Yae Jung Hyun

Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: Low inflammation and LDL oxidation in MHO women

Objective:Recently, a subtype of obesity characterized as a metabolically healthy but obese (MHO) individual has been identified. However, limited data are available on these MHO individuals’ metabolic and inflammatory profiles, and the effect of weight loss on these profiles. We investigated metabolic and inflammatory markers in MHO women to determine the effects of a 12-week weight loss on those markers.Subjects:One hundred and twenty-nine overweight-obese Korean women participated for 12 weeks in a clinical intervention study involving a 300 kcal/day intake reduction. The subjects were divided into two groups: MHO and metabolically abnormal obese (MAO) individuals.Methods:Computed tomography was performed. C-reactive protein (CRP), interkeukin-6 (IL-6) and oxidized low-density lipoprotein (LDL), as well as blood lipids, glucose and insulin concentrations were determined at baseline and after weight loss.Results:At baseline, plasma CRP (P<0.001), IL-6 (P<0.05) and oxidized LDL (P<0.001) levels were significantly lower in the MHO group than in the MAO group. Visceral fat at L1 (P<0.005) and visceral fat at L4 (P<0.001) were significantly lower in the MHO group than in the MAO group. The treatment induced weight loss averaging 3.11% of initial body weight, and the degree of weight loss between the two groups was similar. Visceral fat at L1 and L4 was reduced from its initial values by 3.2 and 5.4%, respectively, after weight loss. The levels of CRP (P<0.05) and oxidized LDL (P<0.01) were significantly reduced in the MAO group after the 12-week weight loss, whereas these effects were not seen in the MHO group.Conclusions:Our results showed that MHO individuals exhibited lower visceral fat accumulation and more favorable metabolic and inflammatory states than MAO individuals. After a 12-week weight loss program, significant reductions in blood lipids, CRP and oxidized LDL levels were observed in MAO individuals. However, there was no measurable effect of weight loss on lipid profiles and inflammation in MHO individuals, indicating differing effects of weight loss on these markers between MAO and MHO groups.

The apolipoprotein A5 -1131T > C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease.

BACKGROUND The association between -1131T>C single nucleotide polymorphism (SNP) of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the possibility that this SNP could be related to coronary artery disease (CAD) risk. Therefore, we investigated the association of this APOA5 -1131T>C SNP with circulating concentrations of APOA5, triglyceride and CAD in Koreans. METHODS CAD patients (n=741) and age-, sex-matched healthy controls (n=741) were genotyped for the APOA5 -1131T>C SNP. The main outcome measures were the odds ratio (OR) on CAD risk and lipid variables, APOA5 concentration and LDL particle size. RESULTS The presence of the minor allele at the -1131T>C SNP was associated with an increased risk of CAD [OR 1.34 (95% CI, 1.09-1.65), P=0.007] after adjusting for BMI, alcohol consumption, systolic blood pressure and diastolic blood pressure. There was an association between the APOA5 concentration and the -1131T>C genotype in controls (T/T: 245+/-7 ng/ml, T/C: 220+/-6, C/C: 195+/-12; P=0.001) and CAD patients (T/T: 218+/-8 ng/ml, T/C: 185+/-7, C/C: 169+/-12; P<0.001). Subjects with T/C or C/C in control and CAD patient groups showed higher triglyceride than those with T/T genotype. Also, the -1131T>C polymorphism was associated with LDL particle size (P=0.003), with the T/C or C/C controls having smaller size than the T/T controls. CONCLUSIONS The APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. This is consistent with the observed association between the -1131C SNP, increased triglycerides as well as small LDL particle size.

Atherogenecity of LDL and Unfavorable Adipokine Profile in Metabolically Obese, Normal-weight Woman

Objective: The relationship of visceral adiposity with adipocytokines and low‐density lipoprotein (LDL) particle distribution and oxidation in Asian metabolically obese, normal‐weight (MONW) individuals has not been evaluated. We aimed to investigate the association between visceral adiposity and adipocytokines and cardiovascular disease (CVD) risk factors in MONW Korean women with normal glucose tolerance.

