RESUMO
Muscle atrophy is closely associated with many diseases, including diabetes and cardiac failure. Growing evidence has shown that mitochondrial dysfunction is related to muscle atrophy; however, the underlying mechanisms are still unclear. To elucidate how mitochondrial dysfunction causes muscle atrophy, we used hindlimb-immobilized mice. Mitochondrial function is optimized by balancing mitochondrial dynamics, and we observed that this balance shifted towards mitochondrial fission and that MuRF1 and atrogin-1 expression levels were elevated in these mice. We also found that the expression of yeast mitochondrial escape 1-like ATPase (Yme1L), a mitochondrial AAA protease was significantly reduced both in hindlimb-immobilized mice and carbonyl cyanide m-chlorophenylhydrazone (CCCP)-treated C2C12 myotubes. When Yme1L was depleted in myotubes, the short form of optic atrophy 1 (Opa1) accumulated, leading to mitochondrial fragmentation. Moreover, a loss of Yme1L, but not of LonP1, activated AMPK and FoxO3a and concomitantly increased MuRF1 in C2C12 myotubes. Intriguingly, the expression of myostatin, a myokine responsible for muscle protein degradation, was significantly increased by the transient knock-down of Yme1L. Taken together, our results suggest that a deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, which contribute to the pathological state of muscle atrophy.
Assuntos
Proteína Forkhead Box O3/metabolismo , Metaloendopeptidases/antagonistas & inibidores , Mitocôndrias/patologia , Proteínas Mitocondriais/antagonistas & inibidores , Atrofia Muscular/patologia , Miostatina/metabolismo , Animais , Regulação para Baixo , Proteína Forkhead Box O3/genética , Masculino , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Miostatina/genéticaRESUMO
This study aimed to validate body composition analysis using bioelectrical impedance analysis (BIA) against dual-energy X-ray absorptiometry (DXA) in children with obesity and to compare agreement between BIA and DXA according to their degree of obesity. Three hundred and sixteen children aged 6-17 years participated in the Intervention for Childhood and Adolescents Obesity via Activity and Nutrition study. We divided participants by body mass index (BMI) percentile (group 1: mild to moderate obesity; group 2: severe obesity) and compared body composition variables, eg, percentage of body fat (%BF), fat mass (FM), and fat-free mass (FFM) using BIA and DXA. The %BF and FM of BIA were significantly lower (-1.8% and -0.8 kg, respectively), and the FFM of BIA was significantly higher (1.4 kg) than those of DXA. There were significant negative relationships between the absolute value of differences from BIA and DXA and BMI z-scores in %BF, FM, and FFM (regression coefficient [ß]: -1.39, 95% confidence interval [CI]: -1.81 to -0.97; ß: -0.34, 95%CI: -0.61 to -0.06; ß: -0.73, 95%CI: -1.03 to -0.44, respectively). The gap of body compositions between BIA and DXA decreased as participants became more obese, and the differences of FM in boys with severe obesity and the differences of %BF and FFM in girls with severe obesity were much less than those in children with mild to moderate obesity. In conclusion, the agreement between DXA and BIA was better for children with severe obesity than for children with mild to moderate obesity.
Assuntos
Composição Corporal , Impedância Elétrica , Obesidade Mórbida/fisiopatologia , Obesidade Infantil/fisiopatologia , Absorciometria de Fóton , Adiposidade , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: A low serum level of high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 5 (PCSK5) modulates HDL-C metabolism through the inactivation of endothelial lipase activity. METHODS: Therefore, we analysed the effects of PCSK5 on HDL-C and investigated the association between genetic variation in PCSK5 and dietary polyunsaturated fatty acids (PUFAs) intakes in Korean adults and children. This population-based study which was conducted in South Korea included 4205 adults (43% male) aged 40-69â years and 1548 children (48.6% boys) aged 8-13â years. Dietary intake was assessed using a semiquantitative food frequency questionnaire in adults and modified 3-day food records in children. RESULTS: After adjustments for age and body mass index, we identified a significant association between SNP rs1029035 of the PCSK5 gene and HDL-C concentrations specifically for men in both populations (adults, p=0.004; children, p=0.003; meta, p=7×10(-4)). Additionally, the interaction between the PCSK5 rs1029035 genotype and dietary polyunsaturated fatty acids intake influenced serum HDL-C concentrations in men (adults, p=0.001; children, p=0.008). The deleterious effect of the C allele on serum HDL-C was present only when dietary PUFA intake was less than the dichotomised median level (adults, p=0.011; children, p=0.001). Serum HDL-C concentrations were decreased in men with the C allele genotype and low consumption of dietary PUFA including n-3 and n-6. CONCLUSION: According to these results, men carrying of the C allele were associated with low HDL-C concentrations and might exert beneficial effects on HDL-C concentrations following consumption of a high-PUFA diet.
