Jae Heon Kang

Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans

BACKGROUND Associations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors. METHODS We genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database. RESULTS With a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P=0.025, OR=1.47, 95% CI=1.05-2.06; P=0.023, OR=1.53, 95% CI=1.06-2.22) and adults (P=0.018, OR=1.10, 95% CI=1.02-1.19; P=0.001, OR=1.16, 95% CI=1.06-1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P=0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P=0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found. CONCLUSIONS FTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.

Obesity Alters the Microbial Community Profile in Korean Adolescents

Obesity is an increasing public health concern worldwide. According to the latest Organization for Economic Co-operation and Development (OECD) report (2014), the incidence of child obesity in Korea has exceeded the OECD average. To better understand and control this condition, the present study examined the composition of the gut microbial community in normal and obese adolescents. Fecal samples were collected from 67 obese (body mass index [BMI] ≥ 30 kg/m2, or ≥ 99th BMI percentile) and 67 normal (BMI < 25 kg/m2 or < 85th BMI percentile) Korean adolescents aged 13–16 years and subjected to 16S rRNA gene sequencing. Analysis of bacterial composition according to taxonomic rank (genus, family, and phylum) revealed marked differences in the Bacteroides and Prevotella populations in normal and obese samples (p < 0.005) at the genus and family levels; however, there was no difference in the Firmicutes-to-Bacteroidetes (F/B) ratio between normal and obese adolescents samples at the phylum level (F/B normal = 0.50 ± 0.53; F/B obese = 0.56 ± 0.86; p = 0.384). Statistical analysis revealed a significant association between the compositions of several bacterial taxa and child obesity. Among these, Bacteroides and Prevotella showed the most significant association with BMI (p < 0.0001 and 0.0001, respectively). We also found that the composition of Bacteroides was negatively associated with triglycerides (TG), total cholesterol, and high-sensitive C-reactive protein (hs-crp) (p = 0.0049, 0.0023, and 0.0038, respectively) levels, whereas that of Prevotella was positively associated with TG and hs-crp levels (p = 0.0394 and 0.0150, respectively). We then applied the association rule mining algorithm to generate “rules” to identify the association between the populations of multiple bacterial taxa and obesity; these rules were able to discriminate obese from normal states. Therefore, the present study describes a systemic approach to identify the association between bacterial populations in the gut and childhood obesity.

Serum Leptin as a Predictor of Fatty Liver in 7-Year-Old Korean Children

Aim: This study investigated the usefulness of serum leptin as a predictor of fatty liver disease in Korean children. Methods: One hundred and twenty-four children were recruited from urban areas in Korea. Anthropometrical parameters and clinical variables, such as the levels of serum lipids, insulin and leptin, were measured. Fatty liver disease was detected via hepatic sonogram. We also collected dietary intake data using a 24-hour dietary recall for 3 days. Overweight children were identified using the standards established by the International Obesity Task Force. Results: The prevalence of fatty liver disease was 12.1% among all children and was significantly higher in overweight than in normal children (22.5 vs. 7.1%, respectively; p < 0.05). Within normal weight children, children with fatty livers showed a 2-fold increase in serum leptin levels compared with children with healthy livers (6.2 vs. 2.9 ng/ml, respectively; p < 0.05). Within overweight children, elevated serum leptin levels were observed in children with fatty livers. Multiple logistic regression analysis revealed that serum leptin was strongly associated with fatty liver disease, independent of the body mass index. Energy and fat intake, the frequency of fruit and vegetable consumption, and the frequency of physical activity did not differ among children with or without fatty livers. Conclusion: Elevated serum leptin may be a useful parameter when screening for early fatty liver disease among children.

Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents

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 12-15years. 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 19.4kg/m2 in normal-weight adolescents and 31.4kg/m2 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) ß, 0.23; p<0.0001], LDL-C (Std ß, 0.14; p=0.0005) and fasting glucose (Std ß, 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<4×10-4 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.

Relationship between Serum Levels of Body Iron Parameters and Insulin Resistance and Metabolic Syndrome in Korean Children

Objectives An increase in serum ferritin and levels of the cleaved soluble form of transferrin receptor (sTfR) are related to several metabolic conditions. We evaluated the relationship between body iron status indicators, including ferritin and sTfR, and insulin resistance and metabolic syndrome (MetS) in Korean children. Methods A cross-sectional study was conducted on 1350 children in Korea. Anthropometrical parameters; lipid profiles; levels of glucose, insulin, and leptin; and iron status indicators, including sTfR, serum ferritin, serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TS), were analyzed. Results Although serum sTfR levels were significantly higher in boys than in girls (2.20 vs. 2.06 mg/L, p < 0.0001), serum iron and TS were higher in girls than in boys (101.38 vs. 95.77 mg/L, p = 0.027 and 30.15 vs. 28.91%, p = 0.04, respectively). Waist circumference (WC) and leptin were most significantly associated with body iron indicators when adjusted for age and sex. After adjusting for age, sex, and WC, sTfR levels showed the strongest positive association with leptin levels (p = 0.0001). Children in the highest tertile for homeostasis model assessment-insulin resistance (HOMA-IR) had higher TIBC (p = 0.0005) and lower serum iron (p = 0.0341), and the lowest TS (p < 0.0001) after adjustment for confounders. Children with higher sTfR were most significantly associated with risk of MetS compared with those lower sTfR (p = 0.0077). Conclusion The associations of serum levels of iron metabolism markers with leptin levels, HOMA-IR, and MetS suggest that iron-related factors may involve insulin resistance and MetS.

Genome-wide association study of liver enzymes in korean children.

Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.

Associations between estimated desaturase activity and insulin resistance in korean boys.

Objectives Obesity 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. Methods Anthropometric 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. Results Activities 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. Conclusion In young Korean males, higher D6D activity predicts the future development of IR and associated metabolic disorders including dyslipidemia.

The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children.

BACKGROUND 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. METHODS We genotyped 711 children for GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric, biochemical, and dietary measurements. RESULTS 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 or <1), 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 was <1. Additionally, we observed that the GCKR haplotype with a functional variant, rs1260326, influenced lower total and LDL cholesterol in children whose MUFA:SFA ratio was <1. CONCLUSION 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.

A genome-wide association study identifies a LEPR gene as a novel predisposing factor for childhood fasting plasma glucose

• A genome wide association study identifies a LEPR gene as a novel predisposing factor for childhood fasting plasma glucose

Correction: Obesity Alters the Microbial Community Profile in Korean Adolescents.

The fourth author’s name is spelled incorrectly. The correct name is: Min-Kyu Choi. The correct citation is: Hu H-J, Park S-G, Jang HB, Choi M-K, Park K-H, Kang JH, et al. (2015) Obesity Alters the Microbial Community Profile in Korean Adolescents. PLoS ONE 10(7): e0134333. doi:10.1371/journal.pone.0134333 There is an error in affiliation 4 for author Min-Kyu Choi. Affiliation 4 should be: Department of Family Medicine, Kangnam Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea