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Chronic alcohol consumption is known to be associated with type 2 diabetes (T2D), which is developed by two underlying mechanisms, β-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 β-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 β-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 β-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.

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.

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.

Chronic heavy alcohol consumption is a risk factor for diabetes, which is characterized by impaired β-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 β-cell dysfunction partially mediated by decreased GCK expression or decline of insulin sensitivity via inhibition of INSR, thereby contributing to the development of diabetes.

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.

Background and aims Alcohol consumption is generally associated with increased risk of hypertension. However, the effect of alcohol intake on the incidence of hypertension remains controversial due to inconsistent results across studies. We investigated the association between alcohol intake and hypertension in a Korean population. Methods and results The two studies that we evaluated herein, the CAVAS study (N = 6259) and the Ansan-Ansung study (N = 2461), were part of the Korean Genome and Epidemiology study on participants aged between 40 and 69 years who underwent community-based health checkups (2 years for the CAVAS study follow-up and 12 years for the Ansan-Ansung study follow-up). We categorized the participants into four groups based on baseline and follow-up period measurements. We found that baseline alcohol consumption increased the risk of incident hypertension in the CAVAS study [HR (95% CI), low: 1.094 (0.848–1.411); intermediate: 1.661 (1.227–2.141); high: 1.723 (1.274–2.330)]. Intermediate and high alcohol consumption were associated with increased risk of incident hypertension in men [2.086 (1.438–3.027) for intermediate, and 1.952 (1.294–2.944) for high], but only women had increased risk of incident hypertension with high consumption [1.950 (1.100–3.455)]. In addition, we found a positive association between the alcohol consumption pattern (over 10 years) and the risk of incident hypertension in the Ansan-Ansung study [HR (95% CI), light: 1.316 (1.126–1.539); moderate: 1.445 (1.193–1.750); heavy: 1.897 (1.488–2.419)]. Moderate and heavy consumption patterns carried higher risks of incident hypertension compared with never-drinking in men [moderate: 1.292 (1.033–1.617); heavy: 1.703 (1.293–2.242)], but women with light consumption patterns were at increased risk of incident hypertension [1.572 (1.302–1.899)]. Conclusions This large prospective cohort study revealed a linear association between baseline alcohol consumption, subsequent alcohol consumption patterns (over more than 10 years), and hypertension risk in the Korean population.

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) (β = 1.55), insulin level (β = 1.25), and body mass index (BMI) (β = 0.53) and it was positively associated with HOMA-IR ≥ 2.6 (OR = 2.11, 95% CI: 1.227–3.638) (p &lt, 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 &lt, 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.

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 (β, -0.11; 95% confidence interval (CI), -0.20 to -0.023) and adiponectin (β, 1.31; 95% CI, 1.08 to 1.58); and between nutritional versus usual care group in waist circumference (β, -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.

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 β cell functions are examined.Iron overload is induced in INS-1 rat insulinoma pancreatic β cells and it is found that iron overload dramatically reduce expression of the vitamin D receptor (VDR). Iron overload-induced β cell dysfunction is rescued by 1,25-dihydroxyvitamin DThe authors show that functional failure of β cells due to iron accumulation is rescued by 1,25(OH)

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.

BACKGROUND This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS In total, 168 participants (89 boys and 79 girls) aged 10-16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P

ObjectiveThe early identification of predictors related to cardiovascular disease risk factor clustering (CVD-RFC) can help prevent chronic disease. We aimed to identify the risk factors for CVD-RFC in adolescents.MethodsA prospective longitudinal cohort study design was used to obtain data included in these analyses from school-aged children who participated in the Korean Child-Adolescent Study 2008–2014. A total of 1309 children aged 6–15 years were enrolled. We compared the participants based on the presence or absence of CVD-RFC and examined the cumulative incidence of CVD-RFC.ResultsOf the total 1309 children, 410 (31.32%) had CVD-RFC in adolescence. A higher average household income ≥3 million Korean Republic won (KRW)/month (3–5 million KRW/month: HR 0.75 (95% CI 0.58 to 0.97); ≥5 million KRW/month: HR 0.58 (95% CI 0.44 to 0.77)) was associated with a lower CVD-RFC incidence, while the presence of parental CVD history (HR 1.28 (95% CI 1.04 to 1.57)), overweight or obesity (HR 3.83 (95% CI 3.05 to 4.80)) and shorter sleep duration of 8–9 hour/day (HR 1.80 (95% CI 1.05 to 3.07)) and ConclusionsObesity in childhood, short sleep duration and parental factors such as low socioeconomic status and parental history of CVD are significant risk factors for the development of CVD-RFC in adolescents. Efforts to create awareness regarding sufficient sleep duration in children via intervention programmes targeting cardiometabolic health in children and special attention to lifestyle modifications and socioeconomic components of the family should be considered.

