RESUMO
OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.
Assuntos
Cirurgia Bariátrica , Obesidade Metabolicamente Benigna , Feminino , Masculino , Humanos , Espessura Intima-Media Carotídea , Fator A de Crescimento do Endotélio Vascular , Estudos de Casos e Controles , Fatores de Risco , Obesidade Metabolicamente Benigna/metabolismo , Obesidade/metabolismoRESUMO
The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be "metabolically healthy". Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.
Assuntos
Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade Metabolicamente Benigna/epidemiologia , Obesidade/epidemiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Glucocorticoides/metabolismo , Humanos , Gordura Intra-Abdominal/metabolismo , Lipase/genética , Lipogênese , Proteínas de Membrana/genética , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Obesidade Metabolicamente Benigna/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
Obesity is not the same in all individuals and two different phenotypes have been described: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The aim of this study was to identify factors that explain metabolic health status in a rigorously matched Spanish population. Subcutaneous and visceral fat, adipocyte size and fatty acid composition, cardiometabolic markers in serum, and lifestyle habits were assessed. Higher physical activity in the mornings (Odds Ratio (95% Confidence Interval) (OR (95% CI) = 1.54 (1.09-2.18), p = 0.01)), earlier bedtimes (8:30-10:30 pm) (OR = 2.11 (1.02-4.36), p = 0.04), a complete breakfast (OR = 1.59 (1.07-2.36), p = 0.02), and a greater number of meals per day (4.10 ± 0.05 vs. 3.93 ± 0.05, p < 0.01), were associated with the MHO phenotype. Concentrations of 20:5 n-3 eicosapentaenoic acid (0.26 ± 0.46 vs. 0.10% ± 0.11%, p = 0.04) and 18:3 n-6 gamma-linolenic acid (0.37 ± 0.24 vs. 0.23% ± 0.22%, p = 0.04) in subcutaneous adipocytes were higher and omental adipocyte size (187 094 ± 224 059 µm3 vs. 490 953 ± 229 049 µm3, p = 0.02) was lower in MHO subjects than in those with MUO. Visceral fat area differed between MHO and MUO subjects (135 ± 60 cm2 vs. 178 ± 85 cm2, p = 0.04, respectively). The study highlights specific lifestyle habits that could form part of obesity therapies, not only involving healthier eating habits but also earlier sleeping and exercise patterns.
Assuntos
Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Obesidade Metabolicamente Benigna/fisiopatologia , Obesidade/fisiopatologia , Sono/fisiologia , Adipócitos/patologia , Tecido Adiposo Branco/química , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Adulto , Tamanho Celular , Ritmo Circadiano/fisiologia , Estudos Transversais , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/patologia , Obesidade Metabolicamente Benigna/metabolismo , Obesidade Metabolicamente Benigna/patologiaRESUMO
Considering the inadequacy of some antioxidant nutrients in severely obese adolescents, this study aimed to assess the relationship between antioxidant micronutrients status and metabolic syndrome components in metabolically healthy obesity (MHO) and unhealthy obesity (MUO). We performed an observational study in severely obese adolescents (body mass index > 99th percentile) and they were classified into MHO or MUO, according to the criteria adapted for adolescents. Anthropometric, biochemical, and clinical variables were analyzed to characterize the sample of adolescents. The serum antioxidant nutrients assessed were retinol, ß-carotene, Vitamin E, Vitamin C, zinc and selenium. A total of 60 adolescents aged 17.31 ± 1.34 years were enrolled. MHO was identified in 23.3% of adolescents. The MHO group showed lower frequency of non-alcoholic fatty liver disease (14.3% vs. 78.3%, p < 0.001) when compared to MUO. A correlation was found between retinol and ß-carotene concentrations with glycemia (r = -0.372; p = 0.011 and r = -0.314; p = 0.034, respectively) and between Vitamin E with waist circumference (r = -0.306; p = 0.038) in the MUO group. The current study shows that some antioxidant nutrients status, specifically retinol, ß-carotene, and Vitamin E, are negatively associated with metabolic alterations in MUO. Further studies are necessary to determine the existing differences in the serum antioxidant profile of metabolically healthy and unhealthy obese adolescents.
Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Estado Nutricional , Obesidade Metabolicamente Benigna/metabolismo , Obesidade Mórbida/metabolismo , Estresse Oxidativo , Obesidade Infantil/metabolismo , Adolescente , Índice de Massa Corporal , Brasil/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Metabolicamente Benigna/sangue , Obesidade Metabolicamente Benigna/fisiopatologia , Obesidade Mórbida/sangue , Obesidade Mórbida/fisiopatologia , Obesidade Infantil/sangue , Obesidade Infantil/fisiopatologia , Prevalência , Fatores de Risco , Selênio/sangue , Índice de Gravidade de Doença , Vitaminas/sangue , Circunferência da Cintura , Zinco/sangueRESUMO
BACKGROUND: Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. METHODS AND RESULTS: We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P<0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P<0.0001). CONCLUSIONS: Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status.