The influence of the adiponectin gene on adiponectin concentrations and parameters of metabolic syndrome in non-diabetic Korean women

BACKGROUND Concentrations of adiponectin, the protein product of the adipocyte C1q and collagen-domain-containing (ADIPOQ) gene are associated with type 2 diabetes and coronary artery disease. We investigate the association of single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene with adiponectin concentrations, and to parameters of metabolic syndrome. METHODS 867 unrelated, non-diabetic Korean women, 20 to 69 y, were genotyped for 8 SNPs in the ADIPOQ gene (-11391G>A, -11377C>G, H241P, Y111H, G90S, R221S, 45T>G, 276G>T). Adiponectin, a homeostasis model assessment of insulin resistance (HOMA-IR), and metabolic parameters were measured. RESULTS Carriers of genotype T/T at position 276 had significantly higher adiponectin concentrations than G/G carriers (P=0.005). Homozygous carriers of the TG haplotype (i.e., individuals who were T/T at 45 and G/G at 276) and heterozygous carriers of the TG haplotype (TG/X) had lower adiponectin concentrations than non-TG carriers (P<0.001). Significant associations between SNP at 276 and serum concentrations of triglyceride (P=0.013), insulin (P=0.013) and HOMA-IR (P=0.012) were found. The 45-276 haplotypes had associations identical to the 276G>T SNP. In subgroup analysis, subjects carrying the TG haplotype had significantly lower adiponectin concentrations than non-TG carriers in both normal weight (P<0.001) and overweight-obese (P=0.009) subgroups. The association of the TG haplotype with increasing insulin concentrations was significant among overweight-obese subjects (P=0.004), but was not significant among normal weight subjects. A similar association was found between the 45-276 haplotype and HOMA-IR. CONCLUSION There is a strong association of the adiponectin SNP276 genotypes and the adiponectin 45-276 haplotypes with circulating adiponectin concentrations in non-diabetic Korean women. In addition, this haplotype is associated with increased insulin concentrations and insulin resistance index only in overweight-obese individuals.

Influence of Adiponectin Gene Polymorphisms on Adiponectin Level and Insulin Resistance Index in Response to Dietary Intervention in Overweight-Obese Patients With Impaired Fasting Glucose or Newly Diagnosed Type 2 Diabetes

OBJECTIVE The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes. RESEARCH DESIGN AND METHODS A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and −11377) were examined in these subjects. RESULTS After this dietary intervention, fasting glucose levels decreased in all three SNP 45T>G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype. CONCLUSIONS ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention.

The RANTES -403G > A promoter polymorphism in Korean men : association with serum RANTES concentration and coronary artery disease

In the present study we investigated the association of the RANTES (regulated upon activation, normal T-cell expressed and secreted) -28C>G and -403G>A promoter polymorphisms with the concentration of serum RANTES and CAD (coronary artery disease) in Korean men. We included 553 male CAD patients with (n=176) or without (n=377) Type 2 diabetes, aged 40-65 years with previous myocardial infarction ( approximately 50%) or angiographically confirmed CAD ( approximately 50%), and 416 aged-matched healthy male controls. The main outcome measures were the OR (odds ratio) of CAD risk and the serum RANTES concentration evaluated by sandwich ELISA. Although the RANTES -28C>G genotype had no significant association with CAD risk, the presence of the minor allele of the RANTES -403G>A single nucleotide polymorphism was associated with a lower risk of CAD {OR 0.70 [95% CI (confidence interval) 0.54-0.92], P=0.011} after adjusting for age, BMI (body mass index), cigarette smoking and alcohol consumption. Serum RANTES concentrations were significantly associated with the -403G>A genotype in controls (G/G: 44.7+/-3.3 ng/ml, G/A: 36.5+/-2.0 ng/ml, A/A: 28.7+/-2.5 ng/ml; P<0.001), non-diabetic CAD patients (G/G: 50.9+/-3.0 ng/ml, G/A: 42.2+/-2.6 ng/ml, A/A: 41.3+/-4.4 ng/ml; P<0.05) and diabetic CAD patients (G/G: 58.5+/-3.5 ng/ml, G/A: 49.6+/-4.1 ng/ml, A/A: 42.2+/-4.3 ng/ml; P<0.05); however, such associations were not observed in the subgroup of CAD patients taking lipid-lowering medication. Moreover, serum RANTES was positively correlated with C-reactive protein (r=0.289, P<0.001) and platelet counts (r=0.253, P<0.001). The results of the present study demonstrate that the RANTES -403A allele is associated with lower serum RANTES concentrations and consequently with reduced CAD risk.

Association of apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men

OBJECTIVE Whereas the relation between apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting of a case-control study involving Korean males. METHODS ApoA5, TG, insulin, free fatty acid (FFA) and lipoprotein profiles were determined using a cross-sectional design in 777 healthy controls and 367 CAD patients. RESULTS Plasma apoA5 concentration was lower in CAD patients than controls (192.7+/-5.2 vs. 237.2+/-3.7ng/ml, P<0.001). Values in the second and top tertiles of apoA5 were associated with a decreased odds ratio (OR) for CAD when compared with values in the bottom tertile; OR for apoA5 top tertile was 0.33 (95% CI, 0.23-0.47) in the age- and BMI-adjusted model and 0.35 (95% CI, 0.23-0.56) following additional adjustments for smoking, drinking status, blood pressure, TG and HDL-cholesterol. After adjustment for age and BMI, plasma apoA5 concentration was negatively correlated with serum TG (r=-0.188, P<0.001) and insulin (r=-0.185, P<0.001) in normotriglyceridemic controls (TG<150mg/dL, n=509) whereas apoA5 was positively correlated with serum TG in hypertriglyceridemic controls (TG> or =150mg/dL, n=268) (r=0.246, P<0.001) and total CAD patients (r=0.177, P<0.01). Regardless of TG levels and CAD status, apoA5 concentration was positively correlated with HDL-cholesterol and FFA levels. CONCLUSIONS Our data supports an inverse association between plasma apoA5 concentrations and CAD risk, probably due to the observed negative correlations of apoA5 with TGs and insulin, although these correlations were affected by TG levels.

