, APOA5, ZPR1, and BUD13 were associated with high triglyceride (TG). 14 SNPs in APOA5, ALDH1A2, LIPC, HERPUD1, and CETP, and 2 SNPs in MTNR1B were associated with low high density lipoprotein cholesterol (HDL-C) and high fasting blood glucose respectively. Among these SNPs, 6 TG SNPs: rs1260326, rs1260333, rs1919127, rs964184, rs2075295 and rs1558861 and 11 HDL-C SNPs: rs4775041, rs10468017, rs1800588, rs72786786, rs173539, rs247616, rs247617, rs3764261, rs4783961, rs708272, and rs7499892 were first discovered in Koreans. Additional research is needed to confirm these 17 novel SNPs in Korean population.


Assuntos
HDL-Colesterol/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome Metabólica/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Glicemia/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Genótipo , Humanos , Resistência à Insulina/genética , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologia , Polimorfismo de Nucleotídeo Único
17.
Cardiovasc Pathol ; 46: 107192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31927390

RESUMO

BACKGROUND: Cytoplasmic fatty acid-binding proteins facilitate the transport of lipids to specific compartments in cells. Fatty acid-binding protein 4 (FABP4), also known as aP2 or A-FABP, plays a key role in the development of atherosclerosis, insulin resistance, obesity, and metabolic syndrome (MS). The FABP4 polymorphisms are associated with protein expression changes in vitro and metabolic and vascular alterations in vivo. The aim of this study was to investigate the association between FABP4 messenger ribonucleic acid (mRNA) expression levels in epicardial (EAT), pericardial (PAT), and subcutaneous adipose tissues (SAT), and the extent of coronary atherosclerosis in coronary artery disease (CAD) patients with MS. Furthermore, the relationship between the extent of coronary atherosclerosis and epicardial adipose tissue volume (EATV) and FABP4 gene variations was evaluated. PATIENTS AND METHODS: A total of 37 patients undergoing coronary artery bypass grafting because of CAD (MS CAD group) and 23 non-MS patients undergoing heart valve surgery (control group) were included. Coronary angiography was performed for all patients and the extent of coronary atherosclerosis was assessed using the Sullivan's scoring system. The mRNA expression levels of FABP4 gene in EAT, PAT, and SAT, and FABP4 polymorphisms were analyzed using the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: An increased FABP4 expression was observed in EAT and PAT of MS CAD group compared to controls. In the MS CAD group, FABP4 mRNA expression levels in EAT was 2.8-fold higher compared to PAT. The expression of FABP4 in EAT was positively correlated with the extent of atherosclerosis and EATV in MS CAD group (r = 0.588, P= 0.001, r = 0.174, P = 0.001, respectively). There were no correlations between PAT and SAT versus the extent of atherosclerosis and EATV. The FABP4 EAT mRNA expression levels were found to significantly increase in mutant allele carriers of rs1054135, whereas they significantly decreased in mutant allele carriers of rs77878271 (T-87C) in MS CAD group (P < 0.05). The extent of atherosclerosis was also found to be significantly associated with rs1054135 (P < 0.05). A cut-off point of 57.5 cm3 EATV was used indicating the presence of CAD with a significant area under the curve of 0.783%, 98% sensitivity, and 100% specificity (95% CI 0.620-0.880; P < 0.05). CONCLUSIONS: Our study results suggest that FABP4 expression in EAT is strongly associated with the extent of atherosclerosis and EATV in MS CAD patients.


Assuntos
Doença da Artéria Coronariana/genética , Proteínas de Ligação a Ácido Graxo/genética , Gordura Intra-Abdominal/química , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Gordura Subcutânea/química , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Predisposição Genética para Doença , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Síndrome Metabólica/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Fenótipo , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Índice de Gravidade de Doença , Gordura Subcutânea/diagnóstico por imagem
19.
Arterioscler Thromb Vasc Biol ; 40(3): 611-623, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31941380

RESUMO

OBJECTIVE: We tested the hypothesis that enlarged, dysfunctional HDL (high-density lipoprotein) particles contribute to the augmented atherosclerosis susceptibility associated with SR-BI (scavenger receptor BI) deficiency in mice. Approach and Results: We eliminated the ability of HDL particles to fully mature by targeting PLTP (phospholipid transfer protein) functionality. Particle size of the HDL population was almost fully normalized in male and female SR-BI×PLTP double knockout mice. In contrast, the plasma unesterified cholesterol to cholesteryl ester ratio remained elevated. The PLTP deficiency-induced reduction in HDL size in SR-BI knockout mice resulted in a normalized aortic tissue oxidative stress status on Western-type diet. Atherosclerosis susceptibility was-however-only partially reversed in double knockout mice, which can likely be attributed to the fact that they developed a metabolic syndrome-like phenotype characterized by obesity, hypertriglyceridemia, and a reduced glucose tolerance. Mechanistic studies in chow diet-fed mice revealed that the diminished glucose tolerance was probably secondary to the exaggerated postprandial triglyceride response. The absence of PLTP did not affect LPL (lipoprotein lipase)-mediated triglyceride lipolysis but rather modified the ability of VLDL (very low-density lipoprotein)/chylomicron remnants to be cleared from the circulation by the liver through receptors other than SR-BI. As a result, livers of double knockout mice only cleared 26% of the fractional dose of [14C]cholesteryl oleate after intravenous VLDL-like particle injection. CONCLUSIONS: We have shown that disruption of PLTP-mediated HDL maturation reduces SR-BI deficiency-driven atherosclerosis susceptibility in mice despite the induction of proatherogenic metabolic complications in the double knockout mice.


Assuntos
Aterosclerose/prevenção & controle , HDL-Colesterol/sangue , Metabolismo Energético , Fígado/metabolismo , Síndrome Metabólica/sangue , Proteínas de Transferência de Fosfolipídeos/deficiência , Receptores Depuradores Classe B/deficiência , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Ésteres do Colesterol/administração & dosagem , Ésteres do Colesterol/sangue , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/genética , Hipertrigliceridemia/sangue , Hipertrigliceridemia/genética , Masculino , Síndrome Metabólica/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/sangue , Obesidade/genética , Proteínas de Transferência de Fosfolipídeos/genética , Placa Aterosclerótica , Receptores Depuradores Classe B/genética
20.
Biochim Biophys Acta Gene Regul Mech ; 1863(4): 194396, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31271897

RESUMO

Maternally Expressed Gene 3 (MEG3) is a long noncoding RNA (lncRNA) that coordinates a diverse array of cellular processes requiring epigenetic regulation of genes and interactions with key signaling proteins and by acting as a competitive endogenous (ce)RNA. Epigenetic modifications driven by in utero nutrition affect MEG3 expression and its role in the development of multiple metabolic disorders. This review examines how epigenetic modification of MEG3 expression can confer adaptedness to different metabolic environments. To this end, we discuss how nutritional status that leads to an increase of MEG3 expression can protect against cancer and metabolic dysfunctions, while interventions that promote MEG3 downregulation minimize the pleiotropic costs associated with its expression. Lastly, we identify research directions that would further shed light on the role of MEG3 in metabolic regulation and in functional imprinted gene networks. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen.


Assuntos
RNA Longo não Codificante/metabolismo , Epigênese Genética , Regulação da Expressão Gênica , Genes Supressores de Tumor , Humanos , Síndrome Metabólica/genética , Neoplasias/genética , Neoplasias/metabolismo , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética
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