Assuntos
Endotélio Vascular/fisiopatologia , Dedos/irrigação sanguínea , Síndrome Metabólica/fisiopatologia , Microvasos/fisiopatologia , Obesidade Metabolicamente Benigna/fisiopatologia , Adulto , Idoso , Índice de Massa Corporal , Brasil/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Manometria , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade Metabolicamente Benigna/metabolismo , Sobrepeso/epidemiologia , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Fluxo Pulsátil , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
UNLABELLED: Background. This study aims to identify key genes and pathways involved in non-alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: The dataset GSE48452 was downloaded from Gene Expression Omnibus, including 14 control liver samples, 27 healthy obese samples, 14 steatosis samples and 18 nonalcoholic steatohepatitis (NASH) samples. Differentially expressed genes (DEGs) between controls and other samples were screened through LIMMA package. Then pathway enrichment analysis for DEGs was performed by using DAVID, and alterations of enriched pathways were determined. Furthermore, protein-protein interaction (PPI) networks were constructed based on the PPI information from HPRD database, and then, networks were visualized through Cytoscape. Additionally, interactions between microRNAs (miRNAs) and pathways were analyzed via Fisher's exact test. RESULTS: A total of 505, 814 and 783 DEGs were identified for healthy obese, steatosis and NASH samples in comparison with controls, respectively. DEGs were enriched in ribosome (RPL36A, RPL14, etc.), ubiquitin mediated proteolysis (UBE2A, UBA7, etc.), focal adhesion (PRKCA, EGFR, CDC42, VEGFA, etc.), Fc?R-mediated phagocytosis (PRKCA, CDC42, etc.), and so on. The 27 enriched pathways gradually deviated from baseline (namely, controls) along with the changes of obese-steatosis-NASH. In PPI networks, PRKCA interacted with EGFR and CDC42. Besides, hsa-miR-330-3p and hsa-miR-126 modulated focal adhesion through targeting VEGFA and CDC42. CONCLUSIONS: The identified DEGs (PRKCA, EGFR, CDC42, VEGFA), disturbed pathways (ribosome, ubiquitin mediated proteolysis, focal adhesion, Fc?R-mediated phagocytosis, etc.) and miRNAs (hsa-miR-330-3p, hsa-miR-126, etc.) might be closely related to NAFLD progression. These results might contribute to understanding NAFLD mechanism, conducting experimental researches, and designing clinical practices.
Assuntos
Hepatopatia Gordurosa não Alcoólica/genética , Obesidade Metabolicamente Benigna/genética , Adulto , Idoso , Estudos de Casos e Controles , Bases de Dados Genéticas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Adesões Focais/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Redes e Vias Metabólicas , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Metabolicamente Benigna/metabolismo , Fagocitose/genética , Mapas de Interação de Proteínas , Proteína Quinase C-alfa/genética , Proteína Quinase C-alfa/metabolismo , Proteólise , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismoRESUMO
OBJECTIVE: The aim of this study was to identify metabolically healthy obese individuals (MHOs) and their characteristics, as well as to estimate cardiovascular risk using the Framingham score. METHOD: In all, 258 adult individuals, with body mass index ≥30 kg/m(2), and no report of diabetes mellitus or cardiovascular disease, were classified according to their metabolic state considering two criteria: rhe National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and the homeostasis model assessment (HOMA). Biochemical, anthropometric, and body composition characteristics were compared between MHOs and metabolically unhealthy obese (MUO) individuals according to each criterion. Cardiovascular risk was estimated using the Framingham score. RESULTS: MHOs exhibited smaller waist circumference and lower body fat percentage, as well as lower blood glucose, triacylglycerols, and insulin levels, in addition to higher high-density lipoprotein cholesterol concentration, when HOMA criterion (P < 0.05) and associated criteria were adopted. The estimated cardiovascular risk was similar between the two groups according to the HOMA index; however, the risk was significantly lower according to the ATP III guidelines. Obese individuals at intermediate and high risk showed higher body fat percentage compared with those individuals at low risk. CONCLUSIONS: MHOs had biochemical and anthropometric characteristics, such as lower body mass index, waist circumference, percent fat mass, glucose, triacylglycerols, and increased high-density lipoprotein, that made them different from those individuals classified as MUO. The latter exhibited increased risk for cardiovascular disease according to the Framingham score, when using the ATP III criterion alone or in conjunction with the HOMA index.