Assuntos
HDL-Colesterol/genética , Dieta , Ácidos Graxos Insaturados/metabolismo , Variação Genética , Adulto , Idoso , Criança , Ingestão de Energia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Pró-Proteína Convertase 5 , República da CoreiaRESUMO
We recently reported that glutamate carboxypeptidase II (GCPII) has a new physiological function degrading amyloid-ß (Aß), distinct from its own hydrolysis activity in N-acetyl-L-aspartyl-L-glutamate (NAAG); however, its underlying mechanism remains undiscovered. Using site-directed mutagenesis and S1 pocket-specific chemical inhibitor (compound 2), which was developed for the present study based on in sillico computational modeling, we discovered that the Aß degradation occurs through S1 pocket but not through S1' pocket responsible for NAAG hydrolysis. Treatment with compound 2 prevented GCPII from Aß degradation without any impairment in NAAG hydrolysis. Likewise, 2-PMPA (specific GCPII inhibitor developed targeting S1' pocket) completely blocked the NAAG hydrolysis without any effect on Aß degradation. Pre-incubation with NAAG and Aß did not affect Aß degradation and NAAG hydrolysis, respectively. These data suggest that GCPII has two distinctive binding sites for two different substrates and that Aß degradation occurs through binding to S1 pocket of GCPII.
Assuntos
Doença de Alzheimer/enzimologia , Peptídeos beta-Amiloides/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Proteólise , Doença de Alzheimer/metabolismo , Animais , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Dipeptídeos/metabolismo , Inibidores Enzimáticos/farmacologia , Glutamato Carboxipeptidase II/antagonistas & inibidores , Glutamato Carboxipeptidase II/química , Glutamato Carboxipeptidase II/genética , Ácido Glutâmico/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Compostos Organofosforados/farmacologia , Proteólise/efeitos dos fármacosRESUMO
BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of ß2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-ß2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-ß2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION: This is the first discovery of a new target molecule of NO, ß2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-ß2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.
Assuntos
Infarto do Miocárdio , Miócitos Cardíacos , Animais , Camundongos , Tubulina (Proteína) , Diferenciação Celular , Recuperação de Função Fisiológica , Infarto do Miocárdio/terapia , MicrotúbulosRESUMO
Liver fibrosis is a common consequence of various chronic liver injuries, including virus infection and ethanol. Activated hepatic stellate cells (HSCs) contribute to liver fibrosis through the accumulation of extracellular matrix proteins, including type I alpha collagen (COL1A). The activation of adenosine monophosphate-activated protein kinase (AMPK) modulates HSCs activation, but its underlying mechanism remains unclear. Here, we report that AMPK inhibits transforming growth factor (TGF)-ß-induced fibrogenic property of HSCs by regulating transcriptional coactivator p300. We treated human (LX-2) and rat (CFSC-2G) HSC lines with TGF-ß to induce fibrogenic activation of HSCs. Pharmacological activation of AMPK by treatment with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), metformin, or adiponectin lowered TGF-ß-induced expression of COL1A and myofibroblast marker alpha-smooth muscle actin (α-SMA). Transient transduction of constitutively active AMPKα (caAMPKα) was sufficient to attenuate COL1A and α-SMA expression, whereas an AMPK inhibitor considerably abrogated the inhibitory effect of AICAR on fibrogenic gene expression. Although AMPK significantly suppressed Smad-dependent transcription, it did not affect TGF-ß-stimulated phosphorylation, nuclear localization, or DNA-binding activity of Smad2/3. AICAR rather attenuated TGF-ß-induced Smad3 interaction with transcriptional coactivator p300 accompanying with reduction of Smad3 acetylation. Moreover, AICAR induced not only physical interaction between AMPK and p300 but also proteasomal degradation of p300 protein. Our data provide substantial evidence that AMPK could be a novel therapeutic target for treatment of liver fibrosis, by demonstrating the underlying mechanism of AMPK-induced antifibrotic function in HSCs.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteína p300 Associada a E1A/metabolismo , Células Estreladas do Fígado/enzimologia , Cirrose Hepática/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Linhagem Celular Transformada , Marcação de Genes , Células Estreladas do Fígado/citologia , Humanos , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Ratos , Fator de Crescimento Transformador beta1/fisiologiaRESUMO
Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (-503/-498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Receptores Virais/biossíntese , Elementos de Resposta , Fator de Transcrição Sp1/metabolismo , Proteínas Supressoras de Tumor/biossíntese , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus , Células Hep G2 , Inibidores de Histona Desacetilases/farmacologia , Humanos , Neoplasias/patologiaRESUMO
BACKGROUND: There have been lots of studies about the relationship between chronic use of alcohol and the development of type 2 diabetes mellitus (T2DM). Chronic use of alcohol can be affected by the altered level of ghrelin and leptin which regulate food-seeking behavior having similar mechanism of controlling alcohol-craving behavior. Those peptides are known to be correlated with T2DM. Ghrelin and leptin also have been regarded as possible regulators of glucose metabolism and insulin function. Hence, there is the possibility that ghrelin and leptin can be related with deteriorated pathophysiology of T2DM in alcoholic patients. METHODS: Patients with alcohol dependence diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) underwent an 75 g oral glucose-tolerance test (OGTT), to classify them to normal glucose tolerance (NGT, n = 52), pre-diabetes including impaired glucose tolerance (IGT), impaired fasting glucose level (IFG) and combination of IGT and IFG (Pre-DM, n = 26) and T2DM (n = 24) groups. Fasting plasma ghrelin and leptin levels were compared among groups. RESULTS: There was no difference of ghrelin concentration among the groups but the leptin concentration was significantly different between NGT and T2DM group (p < 0.05). Increased leptin levels were significantly correlated with body mass index (BMI), insulin level, and insulin resistance. CONCLUSIONS: Chronic alcohol drinking might produce leptin resistance which makes leptin significantly correlated with fasting insulin concentration and insulin resistance. Therefore, we suppose that increased level of leptin by chronic alcohol use could be one of the main mechanisms that develop insulin resistance in alcoholic patients.
Assuntos
Alcoolismo/sangue , Diabetes Mellitus Tipo 2/sangue , Grelina/sangue , Leptina/sangue , Alcoolismo/complicações , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is one of the strongest susceptibility genes for type 2 diabetes mellitus (T2DM). Association studies between KCNQ1 genetic variants and T2DM have been reported. The multifactorial disease T2DM is caused by interactions between genetic susceptibility and environmental factors. In this study, we examined the associations between the KCNQ1 haplotype, which consists of the major alleles rs3852528, rs11024175, and rs2237892 (ht: ACC), and environmental factors such as alcohol consumption, which are related to the risk of T2DM, in two independent Korean populations. Data from health examination studies, i.e., HEXA (n = 50,357 subjects) and the Ansung-Ansan community-based Korean cohort study (n = 7603), were analyzed. In both cohorts, fasting blood glucose levels were significantly increased in moderate-to-heavy drinkers and carriers of the homozygous ACC haplotype. A significant association between the KCNQ1 haplotype and alcohol consumption in the risk of diabetes was observed in the HEXA (OR 1.587; 95% CI 1.128-2.234) and Ansung-Ansan (OR 2.165; 95% CI 1.175-3.989) cohorts compared with abstainers not carrying the KCNQ1 haplotype. Associations of the KCNQ1 haplotype with alcohol consumption and ß-cell function were observed in the Ansung-Ansan cohort. Moderate-to-heavy drinkers with the ACC haplotype had lower fasting insulin levels and mean 60 min insulinogenic index (IGI60) compared with light drinkers and abstainers not carrying the ACC haplotype. These findings indicate that KCNQ1 variants play a synergistic role with alcohol consumption in the development of T2DM and impaired ß-cell function.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Diabetes Mellitus Tipo 2/etiologia , Canal de Potássio KCNQ1/genética , Alcoolismo/complicações , Alelos , Glicemia/análise , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , República da CoreiaRESUMO