To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA). However, ADMA showed a higher association with adolescent obesity (P

Context Irisin, a novel exercise-induced myokine, has been suggested to regulate energy metabolism. Objective We studied the relationship between circulating irisin and metabolic and metabolite profiles of Korean adolescents, and investigated the effects of physical activity, obesity, and metabolic syndrome (MetS) on irisin levels. Materials and Methods Data were obtained from the Korean Children–Adolescents Study. Our cross-sectional study included 618 adolescents (370 normal-weight and 248 obese adolescents; 316 boys and 302 girls) aged 12–15 years. Body composition was determined using an impedance body composition analyzer and general participant characteristics and lifestyle information were obtained from questionnaires. Serum irisin levels were measured using a commercial kit. Results Mean body mass index (BMI) was 19.4 kg/m 2 in normal-weight adolescents and 31.4 kg/m 2 in obese adolescents. Circulating irisin was positively correlated with adiposity indices, including BMI z-score, waist circumference, percent body fat, fat mass, fat-free mass, fat mass to fat-free mass ratio, and lipid and glucose metabolism markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, and homeostasis model assessment-estimated insulin resistance (all p ≤ 0.006). Of these, increased body fat mass [standardized (Std) s, 0.23; p p = 0.0005) and fasting glucose (Std s, 0.08; p = 0.0383) were the main independent factors associated with higher irisin levels. Moreover, elevated serum irisin was associated with the risk of obesity [odds ratio (OR], 2.2; confidence interval (CI), 1.19–3.87] and MetS (OR, 2.0; CI, 1.15–3.47). Furthermore, irisin and branched-chain amino acids were positively associated ( p − 4 for Bonferroni correction). Additionally, in the normal-weight group, girls had higher irisin levels than boys ( p = 0.006) and adolescents who engaged in regular physical activity had higher levels of irisin than sedentary adolescents ( p = 0.0388). The relationship between physical activity and irisin levels was not observed in obese adolescents. Conclusions Elevated serum irisin was independently associated with the risk of obesity and positively correlated with unhealthy metabolic parameters and metabolites. Moreover, irisin levels were higher in active versus sedentary adolescents in the normal-weight group, but not in the obese group. Our findings suggest that irisin plays an important role in metabolic disorders and may be affected by physiopathological status.

// Suman Lee 1 , Hyo Jin Kim 2 , Sohee Han 1 , Jae-Pil Jeon 1 , Sang-Ick Park 2 , Ho-Yeong Yu 1 , Mi Yeong Hwang 1 and Juyoung Lee 1 1 Center for Genome Science, National Institute of Health, Chungju, Chungcheongbuk-do, 361-951, Republic of Korea 2 Center for Biomedical Sciences, National Institute of Health, Chungju, Chungcheongbuk-do, 361-951, Republic of Korea Correspondence to: Suman Lee, email: smnl93@gmail.com Keywords: cg16672562, HIF3A , obesity, CpG methylation, cis-meQTL Received: January 16, 2017 Accepted: May 27, 2017 Published: June 27, 2017 ABSTRACT Differential methylations of the HIF3A (hypoxia-inducible factor 3a) gene have been linked to body mass index (BMI). To explore the association of these methylations to childhood obesity, we measured 5 CpG methylation sites (cg27146050, cg46801562, cg22891070, cg16672562 and cg46801675) in intron 1 of the HIF3A gene by pyrosequencing, in the Korean population (mean age: 13.9 yrs, 305 obese cases and 387 controls). Two CpG methylations, cg46801562 and cg16672562, had statistically significant association with childhood obesity ( P = 2.09E-9 and 1.66E-7, respectively). Notably, in the case of cg16672562, all correlations were significantly positive with BMI ( beta = 0.285, P = 1.652E-13), waist-hip ratio ( beta = 0.0028, P = 1.42E-15) and fasting plasma glucose level ( beta = 0.0645, P = 2.61E-4), when analyzed by linear regression, with age and sex as covariates. We investigated any genetic effect of cg16672562 methylation by using 14 single nucleotide polymorphisms (SNP) identified by exome sequencing of the HIF3A locus . cg16672562 methylation showed no statistically significant changes due to the 14 polymorphisms. In this study, we show that cg16672562 is the most significant blood DNA methylation marker for childhood obesity in the Korean population, and might be independent of any underlying HIF3A genetic background.

