Increased glutamate in type 2 diabetes in the Korean population is associated with increased plasminogen levels.

BACKGROUND: Glutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated with type 2 diabetes onset, is induced in the liver. METHODS: An analysis of Korean community-based Ansan-Ansung cohort study data as well as functional research using in vitro and mouse models were performed. RESULTS: Groups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose-related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK-Hep-1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome-wide association studies. Among glutamate-related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate-induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor-1 (PAI-1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI-1. CONCLUSIONS: Increased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes.

Identification of Biomarkers Related to Metabolically Unhealthy Obesity in Korean Obese Adolescents: A Cross-Sectional Study.

BACKGROUND: The current study aimed to screen for relationships and different potential metabolic biomarkers involved between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in adolescents. METHODS: The study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences between the MHO and MUO groups. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS. RESULTS: There were significant differences in the three acylcarnitines, five amino acids, glutamine/glutamate ratio, three biogenic amines, two glycerophospholipids, and the triglyceride-glucose index between the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO. Additionally, several metabolites were inversely correlated with MHO in the MUO group. CONCLUSIONS: In this study, the biomarkers found in this study have the potential to reflect the clinical outcomes of the MUO group. These biomarkers will lead to a better understanding of MetS in obese adolescents.

The potential effects of HECTD4 variants on fasting glucose and triglyceride levels in relation to prevalence of type 2 diabetes based on alcohol intake.

Excessive alcohol intake is an important cause of major public health problem in East Asian countries. Growing evidence suggests that genetic factors are associated with alcohol consumption and the risk for alcohol-associated disease, and these factors contribute to the risk of developing chronic diseases, including diabetes. This study aims to investigate the association of type 2 diabetes with genetic polymorphisms within HECTD4 based on alcohol exposure. We performed a genome-wide association study involving the cohorts of the KoGES-HEXA study (n = 50,028) and Ansan and Ansung study (n = 7,980), both of which are prospective cohort studies in Korea. The top three single-nucleotide polymorphisms (SNPs) of the HECTD4 gene, specifically rs77768175, rs2074356 and rs11066280, were found to be significantly associated with alcohol consumption. We found that individuals carrying the variant allele in these SNPs had lower fasting blood glucose, triglyceride, and GGT levels than those with the wild-type allele. Multiple logistic regression showed that statistically significant associations of HECTD4 gene polymorphisms with an increased risk of type 2 diabetes were found in drinkers. Namely, these SNPs were associated with decreased odds of diabetes in the presence of alcohol consumption. As a result of examining the effect of alcohol on the expression of the HECTD4 gene, ethanol increased the expression of HECTD4 in cells, but the level was decreased by NAC treatment. Similar results were obtained from liver samples of mice treated with alcohol. Moreover, a loss of HECTD4 resulted in reduced levels of CYP2E1 and lipogenic gene expression in ethanol-treated cells, while the level of ALDH2 expression increased, indicating a reduction in ethanol-induced hepatotoxicity.

Association of 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene polymorphism with obesity and lipid metabolism in children and adolescents with autism spectrum disorder.

The prevalence of obesity among children and adolescents with autism spectrum disorder (ASD) is higher than that among typically developing children and adolescents. However, very few studies have explored the genetic factors associated with obesity in children and adolescents with ASD. Thus, the aim of this study was to examine the associations between 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene polymorphisms and obesity among children and adolescents with ASD. The study participants consisted of 33 children and adolescents with ASD and 271 age- and sex-matched typically developing controls. We compared the metabolic traits (body mass index, blood pressure, triglyceride, high-density lipoprotein, and fasting glucose levels) between the ASD and control group. Furthermore, we assessed the genotypes of rs12654264 in the HMGCR gene within the participants with ASD, and compared metabolic traits among the different allele subgroups. The mean body mass index (BMI) and triglyceride level of the ASD group were significantly higher than those of the control group. Within the ASD group, the triglyceride level of participants with rs12654264-T alleles was significantly higher than that of participants with A-alleles. A pattern of increasing values in the BMI and fasting glucose was also observed in participants with T allele. This is the first study to show that obesity in children and adolescents with ASD is associated with the cholesterol synthesis pathway. Future studies are needed to further clarify the molecular mechanisms by which the HMGCR gene influences metabolic traits.

