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1.  Serum HBV Surface Antigen Positivity is Associated With Low Prevalence of Metabolic Syndrome in Korean Adult Men 
Journal of Epidemiology  2015;25(1):74-79.
Metabolic syndrome has clinical implications for chronic liver disease, but the relationship between chronic hepatitis B and metabolic syndrome remains unclear. The aim of this study was to determine whether hepatitis B surface antigen (HBsAg) positivity is associated with metabolic syndrome.
Data were obtained from the Third Korean National Health and Nutrition Examination Survey (KNHANES). Participant sera were tested for HBsAg. Metabolic syndrome was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III guidelines for Koreans.
Of the 5108 participants, 209 (4.1%) tested positive for HBsAg, and 1364 (26.7%) were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome was 23.4% in HBsAg-positive men, 31.5% in HBsAg-negative men, 18.6% in HBsAg-positive women, and 23.7% in HBsAg-negative women. After adjusting for multiple factors, male participants who tested positive for serum HBsAg had an odds ratio of 0.612 (95% confidence interval [CI] 0.375–0.998) for metabolic syndrome and an odds ratio of 0.631 (95% CI 0.404–0.986) for elevated triglycerides. Women who tested positive for serum HBsAg had an odds ratio of 0.343 (95% CI 0.170–0.693) for elevated triglycerides.
Positive results for serum HBsAg are inversely associated with metabolic syndrome in men and with elevated triglycerides in men and women. This suggests that elevated triglycerides may contribute to the inverse association between HBsAg and metabolic syndrome.
PMCID: PMC4275441
chronic hepatitis B; metabolic syndrome; survey; triglycerides
2.  Impact of Visceral Fat on Skeletal Muscle Mass and Vice Versa in a Prospective Cohort Study: The Korean Sarcopenic Obesity Study (KSOS) 
PLoS ONE  2014;9(12):e115407.
Sarcopenia and visceral obesity have been suggested to aggravate each other, resulting in a vicious cycle. However, evidence based on prospective study is very limited. Our purpose was to investigate whether visceral fat promotes a decrease in skeletal muscle mass and vice versa.
We observed changes in anthropometric and body composition data during a follow-up period of 27.6±2.8 months in 379 Korean men and women (mean age 51.9±14.6 years) from the Korean Sarcopenic Obesity Study (KSOS). Appendicular lean soft tissue (ALST) mass was calculated using dual-energy X-ray absorptiometry, and visceral fat area (VFA) was measured using computed tomography at baseline and follow-up examination.
ALST mass significantly decreased, whereas trunk and total fat mass increased in both men and women despite no significant change in weight and body mass index. In particular, women with visceral obesity at baseline had a greater decrease in ALST mass than those without visceral obesity (P = 0.001). In multiple linear regression analysis, baseline VFA was an independent negative predictor of the changes in ALST after adjusting for confounding factors including age, gender, life style and body composition parameters, insulin resistance, high sensitivity C-reactive protein and vitamin D levels (P = 0.001), whereas the association between baseline ALST mass and changes in VFA was not statistically significant (P = 0.555).
This longitudinal study showed that visceral obesity was associated with future loss of skeletal muscle mass in Korean adults. These results may provide novel insight into sarcopenic obesity in an aging society.
PMCID: PMC4269440  PMID: 25517117
3.  Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats 
Diabetes & Metabolism Journal  2013;37(5):358-364.
Interleukin-15 (IL-15), a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models.
Male Zucker diabetic fatty (ZDF) and ZDF lean control (ZLC) rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL) and gastrocnemius medial muscles.
After 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01) only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04).
The present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.
PMCID: PMC3816137  PMID: 24199165
Exercise; Glucose intolerance; Interleukin-15; Rats, Zucker; Treadmill
4.  Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson’s rats 
Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson’s disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson’s rats. Parkinson’s rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection group exhibited significant rotational asymmetry following apomorphine challenge. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the present results, extensive degeneration of the dopaminergic neurons in the substantia nigra with loss of dopaminergic fibers in the striatum were produced in the rats without treadmill running, which resulted in short-term memory impairment. However, the rats performing treadmill running for 2 weeks alleviated nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment with increasing cell proliferation in the hippocampal dentate gyrus of Parkinson’s rats. The present results show that treadmill exercise may provide therapeutic value for the Parkinson’s disease.
