Jong-Youn Kim

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.

Cocoa polyphenols suppress adipogenesis in vitro and obesity in vivo by targeting insulin receptor.

Objective:To investigate the inhibitory effect of cocoa polyphenol extract (CPE) on adipogenesis and obesity along with its mechanism of action.Methods and Results:3T3-L1 preadipocytes were cultured with isobutylmethylxanthine, dexamethasone and insulin (MDI), and male C57BL/6N mice (N=44) were fed a high-fat diet (HFD) for 5 weeks with or without CPE. CPE at 100 or 200 μg ml−1 inhibited MDI-induced lipid accumulation without diminishing cell viability. In particular, CPE reduced the protein expression levels of PPARγ and CEBPα, and blocked mitotic clonal expansion (MCE) of preadipocytes by reducing proliferating signaling pathways. This in turn attenuates lipid accumulation during the differentiation of 3T3-L1 preadipocytes. CPE effectively suppressed MDI-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and their downstream signals. We then examined whether CPE regulates insulin receptor (IR), a common upstream regulator of ERK and Akt. We found that although CPE does not affect the protein expression level of IR, it significantly inhibits the activity of IR kinase via direct binding. Collectively, the results suggested that CPE, a direct inhibitor of IR kinase activity, inhibits cellular differentiation and lipid accumulation in 3T3-L1 preadipocytes. Consistently, CPE attenuated HFD-induced body weight gain and fat accumulation in obese mice fed with a HFD. We also found that HFD-induced increased fasting glucose levels remained unaffected by CPE.Conclusion:This study demonstrates that CPE inhibits IR kinase activity and its proliferative downstream signaling markers, such as ERK and Akt, in 3T3-L1 preadipocytes, and also prevents the development of obesity in mice fed with a HFD.

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.

Percutaneous Treatment of Deep Vein Thrombosis in May-Thurner Syndrome

Background/PurposeMay-Thurner syndrome is an uncommon disease entity in which the left common iliac vein is compressed by the right common iliac artery with subsequent development of deep vein thrombosis and chronic venous insufficiency. We report our experience on the treatment of extensive iliofemoral deep venous thrombosis due to May-Thurner syndrome using endovascular techniques.MethodsThe study group comprised 21 patients (8 men, 13 women; mean age 51 years) diagnosed with May-Thurner syndrome by venogram. Eighteen patients were treated with catheter-guided thrombolysis; 3 patients with short segment involvement did not require thrombolysis. After completion of the thrombolytic therapy, the residual venous narrowing was treated by balloon angioplasty and/or placement of a self-expandable stent.ResultsThe mean total dose of urokinase was 4.28 ± 1.89 million units, and the mean duration of infusion was 72 ± 35 hr. Eighteen of the 21 patients received stent deployment. The mean diameter of the stents was 12.9 ± 2.0 mm. Initial technical successes with immediate symptom resolution were achieved in 20 of the 21 patients (95%). We performed a follow-up venogram 6 months after procedure and checked clinical symptoms at outpatient clinics (mean follow-up duration 10.8 months). Among the patients who received stent implantation, 2 had recurrent thrombotic occlusion during the follow-up period. Three patients, who did not receive stent implantation, all had recurrent thrombosis. There were no major bleeding complications except in 1 patient who developed retroperitoneal hematoma.ConclusionCatheter-guided thrombolysis and angioplasty with stent implantation is a safe and effective method for the treatment of May-Thurner syndrome.

Genetic variation at the perilipin locus is associated with changes in serum free fatty acids and abdominal fat following mild weight loss.

Objective:Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss.Methods:Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (−300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F2α (PGF2α) were examined.Results:Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D′=0.923, R 2=0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D′=0.824, R 2=0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F2α and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF2α after weight reduction.Conclusion:Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF2α and oxidized LDL.

Impact of Metabolic Syndrome and Its Individual Components on the Presence and Severity of Angiographic Coronary Artery Disease

Purpose Metabolic syndrome (MS) has been reported as a potential risk factor of coronary artery disease (CAD). The aims of this study were to assess whether there was a relationship between MS score and CAD angiographic severity, and to assess the predictive value of individual components of MS for CAD. Materials and Methods We retrospectively enrolled 632 patients who underwent coronary angiography for suspected CAD (394 men, 61.0 ± 10.6 years of age). MS was defined by the National Cholesterol Education Program criteria with the waist criterion modified into a body mass index (BMI) of more than 25 kg/m2. The MS score defined as the number of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD angiographic severity was evaluated with a Gensini scoring system. Results Of the patients, 497 (78.6%) had CAD and 283 (44.8%) were diagnosed with MS. The MS score was significantly related to the Gensini score. High fasting blood glucose (FBG) was the only predictive factor for CAD. A cluster including high FBG, high blood pressure (BP), and low high-density lipoprotein cholesterol (HDL-C) showed the highest CAD risk. Conclusion The MS score correlates with the angiographic severity of CAD. The predictive ability of MS for CAD was carried almost completely by high FBG, and individual traits with high BP and low HDL-C may act synergistically as risk factors for CAD.