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 (β = -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.

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.

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 &ge, 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) (&beta, = &minus, 1.52, 95%CI = &minus, 2.58&ndash, &minus, 0.45), lean body mass (LM) (&beta, = 1.20, 95%CI = 0.12&ndash, 2.29), diastolic blood pressure (&beta, 5.24, 95%CI = &minus, 9.66&ndash, 0.83), high-sensitivity C-reactive protein (&beta, 1.67, 95%CI = &minus, 2.77&ndash, 1.01), and wall sit test score (&beta, = 50.74, 95%CI = 32.30&ndash, 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.

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, we examined the effects of iron and vitamin D on pancreatic s cell functions. METHODS AND RESULTS: We induced iron overload in INS-1 rat insulinoma pancreatic s cells and found that iron overload dramatically reduced expression of the vitamin D receptor (VDR). Iron overload-induced s cell dysfunction was rescued by 1,25(OH)2 D3 cotreatment via restoration of VDR level and the consequent maintenance of Ca2+ homeostasis. We also observed iron accumulation in the islets of 22-month-old C57BL/6 mice fed a chow diet (1000 IU vitamin D3 /kg). In contrast, islet iron accumulation and hyperinsulinemia were ameliorated in mice fed a vitamin D3 -supplemented diet (20,000 IU/kg). CONCLUSIONS: We showed that functional failure of s cells due to iron accumulation was rescued by 1,25(OH)2 D3 , and iron overload significantly reduced VDR levels in s cells. These results suggest that iron and vitamin D inversely influence pancreatic s cell function. This article is protected by copyright. All rights reserved.

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.

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.

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 [β]: -1.39, 95% confidence interval [CI]: -1.81 to -0.97; β: -0.34, 95%CI: -0.61 to -0.06; β: -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.

Excessive tissue iron levels are a risk factor for insulin resistance and type 2 diabetes, which are associated with alterations in iron metabolism. However, the mechanisms underlying this association are not well understood. This study used human liver SK-HEP-1 cells to examine how excess iron induces mitochondrial dysfunction and how hepcidin controls gluconeogenesis. Excess levels of reactive oxygen species (ROS) and accumulated iron due to iron overload induced mitochondrial dysfunction, leading to a decrease in cellular adenosine triphosphate content and cytochrome c oxidase III expression, with an associated increase in gluconeogenesis. Disturbances in mitochondrial function caused excess iron deposition and unbalanced expression of iron metabolism-related proteins such as hepcidin, ferritin H and ferroportin during the activation of p38 mitogen-activated protein kinase (MAPK) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are responsible for increased phosphoenolpyruvate carboxykinase expression. Desferoxamine and n-acetylcysteine ameliorated these deteriorations by inhibiting p38 MAPK and C/EBPα activity through iron chelation and ROS scavenging activity. Based on experiments using hepcidin shRNA and hepcidin overexpression, the activation of hepcidin affects ROS generation and iron deposition, which disturbs mitochondrial function and causes an imbalance in iron metabolism and increased gluconeogenesis. Repression of hepcidin activity can reverse these changes. Our results demonstrate that iron overload is associated with mitochondrial dysfunction and that together they can cause abnormal hepatic gluconeogenesis. Hepcidin expression may modulate this disorder by regulating ROS generation and iron deposition.

Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome.In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit.We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (p0.05). Obese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome.High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases.

Moderate alcohol consumption is generally associated with reduced risk of type 2 diabetes. However, this beneficial effects of alcohol intake remains controversial due to inconsistent results across studies. The analysis was performed using data from the Ansung-Ansan cohort study. We categorized the participants into four groups—based on the baseline (one-point measure; non-drinking