PMCID: PMC3836534  PMID: 24278884
Parkinson’s rats; 6-Hydroxydopamine; Treadmill exercise; Cell proliferation; Apoptosis
5.  Effect of HX108-CS supplementation on exercise capacity and lactate accumulation after high-intensity exercise 
In the present study, we determined the effects of HX108-CS (mixed extract of Schisandra chinensis and Chaenomeles sinensis) supplementation on lactate accumulation and endurance capacity. Furthermore, we examined CK (creatine kinase), LDH (lactate dehydrogenase) activity to determine whether the HX108-CS affected markers of skeletal muscle injury in vivo and in vitro.
Exercise capacity was measured by an exhaustive swimming test using ICR mice divided into four groups; one group received distilled water (DW) (Control group, n = 10), and the other groups received three different dosages of HX108-CS (10, 50 and 100 mg/kg, n = 10 per group) solution in water orally. Then, for the time-dependent measurements of blood lactate, CK, and LDH, Sprague–Dawley rats were divided into two groups; one received DW (Control group, n = 10), and the other group received HX108-CS (100 mg/kg, n = 10) solution in the same way as mice. Before the exercise test, the animals were given either DW or HX108-CS for 2 weeks. High-intensity treadmill exercise was performed for 30 minutes. Blood samples were collected and analyzed during and after exercise. For the in vitro experiment, C2C12 cells were treated with HX108-CS to examine its effect on lactate production, CK, and LDH activity.
Blood lactate concentration was significantly lowered immediately after treadmill exercise in HX108-CS group; however, there were no significant differences in activities of CK and LDH between HX108-CS and control during treadmill exercise and recovery phase. Furthermore, treatment with 100 mg/kg of HX108-CS led to a significant increase in the time to exhaustion in swimming test, and concurrently blood lactate concentration was significantly decreased in 50 and 100 mg/kg treated group. Moreover, our results of in vitro experiment showed that HX108-CS suppressed lactate production, CK, and LDH activity in a dose-dependent manner.
These results suggest that supplementation with HX108-CS may enhance exercise capacity by lowering lactate accumulation. This may in part be related to an amelioration of skeletal muscle injury.
PMCID: PMC3659049  PMID: 23587302
HX108-CS; Schisandra chinensis; Chaenomeles sinensis; Endurance capacity; Exercise capacity; Lactate accumulation
6.  Differential effects of treadmill exercise on cyclooxygenase-2 in the rat hippocampus at early and chronic stages of diabetes 
Laboratory Animal Research  2011;27(3):189-195.
Cyclooxygenase-2 (COX-2) is believed to be a multifunctional neural modulator that affects synaptic plasticity in the hippocampus. In the present study, we investigated the differential effects of treadmill exercise on COX-2 immunoreactivity in the dentate gyrus in early and chronic diabetic stages in Zucker diabetic fatty (ZDF) rats and lean control (ZLC) rats. To this end, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day for 5 consecutive days at 16-22 m/min for 5 weeks or 12-16 m/min for 7 weeks, respectively. Treadmill exercise in prediabetic and chronic diabetic rats significantly reduced blood glucose levels. In particular, exercise in the prediabetic rat blocked the onset of diabetes. COX-2 immunoreactivity was mainly detected in the granule cell layer of the dentate gyrus and stratum pyramidale of the CA3 region in all groups. COX-2 immunoreactivity was significantly increased in these regions of ZLC and ZDF rats after treadmill exercise in the early diabetic stage. However, COX-2 immunoreactivity was not changed in these regions in ZDF rats after treadmill exercise in the chronic stage. These results suggest that treadmill exercise in diabetic animals in the chronic stage has limited ability to cause plasticity in the dentate gyrus.
PMCID: PMC3188725  PMID: 21998607
Cyclooxygenase-2; diabetic stages; type 2 diabetes; treadmill exercise; Zucker diabetic rat
7.  Prevalence and Determinant Factors of Sarcopenia in Patients With Type 2 Diabetes 
Diabetes Care  2010;33(7):1497-1499.