Chronic alcohol consumption is known to be associated with type 2 diabetes (T2D), which is developed by two underlying mechanisms, ß-cell dysfunction and insulin resistance. Identification of genetic variants in association with the development of T2D may help explain the genetic risk factors of T2D. In this study, we tried to find out some genetic variations, which interact with alcohol consumption and also are associated with ß-cell function through 12 year's follow-up study in Korean population. We performed a genotype association study using the community-based Ansung-Ansan Cohort data (baseline n = 3120; follow-up n = 433). Genotype association analyses of the baseline data showed that alcohol consumption is associated with the decreases of blood insulin levels and insulin secretion in participants with the KCNJ11 rs5219 risk allele. Moreover, multivariate logistic regression analyses revealed that the risk allele group is vulnerable to impairment of ß-cell function in response to alcohol consumption (OR 1.450; 95% CI 1.061-1.982). Furthermore, 12-year' follow-up results showed that alcohol consumption synergistically decreases insulin secretion in participants with KCNJ11 rs5219 risk alleles. Our findings demonstrate that the KCNJ11 rs5219 risk allele in combination with alcohol consumption could be a potential risk factor of ß-cell dysfunction. We hope that this new findings could be helpful to further understand the development of T2D depending on individual genetic background in association with alcohol consumption.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Polimorfismo de Nucleotídeo Único , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Povo Asiático/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologiaRESUMO
SCOPE: Accumulating evidence indicates that micronutrients are related to metabolic diseases. However, comparatively less attention has been devoted to their influence on each other during the development of metabolic diseases. To investigate the underlying mechanisms, the effects of iron and vitamin D on pancreatic ß cell functions are examined. METHODS AND RESULTS: Iron overload is induced in INS-1 rat insulinoma pancreatic ß cells and it is found that iron overload dramatically reduce expression of the vitamin D receptor (VDR). Iron overload-induced ß cell dysfunction is rescued by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) cotreatment via restoration of VDR level and the consequent maintenance of Ca2+ homeostasis. Iron accumulation is also observed in the islets of 22-month-old C57BL/6 mice fed with a chow diet (1000 IU vitamin D3 per kg). In contrast, islet iron accumulation and hyperinsulinemia are ameliorated in mice fed with a vitamin D3 -supplemented diet (20 000 IU kg-1 ). CONCLUSION: The authors show that functional failure of ß cells due to iron accumulation is rescued by 1,25(OH)2 D3 , and iron overload significantly reduces VDR levels in ß cells. These results suggest that iron and vitamin D inversely influence pancreatic ß cell function.
Assuntos
Cálcio/metabolismo , Colecalciferol/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Sobrecarga de Ferro/patologia , Receptores de Calcitriol/metabolismo , Animais , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular , Homeostase/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Ferro/metabolismo , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Ratos , Vitamina D/análogos & derivados , Vitamina D/farmacologiaRESUMO
OBJECTIVE: We aimed to assess the effectiveness of the first 6 months of a 24 month multidisciplinary intervention program including circuit training and a balanced diet in children and adolescents with obesity. METHODS: A quasi-experimental intervention trial included 242 participants (age [mean±standard deviation]: 11.3±2.06 years, 97 girls) of at least 85th percentile of age- and sex-specific body mass index (BMI). Participants were grouped into three to receive usual care (usual care group), exercise intervention with circuit training (exercise group), or intensive nutritional and feedback intervention with a balanced diet (nutritional group). Primary outcome was BMI z-score, while secondary outcomes included body composition, cardiometabolic risk markers, nutrition, and physical fitness. RESULTS: Among the participants, 80.6% had a BMI ≥ the 97th percentile for age and sex. The BMI z-score of the overall completers decreased by about 0.080 after 6 months of intervention (p < 0.001). After the intervention, both exercise and nutritional groups had significantly lower BMI z-scores than the baseline data by about 0.14 and 0.075, respectively (p < 0.05). Significant group by time interaction effects were observed between exercise versus usual care group in BMI z-score (ß, -0.11; 95% confidence interval (CI), -0.20 to -0.023) and adiponectin (ß, 1.31; 95% CI, 1.08 to 1.58); and between nutritional versus usual care group in waist circumference (ß, -3.47; 95% CI, -6.06 to -0.89). No statistically significant differences were observed in any of the other secondary outcomes assessed. CONCLUSION: Multidisciplinary intervention including circuit training and a balanced diet for children and adolescents with obesity reduced the BMI z-score and improved cardiometabolic risk markers such as adiponectin and waist circumference.