Some epidemiological studies suggest an inverse correlation between cancer incidence and Alzheimer's disease (AD). In this study, we demonstrated experimental evidences for this inverse relationship. In the co-expression network analysis using the microarray data and GEO profile of gene expression omnibus data analysis, we showed that the expression of peroxiredoxin 6 (PRDX6), a tumor promoting protein was significantly increased in human squamous lung cancer, but decreased in mutant presenilin 2 (PS2) containing AD patient. We also found in animal model that mutant PS2 transgenic mice displayed a reduced incidence of spontaneous and carcinogen-induced lung tumor development compared to wildtype transgenic mice. Agreed with network and GEO profile study, we also revealed that significantly reduced expression of PRDX6 and activity of iPLA2 in these animal models. PS2 mutations increased their interaction with PRDX6, thereby increasing iPLA2 cleavage via increased γ-secretase leading to loss of PRDX6 activity. However, knockdown or inhibition of γ-secretase abolished the inhibitory effect of mutant PSs. Moreover, PS2 mutant skin fibroblasts derived from patients with AD showed diminished iPLA2 activity by the elevated γ-secretase activity. Thus, the present data suggest that PS2 mutations suppress lung tumor development by inhibiting the iPLA2 activity of PRDX6 via a γ-secretase cleavage mechanism and may explain the inverse relationship between cancer and AD incidence.

Alzheimer's disease (AD) is the most common cause of dementia in individuals over 65 years old. However, to date, no useful early diagnostic markers for AD have been discovered. We examined the utility of plasminogen activator inhibitor-1 (PAI-1) as a potential biomarker for AD in subjects with mild cognitive impairment (MCI) or AD, as well as in nondemented healthy controls. Plasma PAI-1 levels were measured by enzyme-linked immunosorbent assays (ELISAs) in samples collected from 76 patients with MCI, 74 patients with AD, and 76 healthy controls. Our results show that plasma PAI-1 levels gradually increased as dementia progressed. The mean levels of plasma PAI-1 in patients with MCI and AD patients were significantly higher than those of in healthy controls. Consistently, neuropsychological examination (e.g., MMSE, CDR) also demonstrated significant correlations between the plasma PAI-1 levels and cognitive function. In conclusion, the level of plasma PAI-1 is a potential biomarker for the early detection and diagnosis of AD.

ObjectivesObesity in childhood increases the risk of obesity in adulthood, and is predictive of the development of metabolic disorders. The fatty acid compositions of various tissues, including blood, are associated with obesity and obesity-associated disorders. Thus, tracking plasma phospholipid (PL) features and metabolic parameters in young individuals may strengthen the utility of fatty acid composition as an early biomarker of future metabolic disorders.MethodsAnthropometric and blood biochemical data were obtained from 131 Korean males aged 10.5 ± 0.4 years, and followed up at 2 years. We analyzed the plasma PL fatty acids according to obesity. Obese children were defined as those with a body mass index (BMI) greater than the 85th percentile for age and gender, based on Korean child growth standards.ResultsActivities of lipid desaturases, stearyl-CoAD (SCD-16,16:1n-7/16:0), delta-6D (D6D, 20:3n-6/18:2n-6), and delta-5D (D5D, 20:4n-6/20:3n-6), were estimated. Obese individuals had significantly higher proportions of palmitoleic acid (16:1n-7) and dihomo-gamma linolenic acid (DGLA, 20:3n-6) at both baseline and follow-up than did lean individuals. The activities of SCD-16 and D6D were higher in obese than lean boys. The baseline SCD-16 activity level was positively associated with the baseline waist circumference (WC) and the metabolic risk score. The baseline D6D level was positively associated with WC and also with the homeostasis model of assessment of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance (IR), and metabolic risk score at both baseline and follow-up.ConclusionIn young Korean males, higher D6D activity predicts the future development of IR and associated metabolic disorders including dyslipidemia.

OBJECTIVES: Evidence-based customized nutritional interventions are required for effective treatment of moderately-severely obese children and adolescents. METHODS: Eligible participants who agreed to participate in the intervention program provided informed consent. Customized nutritional intervention was implemented for each participant based on a nutrition care process (NCP) model. Sociodemographic assessment, anthropometrics, biochemical 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: One hundred three [mean age: 12.4 years, severely obese: n = 69(67%)] children and adolescents were assessed at baseline. After 16 weeks, there were significant improvements in body composition [BMI (−0.8 ± 0.9, P

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

We recently reported that glutamate carboxypeptidase II (GCPII) has a new physiological function degrading amyloid-β (Aβ), 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 Aβ degradation occurs through S1 pocket but not through S1′ pocket responsible for NAAG hydrolysis. Treatment with compound 2 prevented GCPII from Aβ 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 Aβ degradation. Pre-incubation with NAAG and Aβ did not affect Aβ degradation and NAAG hydrolysis, respectively. These data suggest that GCPII has two distinctive binding sites for two different substrates and that Aβ degradation occurs through binding to S1 pocket of GCPII.