We examined prevalence of sarcopenia in Korean patients with type 2 diabetes and compared body compositional parameters between subjects with and without type 2 diabetes.
The Korean Sarcopenic Obesity Study (KSOS) included 810 subjects (414 patients with diabetes and 396 control subjects) who were examined using dual-energy X-ray absorptiometry. Prevalence of sarcopenia was defined using the skeletal muscle index (SMI).
Prevalence in patients with diabetes and in the control group was 15.7 and 6.9%, respectively. In both men and women, SMI values were significantly decreased in patients with diabetes compared with subjects without diabetes. Furthermore, multiple logistic regression analysis showed that type 2 diabetes was independently associated with sarcopenia.
Type 2 diabetes was associated with increased risk of sarcopenia. These characteristics may contribute to physical disability and metabolic disorders in older adults with diabetes.
PMCID: PMC2890348  PMID: 20413515
8.  Overexpression of Mn Superoxide Dismutase Does Not Increase Life Span in Mice 
Genetic manipulations of Mn superoxide dismutase (MnSOD), SOD2 expression have demonstrated that altering the level of MnSOD activity is critical for cellular function and life span in invertebrates. In mammals, Sod2 homozygous knockout mice die shortly after birth, and alterations of MnSOD levels are correlated with changes in oxidative damage and in the generation of mitochondrial reactive oxygen species. In this study, we directly tested the effects of overexpressing MnSOD in young (4–6 months) and old (26–28 months) mice on mitochondrial function, levels of oxidative damage or stress, life span, and end-of-life pathology. Our data show that an approximately twofold overexpression of MnSOD throughout life in mice resulted in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production. However, this change in MnSOD expression did not alter either life span or age-related pathology.
PMCID: PMC2759571  PMID: 19633237
Oxidative damage; Mn superoxide dismutase; Pathology; Aging
9.  Glutathione Peroxidase 4 Differentially Regulates the Release of Apoptogenic Proteins from Mitochondria 
Free radical biology & medicine  2009;47(3):312-320.
Glutathione peroxidase 4 (Gpx4) is a unique antioxidant enzyme that repairs oxidative damage to biomembranes. In the present study, we examined the effect of Gpx4 on the release of various apoptogenic proteins from mitochondria using transgenic mice overexpressing Gpx4 [Tg(GPX4+/0)] and mice deficient in Gpx4 (Gpx4+/− mice). Diquat exposure triggered apoptosis that occurred through intrinsic pathway and resulted in the mitochondrial release of cytochrome c (cyt. c), Smac/DIABLO, and Omi/HtrA2 in the liver of wild-type (Wt) mice. Liver apoptosis and cyt. c release were suppressed in Tg(GPX4+/0) mice but exacerbated in Gpx4+/− mice; however, neither the Tg(GPX4+/0) nor the Gpx4+/− mice showed any alterations in the levels of Smac/DIABLO or Omi/HtrA2 released from mitochondria. Submitochondrial fractionation data showed that Smac/DIABLO and Omi/HtrA2 existed primarily in the intermembrane space and matrix, while cyt. c and Gpx4 were both associated with inner membrane. In addition, diquat exposure induced cardiolipin peroxidation in the liver of Wt mice; the levels of cardiolipin peroxidation were reduced in Tg(GPX4+/0) mice but elevated in Gpx4+/− mice. These data suggest that Gpx4 differentially regulates apoptogenic protein release due to its inner membrane location in mitochondria and its ability to repair cardiolipin peroxidation.
PMCID: PMC2773016  PMID: 19447173
Gpx4; Phospholipid hydroperoxide glutathione peroxidase 4; Apoptosis; Cardiolipin; Lipid peroxidation; Oxidative stress
10.  Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery 
Experimental physiology  2009;95(1):222-231.
Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force–frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm−2) at stimulation frequencies of 20–300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in μm2) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with contractile dysfunction. Finally, the transgenic overexpression of independent endogenous antioxidants alters diaphragm skeletal muscle morphology, and these changes may also contribute to the diminished specific force production observed in these animals.