Assuntos
Dieta Redutora/métodos , Terapia por Exercício/métodos , Síndrome Metabólica/terapia , Obesidade/terapia , Adiponectina/sangue , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Síndrome Metabólica/dietoterapia , Obesidade/dietoterapiaRESUMO
Unhealthy dietary patterns are associated with obesity in children and adolescents. However, few studies have investigated the relationships between dietary patterns and obesity-related metabolic disorders among Asians. We identified dietary patterns in children and adolescents and examined the associations between these patterns and obesity, insulin resistance, and metabolic syndrome in South Korea. This study is a cross-sectional design. We used baseline data from an intervention study of 435 Korean children and adolescents aged 6-17 years. Insulin resistance was assessed as HOMA-IR ≥ 2.6. Metabolic syndrome was diagnosed by cardiovascular disease risk factor clustering. Dietary intakes were estimated using 3-day food records. Factor analysis was used to obtain dietary patterns, and we examined the associations between dietary patterns and obesity-related markers adjusted for potential covariates. Three dietary patterns were identified as fast food and soda (FFS), white rice and kimchi (WRK), and oil and seasoned vegetable (OSV) patterns. Compared with participants in the lower intake of FFS pattern, those in the top intake were associated with a higher waist circumference (WC) (ß = 1.55), insulin level (ß = 1.25), and body mass index (BMI) (ß = 0.53) and it was positively associated with HOMA-IR ≥ 2.6 (OR = 2.11; 95% CI: 1.227-3.638) (p < 0.05). WRK pattern was associated with lower weight and higher HDL cholesterol, and the OSV pattern was associated with a lower weight, WC, and insulin level (p < 0.05). The FFS pattern showed a positive relation with WC, serum insulin, and BMI, and the other two dietary patterns indicated a preventive effect of those parameters. The FFS pattern was associated with significantly elevated insulin resistance among children and adolescents.
Assuntos
Peso Corporal , Doenças Metabólicas , Adolescente , Glicemia , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade Infantil , Fatores de Risco , Circunferência da CinturaRESUMO
Childhood obesity has increased worldwide, and many clinical and public interventions have attempted to reduce morbidity. We aimed to determine the metabolomic signatures associated with weight control interventions in children with obesity. Forty children from the "Intervention for Children and Adolescent Obesity via Activity and Nutrition (ICAAN)" cohort were selected according to intervention responses. Based on changes in body mass index z-scores, 20 were responders and the remaining non-responders. Their serum metabolites were quantitatively analyzed using capillary electrophoresis time-of-flight mass spectrometry at baseline and after 6 and 18 months of intervention. After 18 months of intervention, the metabolite cluster changes in the responders and non-responders showed a difference on the heatmap, but significant metabolites were not clear. However, regardless of the responses, 13 and 49 metabolites were significant in the group of children with obesity intervention at 6 months and 18 months post-intervention compared to baseline. In addition, the top five metabolic pathways (D-glutamine and D-glutamate metabolism; arginine biosynthesis; alanine, aspartate, and glutamate metabolism; TCA cycle (tricarboxylic acid cycle); valine, leucine, and isoleucine biosynthesis) including several amino acids in the metabolites of obese children after 18 months were significantly changed. Our study showed significantly different metabolomic profiles based on time post obesity-related intervention. Through this study, we can better understand and predict childhood obesity through metabolite analysis and monitoring.