This cross-sectional study was performed to examine the association between alcohol consumption and insulin secretion and sensitivity using the Korean Genome and Epidemiology Study. Alcohol consumption levels were categorized into four groups: (i) abstainers, (ii) low (

Obesity is a major risk factor for type 2 diabetes. To unravel the genetic determinants of obesity-associated diabetes, we performed a genome-wide study using the 1,000 Genomes-based imputation in a Korean childhood cohort (KoCAS-1, n = 484) and carried out de novo replication in an independent population (KoCAS-2, n = 1,548). A novel variant (rs10879834) with multiple diverse associations for obesity-related traits was also found to be replicated in an adult cohort (KARE, n = 8,842). Functional annotations using integrative epigenetic analyses identified biological significance and regulatory effects with an inverse methylation-expression correlation (cg27154343 in the 5′-UTR of the KCNC2 gene), tissue-specific enhancer mark (H3K4me1), and pathway enrichment (insulin signaling). Further functional studies in cellular and mouse models demonstrated that KCNC2 is associated with anti-obesogenic effects in the regulation of obesity-induced insulin resistance. KCNC2 shRNA transfection induced endoplasmic reticulum (ER) stress and hepatic gluconeogenesis. Overproduction of KCNC2 decreased ER stress, and treatment with metformin enhanced KCNC2 expression. Taken together, these data suggest that reduction of KCNC2 is associated with modified hepatic gluconeogenesis and increased ER stress on obesity-mediated diabetic risk. An integrative multi-omics analysis might reveal new functional and clinical implications related to the control of energy and metabolic homeostasis in humans.

Background The gut microbiota has emerged as an important environmental factor associated with obesity, type 2 diabetes, and cardiovascular disease, through its interactions with dietary factors. Therefore, we analyzed the composition of the fecal microbiota and levels of biochemical markers related to metabolic disease according to dietary pattern in Korean adolescents. Methods We collected fecal samples from 112 student subjects aged 13–16 years with sufficient information available regarding clinical biomarkers and diet, and performed 16S rRNA targeted gene sequencing. Results Regarding bacterial composition according to taxonomic rank, we found that traditional dietary patterns enriched in plant-based and fermented foods were associated with higher proportions of Bacteroides (Bacteroidaceae) and Bifidobacterium (Bifidobacteriaceae-Actinobacteria) and a lower proportion of Prevotella (Prevotellaceae) relative to modified Western dietary patterns (a greater proportion of animal-based foods). Specifically, the proportion of Bacteroides (Bacteroidaceae) was associated with intake of plant-based nutrients such as fiber; however, that of Prevotella (Prevotellaceae) was negatively associated with these factors. Additionally, we observed that the increase of prevotella (Prevotellaceae) and decrease of Bacteroides (Bacteroidaceae) and Ruminococcaceae had a higher risk of obesity. We also found that the traditional dietary pattern was negatively associated with general and central adiposity and levels of clinical biomarkers, including AST, ALT, total cholesterol, triglyceride, hs-CRP, insulin, and HOMA-IR, whereas the positive associations were found for a modified Western dietary pattern. Conclusions These findings suggest that the gut microbiota composition differs markedly according to dietary intake and suggest a role for diet in promoting a gut microbiome associated with the pathogenesis of metabolic disease. Electronic supplementary material The online version of this article (doi:10.1186/s40795-016-0125-z) contains supplementary material, which is available to authorized users.

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

Despite the fact that many cancer cells are sensitive to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, human K562 leukemic cells showed resistance to TRAIL-induced apoptosis. Interestingly, K562/R3 cells, a stable TRAIL-sensitive variant isolated from K562 cells, showed down-regulation of DNA-PK/Akt pathway and a high responsiveness to TRAIL-mediated growth inhibition and apoptosis. We revealed that siRNA-mediated suppression of DNA-PKcs led to decreased phosphorylation of Akt and Bad, a target molecule of Akt, and increased expression of DR4/DR5. Also, we found that suppression of DNA-PKcs using siRNA down-regulated c-FLIP and sensitized K562 cells to TRAIL-induced apoptosis through activation of caspase-8, -9 and -3. In addition, we revealed that treatment with DMNB, a specific inhibitor of DNA-PK, resulted in an increase of DR4/DR5 mRNA levels and their surface expression and a decrease of c-FLIP mRNA levels in K562 cells. DMNB potentiated TRAIL-induced cytotoxicity and apoptosis through inhibition of DNA-PK/Akt pathway and activation of caspase-8, -9 and -3 in K562 cells. This study is the first to show that a protective role of DNA-PK/Akt pathway against TRAIL-induced apoptosis and thus TRAIL in combination with agents that inhibit DNA-PK/Akt pathway would have clinical applicability in treating TRAIL-insensitive human leukemic cells. This model may provide a novel framework for overcoming TRAIL resistance of other cancer cells with agents that inhibit DNA-PK/Akt pathway.