Interleukin‐6 (IL‐6) –572C→G promoter polymorphism is associated with type 2 diabetes risk in Koreans

Objective  Increased levels of inflammatory markers, such as interleukin‐6 (IL‐6), are associated with type 2 diabetes (T2DM). We investigated the association of IL‐6 gene polymorphisms with T2DM and circulating levels of IL‐6 in Koreans.

Interleukin-6-572C>G polymorphism—association with inflammatory variables in Korean men with coronary artery disease

Growing evidence suggests that polymorphisms at position -174 and -572 in interleukin-6 (IL-6) gene are associated with various manifestations of atherosclerosis. We investigated the genotype effects of IL-6 -174 and -572 polymorphisms on circulating levels of inflammatory markers in Korean men with coronary artery disease (CAD). CAD patients were subdivided into 2 groups; those patients treated without lipid-lowering drug (LLD) (n = 173) and those treated with LLD (n = 353). No significant differences existed between the 2 groups in age, body mass index, blood pressure, serum glucose, alcohol consumption, cigarette smoking, and the proportions of antihypertensive and antiplatelet therapies. IL-6 - 572 C>G polymorphism was only observed in this population. In CAD patients not taking LLD, the G/G genotype of the -572C>G polymorphism was associated with greater concentrations of IL-6 (C/C: 4.1 +/- 0.8 pg/mL, C/G: 3.7 +/- 0.7, G/G: 12.4 +/- 6.6; P = 0.031), C-reactive protein (CRP) (C/C: 1.9 +/- 0.4 mg/dL, C/G: 2.7 +/- 0.8, G/G: 10.1 +/- 3.9; P = 0.002), fibrinogen (C/C: 334 +/- 6 mg/dL, C/G: 345 +/- 13, G/G: 429 +/- 38; P = 0.003), and oxidized low-density lipoprotein (ox-LDL) (C/C: 59 +/- 2 mg/dL, C/G: 55 +/- 3, G/G: 71 +/- 6; P = 0.041) than those with C/C or C/G. However, in the LLD group, no difference existed in circulating levels of IL-6, CRP, fibrinogen, and ox-LDL across the genotype after adjustment of age. This study suggests that circulating levels of IL-6 and its related proteins such as CRP and fibrinogen are associated with genotype at a promoter polymorphism (-572C>G) of the IL-6 gene in Korean men with CAD not taking LLD. LLD, mostly statin in this study, might reduce the exaggeration of G/G genotype-raising effect on inflammatory markers.

Association of serum RANTES concentrations with established cardiovascular risk markers in middle-aged subjects.

BACKGROUND RANTES (regulated upon activation, normal T cells expressed and secreted) is known to be related to an inflammatory part of the atherosclerotic process. We investigated the association of serum concentrations of RANTES with the risk of coronary artery disease (CAD) in a case-control study. METHODS One hundred fifty one CAD male patients aged 40 to 65 years and 151 age-matched healthy male controls were included and the main outcome measure was the odds ratio (OR) for CAD associated with increased levels of RANTES. RESULTS Serum levels of RANTES were higher in CAD patients when compared with controls (47.1+/-1.57 ng/mL vs 37.3+/-1.48; P<0.001). In addition, values in the second and top tertile of RANTES were associated with an increased OR for CAD when compared with values in the bottom tertile; OR for RANTES top tertile was 2.86 (95% CI, 1.53 to 5.34) in the age- and WHR-adjusted model and 3.23 (95% CI, 1.02 to 10.3) after the fully adjustment. Furthermore, there was a positive correlation of serum RANTES with acute phase proteins such as hs-CRP (r=0.310, P<0.001) and fibrinogen (r=0.333, P<0.001). RANTES concentrations also displayed a moderate correlation of WHR, triglyceride, HDL-cholesterol, interleukin-1 beta, interleukin-6, adiponectin, platelet and white blood cell counts. CONCLUSION In the present study, RANTES is associated with CAD risk in middle-aged subjects.