RESUMO
Data on the association between alcohol consumption and the risk of type 2 diabetes mellitus (T2DM) have accumulated, but little has been reported about this association in terms of lean T2DM. The present study analyzed 10-year longitudinal data to investigate the association between alcohol consumption and T2DM risk among lean individuals. This prospective study included 2,366 male and female Koreans aged 40-69 years who were free of DM and had a body mass index (BMI) <23 kg/m2 during the baseline period between 2001 and 2012. Information on alcohol consumption, BMI, and incident cases of T2DM were identified by interviews and health examinations. To analyze the association between alcohol consumption and T2DM risk, Cox proportional hazard regression analysis was used. Alcohol drinkers consuming at least 16 g/day of alcohol (2 units/day) who maintained a BMI <23 kg/m2 over 10 years had a significantly higher T2DM risk even after controlling for BMI and potential risk factors. Compared with lifetime abstainers, multivariate hazard ratios (HR) [95% confidence interval] of T2DM were 1.74 [1.02, 2.95] for 16-30 g/day, 2.09 [1.16, 3.77] for 31-60 g/day, and 1.94 [1.07, 3.51] for >60g/day among alcohol drinkers. No protective effect of moderate alcohol consumption <16 g/day on T2DM risk was observed. Age, parental history of DM, and physical inactivity were also significant risk factors for lean T2DM. Alcohol consumption of at least 2 units/day increased T2DM risk among lean individuals. Abstaining from alcohol and physical activity may be beneficial for the prevention of lean T2DM.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Exercício Físico , Magreza/epidemiologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia , Caracteres SexuaisRESUMO
The discovery of metabolomics-based biomarkers has been a focus of recent kidney dysfunction research. In the present study, we aimed to identify metabolites associated with chronic kidney disease (CKD) in the general population using a cross-sectional study design. At baseline, 6.5% of subjects had CKD. Pearson correlation analysis showed that 28 metabolites were significantly associated with estimated glomerular filtration rate (eGFR) after Bonferroni correction. Among these metabolites, 4 acylcarnitines, 12 amino acids, 4 biogenic amines, 1 phosphatidylcholine, and 1 sphingolipid were associated with CKD (p < 0.05). After eight years, 13.5% of subjects had CKD. Three amino acid metabolites were positively associated with new-onset CKD: citrulline [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.26-4.59], kynurenine (OR: 1.98, 95% CI: 1.05-3.73), and phenylalanine (OR: 2.68, 95% CI: 1.00-7.16). The kynurenine:tryptophan ratio was also associated with CKD (OR: 3.20; 95% CI: 1.57-6.51). The addition of multiple metabolites significantly improved the CKD prediction by C statistics (0.756-0.85, p < 0.0001), and the net reclassification improvement was 0.84 (95% CI: 0.72-0.96). Elevated hs-C reactive protein (CRP) was associated with new-onset CKD (OR: 1.045, 95% CI: 1.005-1.086); however, this association disappeared following adjustment with the kynurenine:tryptophan ratio. The levels of citrulline and kynurenine and their ratio to tryptophan in CKD patients with proteinuria were worse than those with one or neither characteristic. Together, the results of this study demonstrate that amino acid metabolites are associated with CKD eight years after initial metabolite assessment. These results could improve the identification of subjects at high risk of CKD who have modified amino acid metabolism.
RESUMO
BACKGROUND/OBJECTIVES: Evidence-based customized nutritional interventions are required for effective treatment of moderate to severe obese children and adolescents. SUBJECTS/METHODS: Sixty six (64.1% of 103) of the eligible participants who joined the usual care or physical activity group in the clinic were involved in 16-week intervention. Customized nutritional intervention was implemented for each participant based on a nutrition care process (NCP) model. Sociodemographic assessment, anthropometrics data, health- and dietary-related behaviors, and dietary intake of the study subjects were assessed at baseline and follow-up. All participants engaged in 30-minute nutritional sessions on a monthly basis. RESULTS: After 16 weeks, there were significant improvements in body composition [BMI (-0.8 ± 0.9, P < 0.05), BMI z-score (-0.3 ± 0.2, P < 0.001), body fat (kg) (-1.3 ± 2.1, P < 0.05), and body fat (%)(-1.5 ± 1.9, P < 0.05)] as well as macronutrient intake [total energy intake (kcal) (-563.7 ± 656.8, P < 0.05), energy (%) (-26.5 ± 30.0, P < 0.05) and fat (g) (-28.3 ± 40.6, P < 0.05)] in the adherent group than the non-adherent group. The SOC was higher in both groups after the intervention (P < 0.001). CONCLUSIONS: Our results highlight the positive effects of an evidence-based approach as a multidisciplinary intervention for people-centered nutritional care and weight management.