Taxol (paclitaxel) is a potent anticancer drug that has been found to be effective against several tumor types, including cervical cancer. However, the exact mechanism underlying the antitumor effects of paclitaxel is poorly understood. Here, paclitaxel induced the apoptosis of cervical cancer HeLa cells and correlated with the enhanced activation of caspase-3 and TAp73, which was strongly inhibited by TAp73β small interfering RNA (siRNA). In wild-type activating transcription factor 3 (ATF3)–overexpressed cells, paclitaxel enhanced apoptosis through increased α and β isoform expression of TAp73; however, these events were attenuated in cells containing inactive COOH-terminal–deleted ATF3 [ATF3(ΔC)] or ATF3 siRNA. In contrast, paclitaxel-induced ATF3 expression did not change in TAp73β-overexpressed or TAp73β siRNA–cotransfected cells. Furthermore, paclitaxel-induced ATF3 translocated into the nucleus where TAp73β is expressed, but not in ATF3(ΔC) or TAp73β siRNA–transfected cells. As confirmed by the GST pull-down assay, ATF3 bound to the DNA-binding domain of p73, resulting in the activation of p21 or Bax transcription, a downstream target of p73. Overexpression of ATF3 prolonged the half-life of TAp73β by inhibiting its ubiquitination and thereby enhancing its transactivation and proapoptotic activities. Additionally, ATF3 induced by paclitaxel potentiated the stability of TAp73β, not its transcriptional level. Chromatin immunoprecipitation analyses show that TAp73β and ATF3 are recruited directly to the p21 and Bax promoter. Collectively, these results reveal that overexpression of ATF3 potentiates paclitaxel-induced apoptosis of HeLa cells, at least in part, by enhancing TAp73β's stability and its transcriptional activity. The investigation shows that ATF3 may function as a tumor-inhibiting factor through direct regulatory effects on TAp73β, suggesting a functional link between ATF3 and TAp73β. (Mol Cancer Res 2008;6(7):1232–49)

Activating transcription factor 3 (ATF3) is an early-induced gene involved in diverse cellular functions in response to various stresses including viral infection. Here we observed marked reduction of ATF3 by coxsackievirus B3 (CVB3) infection and investigated the regulation and functional role of ATF3 in HeLa cells for the understanding of biological significance of ATF3 downregulation. CVB3 infection markedly reduced ATF3 expression at mRNA and protein levels in parallel with p53 degradation, and preservation of p53 expression rescued CVB3 infection-induced ATF3 downregulation. ATF3 overexpression stimulated apoptotic cell death following CVB3 infection, accompanying with augmentation of CVB3 infection-induced eIF2alpha phosphorylation. However, ATF3 overexpression did not affect viral protein production but promoted virus progeny release. Taken together, our results suggest that ATF3 is under control of p53 in part and that the ATF3 downregulation via p53 degradation may contribute to effective viral production as a modulation mechanism of CVB3 infection-induced cell death.

Glucokinase regulator (GCKR) plays important roles in the regulation of glucokinase (GK) activity and the metabolism of glucose and lipids. We investigated whether the association between GCKR genetic variants with serum lipids in Korean adults is replicated in children, and whether these genetic influences might be modulated by dietary monounsaturated fatty acid relative to saturated fatty acid (MUFA:SFA) ratio.We genotyped 711 children for GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric, biochemical, and dietary measurements.The major allele carriers of rs780094 and rs780092 in adults had significantly higher serum total cholesterol and triglycerides levels compared to noncarriers. Five variants in children, including rs780094 and rs780092, correlated similarly with high total and low-density lipoprotein (LDL) cholesterol. When the dietary MUFA:SFA ratio was dichotomized (MUFA:SFA≥1 or1), the aggravating effects of the major allele on total cholesterol, LDL cholesterol, and triglycerides were only evident in the group in which MUFA:SFA ratio was1. Additionally, we observed that the GCKR haplotype with a functional variant, rs1260326, influenced lower total and LDL cholesterol in children whose MUFA:SFA ratio was1.We replicated the genetic association effect of GCKR on total cholesterol in children, and found that the interaction effects between GCKR genetic variants and the dietary MUFA:SFA ratio on lipid levels, were commonly observed in Korean adults and children.