Association of Dietary Patterns with Weight Status and Metabolic Risk Factors among Children and Adolescents.

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.

Effects of circuit training or a nutritional intervention on body mass index and other cardiometabolic outcomes in children and adolescents with overweight or obesity.

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.

Metabolomic Signatures for the Effects of Weight Loss Interventions on Severe Obesity in Children and Adolescents.

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.

Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea.

We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4-10 days after symptom onset.

A 24-week intervention based on nutrition care process improves diet quality, body mass index, and motivation in children and adolescents with obesity.

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.

Neuron type-specific expression of a mutant KRAS impairs hippocampal-dependent learning and memory.

KRAS mutations are associated with rare cases of neurodevelopmental disorders that can cause intellectual disabilities. Previous studies showed that mice expressing a mutant KRAS have impaired the development and function of GABAergic inhibitory neurons, which may contribute to behavioural deficits in the mutant mice. However, the underlying cellular mechanisms and the role of excitatory neurons in these behavioural deficits in adults are not fully understood. Herein, we report that neuron type-specific expression of a constitutively active mutant KRASG12V in either excitatory or inhibitory neurons resulted in spatial memory deficits in adult mice. In inhibitory neurons, KRASG12V induced ERK activation and enhanced GABAergic synaptic transmission. Expressing KRASG12V in inhibitory neurons also impaired long-term potentiation in the hippocampal Shaffer-collateral pathway, which could be rescued by picrotoxin treatment. In contrast, KRASG12V induced ERK activation and neuronal cell death in excitatory neurons, which might have contributed to the severe behavioural deficits. Our results showed that both excitatory and inhibitory neurons are involved in mutant KRAS-associated learning deficits in adults via distinct cellular mechanisms.

Amino Acid Metabolites Associated with Chronic Kidney Disease: An Eight-Year Follow-Up Korean Epidemiology Study.

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.

Association between the incidence of hypertension and alcohol consumption pattern and the alcohol flushing response: A 12-year follow-up study.

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.

Evidence-based customized nutritional intervention improves body composition and nutritional factors for highly-adherent children and adolescents with moderate to severe obesity.

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.

Film-thickness-driven superconductor to insulator transition in cuprate superconductors.

The superconductor-insulator transition induced by film thickness control is investigated for the optimally doped cuprate superconductor La1.85Sr0.15CuO4. Epitaxial thin films are grown on an almost exactly matched substrate LaAlO3 (001). Despite the wide thickness range of 6 nm to 300 nm, all films are grown coherently without significant relaxation of the misfit strain. Electronic transport measurement exhibits systematic suppression of the superconducting phase by reducing the film thickness, thereby inducing a superconductor-insulator transition at a critical thickness of ~10 nm. The emergence of a resistance peak preceding the superconducting transition is discussed based on the weak localization. X-ray photoelectron spectroscopy results show the possibility that oxygen vacancies are present near the interface.

Chronic heavy alcohol consumption influences the association between genetic variants of GCK or INSR and the development of diabetes in men: A 12-year follow-up study.

Chronic heavy alcohol consumption is a risk factor for diabetes, which is characterized by impaired ß-cell function and insulin resistance. We aimed to determine whether the longitudinal associations between genetic variants of glucokinase (GCK) and insulin receptor (INSR) and the risk of developing diabetes were influenced by chronic heavy alcohol consumption. Data were obtained from the Korean Genome and Epidemiology Study. To identify candidate variants, 1,520 subjects (726 non-drinkers and 794 heavy drinkers) were included in the baseline cross-sectional study. After excluding patients with diabetes at baseline and those with insufficient data on diabetes incidence, prospective analyses were conducted in 773 subjects (353 non-drinkers and 420 heavy drinkers). In the baseline cross-sectional study, one SNP (rs758989) in GCK and four SNPs (rs7245757, rs1035942, rs1035940, and rs2042901) in INSR were selected as candidate SNPs that interact with alcohol to affect prediabetes and diabetes. We identified that these GCK and INSR polymorphisms are affected by chronic heavy alcohol consumption and have an effect on the incidence of diabetes. The incidence of diabetes was increased in chronic heavy alcohol drinkers carrying the C allele of GCK compared with never-drinkers with the C allele (HR, 2.15; 95% CI 1.30-3.57), and was increased in chronic heavy alcohol drinkers who were not carrying the INSR haplotype (-/-) compared with never-drinkers carrying the AACT haplotype (HR, 1.98; 95% CI 1.24-3.18). Moreover, we observed that the aggravating effects on the late insulin secretion (I/G120 and I/G AUC 60-120) in individuals who were chronic heavy drinkers with C allele of GCK. In the INSR haplotype, chronic heavy drinkers not carrying AACT were associated with lower disposition index. These results potentially suggest that chronic heavy alcohol consumption induce ß-cell dysfunction partially mediated by decreased GCK expression or decline of insulin sensitivity via inhibition of INSR, thereby contributing to the development of diabetes.