RESUMO
BACKGROUND: Alcohol consumption is associated with hypertension, and this association depends on the alcohol consumption pattern and alcohol flushing response. In this 12-year follow-up study, we investigated the relationship between the alcohol consumption pattern and incidence of hypertension in the Korean population. METHODS: We analyzed 1,366 Korean participants in the Ansung-Ansan cohort study without hypertension at baseline. The subjects were classified into four alcohol consumption patterns: never-drinking, light alcohol consumption, moderate alcohol consumption, and heavy alcohol consumption, and as flushers or non-flushers in response to alcohol. RESULTS: In flushers, moderate and heavy alcohol consumption patterns increased the risk of incident hypertension compared with never-drinkers [moderate: HR 1.811 (95% CI 1.084-3.028); heavy: HR 2.494 (95% CI 1.185-5.247)], but non-flushers were not associated with increased risk of incident hypertension according to the alcohol consumption pattern. In addition, a heavy alcohol consumption pattern increased the risk of hypertension among flushers compared with non-flushers [HR 2.232 (95% CI 1.054-4.728)]. CONCLUSION: In this 12-year follow-up study, we observed that moderate and heavy alcohol consumption was associated with an increased risk of hypertension in flushers. Especially, a heavy alcohol consumption pattern in flushers markedly increased the risk of hypertension.
Assuntos
Consumo de Bebidas Alcoólicas , Rubor/induzido quimicamente , Hipertensão , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Coortes , Seguimentos , Humanos , Hipertensão/epidemiologia , Incidência , República da Coreia , Fatores de RiscoRESUMO
Higher motivation could support to lead behavioral change for obese children and adolescents. This study aimed to evaluate the effects of a nutrition care process (NCP)-based intervention targeted on diet and weight status in moderate to severe obese children and adolescents in Korea. One hundred four subjects (mean age: 10.95 years, body mass index (BMI) ≥97th percentile of age-sex) participated in the present study. Subjects were divided into a usual care group (UG) and a nutrition group (NG). All participants underwent nutrition education 6 times. The NG received individual access and continuous monitoring and setting goals with respect to nutritional problems. Consumption of high-calorie, low-nutrient (HCLN) food was significantly decreased (P < .05) and the Diet Quality Index-International (DQI-I) score also increased with respect to sodium (P < .001). The total self-efficacy score was increased from 9.15 to 10.14 points (P < .01). After 24 weeks, the BMI-z-score decreased from 2.27 to 2.19 in the NG (P < .05); however, no group difference was found. BMI-z-score was negatively associated with self-efficacy (ß = -0.03, P < .019). NCP-based intervention might be helpful to solve dietary problems by enhancing self-efficacy and lower BMI-z-score in moderately to severely obese children and adolescents.
Assuntos
Índice de Massa Corporal , Dieta , Motivação , Terapia Nutricional , Valor Nutritivo , Obesidade Infantil , Adolescente , Criança , Comportamento Alimentar , Feminino , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição , Educação de Pacientes como Assunto , Obesidade Infantil/dietoterapia , Obesidade Infantil/psicologia , Obesidade Infantil/terapia , AutoeficáciaRESUMO
BACKGROUND: Significant dropout rates remain a serious concern in pediatric weight control program, but few studies have identified predictors of dropout. AIMS: The objective of the study is to identify factors associated with dropout from a pediatric lifestyle modification weight control program at different phases. METHODS: Data on overweight and obese participants (n = 242) aged 11-18 years in the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition (ICAAN) study were collected at baseline, 6-months, and 24-months through self-report and a laboratory test. Logistic regression analysis was performed for those who dropped out during the first 6-months, and multivariate generalized estimating equation analysis identified longitudinal factors associated with those who dropped out after 24 months. RESULTS: Lower family functioning (OR = 2.30, 95% CI [1.18-4.46]), exercise group (OR = 0.36, 95% CI [0.15-0.86]), lower initial attendance rate (OR = 6.09, 95% CI [2.94-12.6]), and non-self -referral pathways (OR = 2.35, 95% CI [1.05-5.27]) were significantly associated with 6-month dropouts. For late dropout, lower family functioning (OR = 1.71, 95% CI [1.06-2.77]) and lower initial attendance rates (OR = 2.06, 95% CI [1.12-3.81]) remained significant. CONCLUSION: Family function and initial attendance rate were associated with lower dropout rates. Developing a supportive family environment and focusing on the early-stage factors at the intervention's outset may reduce overall dropout rates in obesity prevention intervention.