PMCID: PMC2910396  PMID: 19783618
11.  Exercise Training Modulates the Nitric Oxide Synthase Profile in Skeletal Muscle From Old Rats 
The effects of exercise training on the nitric oxide synthase (NOS) isoform profile in aging fast-twitch (white gastrocnemius [WG]) and slow-twitch (soleus [SOL]) muscle have not been investigated. Six-month and 27-month male Fischer-344 rats were divided into the following groups: young sedentary (YS), young treadmill exercise trained for 12 weeks, old sedentary (OS), and old exercise trained (OE). Inducible NOS (iNOS) protein expression and activity were significantly higher in OS compared with YS, whereas exercise training significantly reduced iNOS protein and activity levels in the WG. Neuronal NOS protein expression decreased with aging in WG but was upregulated significantly with exercise training in OE for both WG and SOL. Endothelial NOS (eNOS) protein levels were depressed in WG of old rats but were higher in OE than in OS. eNOS was unaffected by aging or exercise in the SOL. Our results indicate that endurance exercise training attenuates age-induced alterations of NOS isoforms with a greater response in fast-twitch compared with slow-twitch muscle.
PMCID: PMC2800810  PMID: 19304939
Aging; Skeletal muscle; Exercise; Nitric oxide synthase; nNOS; eNOS; iNOS
12.  A Case of Huge Thrombus in the Aortic Arch with Cerebrovascular Embolization 
Pedunculated thrombus in the aortic arch that is associated with cerebral infarction is very rare requires prompt diagnosis and treatment to prevent occurrence of another devastating complication. Transesophageal echocardiography is useful for detecting source of embolism including aortic thrombi. The treatment options of aortic thrombi involves anticoagulation, thrombolysis, thromboaspiration, and thrombectomy. Here we report a case of huge thrombus in the aortic arch, resulting in acute multifocal cerebellar embolic infarct in patient without any risk factors for vascular thrombosis. Thrombi in the aortic arch were diagnosed by transesophageal echocardiography and treated with anticoagulants successfully.
PMCID: PMC2889393  PMID: 20661342
Aortic thrombus; Echocardiography
13.  Comparison of Lactate Threshold, Glucose, and Insulin Levels Between OLETF and LETO Rats After All-Out Exercise 
Otsuka Long-Evans Tokushima Fatty (OLETF) rats are an animal model for obesity and Non Insulin Dependent Diabetes Mellitus by hyperphagia. The lactate threshold (LT) is used to determinate aerobic capacity and exercise intensity in individuals. The purpose of this study was to determine whether velocity at the LT (VLT), glucose, and insulin levels of OLETF differs from Long-Evans Tokushima (LETO) rats after all-out exercise on treadmill running. In the results, we found that VLT level of OLETF rats (17.8 ± 1.39 m·min-1) was significantly lower than that of the LETO rats (20.5 ± 1.33 m·min-1). The blood glucose levels immediately after all-out exercise increased in OLETF (from 7.23 ± 0.36 to 9.38 ± 1.77 mmol·L-1) and decreased in LETO rats (from 6.36 ± 0.27 to 4.42 ± 0.71 mmol·L-1), and the insulin level was decreased in both the OLETF (from 34.4 ± 7.7 to 20.13 ± 8.63 µU·mL-1) and LETO (from 15.29 ± 2.6 to 5.72 ± 1.49 µU·mL-1) rats immediately after the all-out exercise, but the difference was not significant. Our results suggest that the different VLT, blood glucose and insulin levels should be considered to compensate for the differences between the OLETF and LETO rats. Moreover, the VLT will be a useful reference for the future studies on exercise training of OLETF rats.
Key pointsThe VLT of OLETF was significantly lower than that of LETO rats.The changes of the blood lactate levels from rest to all-out exercise showed significant difference between OLETF and LETO rats.The result of low VLT in the OLETF compared to LETO rats implies that the application of relatively low exercise intensity is suitable for OLETF rats.The different VLT should be recognized to compensate for the differences between the OLETF and LETO rats.
PMCID: PMC3763283  PMID: 24150001
NIDDM; OLETF; treadmill running; all-out exercise; lactate; velocity of lactate threshold

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