2-Aminoadipic acid (2-AAA) as a potential biomarker for insulin resistance in childhood obesity.

Insulin resistance is an important clinical feature of metabolic syndrome, which includes obesity and type 2 diabetes. Increased adipose energy storage in obesity promote insulin resistance and other metabolic adverse effects. To identify a new link between adipocyte and insulin resistance, we performed targeted metabolite profiling of differentiated adipocytes and studied the association between adipogenic metabolites and insulin resistance. We found a correlation between 2-aminoadipic acid (2-AAA) and adipogenic differentiation. Also, circulatory 2-AAA was positively associated with obesity-related factors (fat mass, fat percent, waist circumference, BMI, BMI z-score, triglycerides, insulin, and HOMA-IR) at baseline and after 2 years in the children cohort study. Of these factors, increased BMI z-score and HOMA-IR were the primary independent factors associated with higher 2-AAA levels, and the baseline 2-AAA level was an indicator of the BMI z-score after 2 years. To validate the relationship between 2-AAA and obesity-related factors, we analyzed changes in 2-AAA levels following obesity intervention programs in two independent studies. In both studies, changes in 2-AAA levels during the intervention period were positively correlated with changes in the BMI z-score and HOMA-IR after adjusting for confounders. Moreover, the 2-AAA levels were increased in cell and mouse models of obesity-related insulin resistance. Excess 2-AAA levels led to impaired insulin signaling in insulin-sensitive cells (liver, skeletal muscle and adipose cells) and caused abnormal gluconeogenesis. Our results demonstrate that 2-AAA is associated with adipogenesis and insulin resistance. In this regard, 2-AAA could be a potential biomarker of obesity and obesity-related metabolic disorders.

Evidence-based Nutritional Intervention Protocol for Korean Moderate-Severe Obese Children and Adolescents.

Diet-related behavioral modification for healthy eating and lifestyle is required to improve childhood obesity. The present study aimed to develop customized nutritional intervention protocol and education program to find barriers to adhere healthy diet and lifestyle for moderate to severe obese children and adolescents and their families. Theoretical framework approaches can be used to change behavior and achieve goals. Previous studies that described the relationship between behavioral modification and nutrition education theory were reviewed. The social cognitive theory and transtheoretical model were employed with behavioral changes to target a healthful diet and lifestyle. The nutrition care process (NCP) model was adopted to customize nutrition care for the participants. Customized nutritional intervention protocol was developed following as the four steps of the NCP. Firstly, nutrition status of the participants was assessed by the nutrition expert. Nutrition problems were described as "inadequate energy intake," "overweight/obesity," or "food and nutrition-related knowledge deficit." All nutrition sessions were designed for nutrition intervention to give nutritional knowledge and a practical mission in real life for individual goal setting and self-control. Meal planning, portion control, healthy snack selection and cooking with fruits and vegetables were consisted of five components of the nutrition education session. During each session, the participants and their families were interviewed by a nutrition expert for monitoring and evaluating diet-related goal setting and achievement. A theoretical and evidence-based nutritional intervention was developed for the secondary to tertiary prevention of childhood obesity. This nutrition intervention protocol and program might be helpful for the further research on childhood obesity. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002111.

Protective Effects of Dietary MUFAs Mediating Metabolites against Hypertension Risk in the Korean Genome and Epidemiology Study.