Local increase in microparticles from the aspirate of culprit coronary arteries in patients with ST-segment elevation myocardial infarction.

OBJECTIVE It has been reported that the levels of procoagulant microparticles (MPs) are increased in patients with acute coronary syndromes and this may contribute to the formation of intracoronary thrombi. In the current study, we investigated the presence of locally elevated MPs within the culprit coronary arteries of patients with ST-segment elevation myocardial infarction (STEMI). METHODS The study population consisted of 45 patients with STEMI who underwent primary percutaneous coronary intervention (PCI), and 16 control patients. Before and after PCI, blood samples were collected from the femoral artery and from the culprit coronary arteries. In controls, only peripheral blood was obtained. MPs were measured by a solid-phase capture assay using a commercial kit. The cell origins of MPs were determined by antigenic capture with specific antibodies. RESULTS Baseline levels of MPs in patients with STEMI were higher than in controls. Before PCI, the levels of MPs were significantly higher in culprit coronary arteries than in peripheral arteries in STEMI patients (20.7 ± 15.5 vs. 14.6 ± 15.4 nM phosphatidylserine (PS) equivalent, p = 0.027). MPs from the culprit coronary artery were significantly reduced after PCI (20.7 ± 15.5 vs. 14.3 ± 14.9 nM PS equivalent, p = 0.010). Similarly, the locally increased levels of endothelial- and platelet-derived MPs within the culprit coronary arteries were significantly decreased after PCI. CONCLUSION Locally increased levels of MPs in culprit coronary arteries and their significant reduction after successful PCI suggest a potential role in coronary atherothrombosis in the early period of STEMI.

Incidence and natural history of coronary artery aneurysm developing after drug-eluting stent implantation.

AIMS There is a growing concern about the occurrence of coronary artery aneurysms (CAAs) after drug-eluting stent (DES) implantation and their long-term course. We assessed the occurrence and the factors affecting the long-term outcome of DES-associated CAA. METHODS AND RESULTS We analyzed 3,612 consecutive patients (4,419 lesions) who underwent follow-up angiography after DES implantation. All 34 CAAs (0.76% per lesion) in 29 patients (0.8% per patient) were detected at follow-up, and the mean elapsed time from DES implantation to CAA diagnosis was 414 ± 213 days. Angiographically, CAAs developed almost exclusively in complex (type B2/C) de novo lesions (30 [88.2%] of 34 lesions), and lesion length was significantly greater in patients with CAA than without CAA (26.9 ± 9.03 vs 23.1 ± 7.14 mm; P = .004). Myocardial infarction with stent thrombosis occurred in 5 patients with CAA (17.2%), 4 of whom were on aspirin only without clopidogrel. CONCLUSION Although CAAs rarely develop after DES implantation and show mostly favorable clinical courses, long-term maintenance of clopidogrel therapy might be required to minimize occurrence of adverse clinical events resulting from stent thrombosis.

Expression of interleukin-17 is correlated with interferon-α expression in cutaneous lesions of lupus erythematosus.

Background.  Type I interferon (IFN) has been reported to have an important role in the development of cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). A new subset of CD4+ T cells, T helper (Th)17 cells, also plays a role in the development of autoimmunity.

Effects of Atorvastatin 20 mg, Rosuvastatin 10 mg, and Atorvastatin/Ezetimibe 5 mg/5 mg on Lipoproteins and Glucose Metabolism:

The aim of this study was to compare the effects of 3 different statin regimens that have equivalent low-density lipoprotein cholesterol (LDL-C) lowering efficacy on the apolipoprotein B/A1 ratio and glucose metabolism. After a 4-week dietary lead-in, 90 hypercholeserolemic patients were randomly assigned to 1 of 3 treatment groups for 8 weeks: atorvastatin 20 mg, rosuvastatin 10 mg, or atorvastatin/ezetimibe 5 mg/5 mg. At drug treatment week 8, we compared the percentage changes in lipid parameters, apolipoprotein B/A1 ratio, hemoglobin A1c, and homeostasis model assessment-insulin resistance (HOMA-IR) from baseline. Seventy-six patients completed the study and the percentage changes in LDL-C were comparable among the groups. However, the percentage reduction in the apolipoprotein B/A1 ratio was significantly greater in the rosuvastatin group (—47% ± 14%, P = .04) and the combination group (—46% ± 8%, P = .05) than in the atorvastatin group (—39% ± 11%). The percentage increase in hemoglobin A1c was small but significantly greater in the atorvastatin group compared to the combination group (3.0% ± 5.2% and —0.4% ± 4.0%, P = .03). The effect of rosuvastatin on hemoglobin A1c was not different from those of the other 2 regimens. The effects of 3 statin regimens were similar on HOMA-IR. In conclusion, 3 statin regimens have differential effect on apolipoprotein B/A1 and glycemic control after comparable LDL-C reduction.