BACKGROUND AND AIMS: Metabolites related to dietary factors can be used to identify biological markers to prevent metabolic disease. However, most studies have been conducted in the United States and Europe, and those in the Asian region are limited. We investigated the effects of dietary monounsaturated fatty acids (MUFAs) and metabolites on new-onset hypertension in the Korean Genome and Epidemiology Study. METHOD AND RESULTS: A total of 1529 subjects without hypertension were divided into tertiles of dietary MUFAs intake. After a 4-year follow-up, 135 serum metabolites were measured using the AbsoluteIDQ p180 kit. During the 4-year follow-up period, 193 new-onset hypertension incidences were observed. The highest MUFAs intake group was inversely associated with the risk of hypertension compared with the lowest MUFAs intake group (odds ratio (OR) = 0.49, (95% confidence interval (CI) = 0.29-0.82)). Of the 135 metabolites, eight were significantly associated with MUFAs intake. Phosphatidylcholine-diacyl (PC aa) C 38:1 and hydroxysphingomyelin (SM OH) C 16:1 were associated with a decrease in hypertension risk (PC aa C 38:1, OR = 0.60 (95% CI = 0.37-0.96); SM OH C 16:1, OR = 0.42 (95% CI = 0.20-0.90)). The highest MUFAs intake group had a significantly decreased risk of hypertension, even considering PC aa C 38:1 and SM (OH) C 16:1 as a mediator. CONCLUSION: We confirmed that dietary MUFAs intake, and PC aa C 38:1 and SM (OH) C 16:1 had protective effects against hypertension. Furthermore, high MUFAs intake combined with PC aa C 38:1 and SM (OH) C 16:1 has the most significant effect on reducing the risk hypertension.

The association between alcohol metabolism and genetic variants of ADH1A, SRPRB, and PGM1 in Korea.

BACKGROUND: Excessive alcohol consumption is a major public health problem in East Asian countries. Alcohol use leads to a cascade of problems including increased chances of risky behavior and a wide range of negative health consequences, from alcoholic liver disease to upper gastric and liver cancer. These alcohol effects are known to be influenced by ethnic variability and genetics. METHODS: In this study, subjects were administered a single dose of alcohol (0.6 g/kg for men or 0.4 g/kg for women), and blood alcohol and acetaldehyde concentrations were measured eight times over 5 hours. To investigate genetically susceptible factors to alcohol metabolism, we selected single-nucleotide polymorphisms (SNP) of genes identified by prior genetic association studies for alcohol metabolism, alcohol consumption, alcohol dependence, and related traits, and performed genotyping on all subjects (n = 104). RESULTS: We identified variations in the ADH1A, SRPRB, and PGM1 genes, which are directly associated with blood alcohol or acetaldehyde concentrations. Namely, the T allele of SRPRB rs17376019 and the C allele of PGM1 rs4643 were associated with lower blood alcohol levels, while the ADH1 rs1229976 C allele group exhibited markedly higher blood acetaldehyde levels than those of the ADH1 rs1229976 T allele group. CONCLUSION: This study demonstrates that genetic variations in ADH1A, SRPRB, and PGM1 are associated with variations in blood alcohol and acetaldehyde concentration after alcohol intake.

The Effect of a Multidisciplinary Lifestyle Intervention on Obesity Status, Body Composition, Physical Fitness, and Cardiometabolic Risk Markers in Children and Adolescents with Obesity.

This study aimed to develop a multidisciplinary lifestyle intervention program targeted at children and adolescents with moderate to severe obesity, and assess the additional effects of exercise intervention when compared to usual care. Overall, the 103 enrolled participants were ≥85th percentile of age and sex-specific body mass index (BMI). Participants were divided into groups that received 16 weeks of either usual care or exercise intervention. The BMI z-score of the overall completers decreased by about 0.05 after the 16-week intervention (p = 0.02). After the intervention, only the exercise group had a significantly lower BMI z-score than the baseline score by about 0.1 (p = 0.03), but no significant group by time interaction effects were observed. At the 16-week follow-up, significant group by time interaction effects were observed in percentage body fat (%BF) (ß = -1.52, 95%CI = -2.58⁻-0.45), lean body mass (LM) (ß = 1.20, 95%CI = 0.12⁻2.29), diastolic blood pressure (ß = -5.24, 95%CI = -9.66⁻-0.83), high-sensitivity C-reactive protein (ß = -1.67, 95%CI = -2.77⁻-1.01), and wall sit test score (ß = 50.74, 95%CI = 32.30⁻69.18). We developed a moderate-intensity intervention program that can be sustained in the real-world setting and is practically applicable to both moderate and severe obesity. After interventions, the exercise group had lower %BF and cardiometabolic risk markers, and higher LM and leg muscle strength compared to the usual care group.