Hyun-Sik Kang

Lifestyle plus Exercise Intervention Improves Metabolic Syndrome Markers without Change in Adiponectin in Obese Girls

Background/Aims: Little is known about whether lifestyle plus exercise intervention improves obesity, metabolic syndrome markers, and circulating adiponectin concentrations in obese girls. The goal of this study was to investigate the effects of a 12-week lifestyle plus exercise intervention on adiponectin and metabolic syndrome markers in Korean obese adolescents. Methods: A total of 44 obese adolescent girls (13–15 years old), who were recruited from a local middle school via a flyer or a school newsletter, were randomized to a lifestyle plus exercise intervention group (LIFE+EX, n = 22) or control (CON, n = 22). The LIFE+EX group participated in 12 weeks of lifestyle plus exercise intervention, while the CON group maintained their lifestyle as usual. Body composition, metabolic syndrome markers, and adiponectin were measured prior to and after the intervention program. Results: Following the 12-week lifestyle plus exercise intervention, group analyses showed significant time × group interactions in changed scores in several of the metabolic syndrome markers such that the LIFE+EX group had significantly greater improvements in body composition including body weight, body mass index, percent body fat, waist circumference, and waist-to-hip ratio than the CON group. Similarly, the LIFE+EX group had significantly greater reductions in SBP, TC, LDLC, TG, TC/HDLC, glucose, insulin, HOMA-IR, CRP, and leptin than the CON group, while there were no significant time × group or time or group differences in DBP, HDLC, HbA1c, and adiponectin. Conclusion: The current findings suggest that lifestyle plus exercise intervention may be an effective means to improve several variables in the health hazards of obesity in Korean adolescent girls, with no change in circulating adiponectin.

Antidepressant effects of exercise are produced via suppression of hypocretin/orexin and melanin-concentrating hormone in the basolateral amygdala

Physical exercise is considered beneficial in the treatment of depression, but the underlying mechanism is not clearly understood. In the present study, we investigated the mechanism regulating antidepressant effects of exercise by focusing on the role of the amygdala using a well-defined animal model of depression. C57BL/6 mice treated with repeated restraint showed depression-like behaviors, which was counteracted by post-stress treatment with physical exercise. The two neuropeptides hypocretin/orexin (Hcrt/Orx) and melanin-concentrating hormone (MCH) were transcriptionally upregulated in the BLA after repeated stress, and their enhanced expression was downregulated by treatment with exercise, mirroring stress-induced depression-like behaviors and their reversal by exercise. Stereotaxic injection of either Hcrt/Orx peptide or MCH peptide within the BLA commonly increased phospho-CaMKIIα level and produced depression-like behaviors, mimicking the neural states in the BLA of mice subjected to repeated stress. In contrast, siRNA-mediated suppression of Hcrt/Orx or MCH in the BLA blocked stress-induced depression-like behaviors. Furthermore, siRNA-mediated inhibition of CaMKIIα in the BLA also counteracted stress-induced depression-like behaviors. Local injection of Hcrt/Orx peptide or MCH peptide within the BLA in exercise-treated animals blocked antidepressant-like effects of exercise. Together these results suggest that exercise produces antidepressant effects via suppression of Hcrt/Orx and MCH neural systems in the BLA.

Effect of walking exercise on abdominal fat, insulin resistance and serum cytokines in obese women

[Purpose] The purpose of the study was to investigate the effect of 12-week walking exercise on abdominal fat, insulin resistance and serum cytokines in obese women. [Methods] Following baseline measurements, obese women (N = 20) who met obesity criterion of BMI at 25 kg/m2 or greater were randomly assigned to the control (n = 10) or exercise groups (n = 10). Women assigned to the exercise group participated in a walking exercise (with an intensity of 50-60% of predetermined VO2max, a frequency of 3 days per week and duration of 50-70 minutes targeting 400 kcal of energy expenditure per session) for 12 weeks, while women assigned to the control group maintained their sedentary lifestyle. After the 12-week walking intervention, post-test measurements were conducted using the same procedure as the baseline measurement. Analyses of variance with repeated measures were used to evaluate any significant time by group interactions for the measured variables. [Results] With respect to body fat parameters, significant time-by-group interactions were found in the abdominal subcutaneous (p = < 0.001) and visceral adipose tissues (p = 0.011). The exercise group had significant reductions in both subcutaneous and visceral adiposity, and the control group had no significant changes in those parameters. Similarly, there were significant time by group interactions in fasting glucose (p = 0.008), HOMA-IR (p = 0.029), serum TNF-α (p = 0.027), and IL-6 (p = 0.048) such that the exercise group had significant reductions in those parameters, with no such significant changes found in the control group. The exercise group also had a significant increase in serum adiponectin (p = 0.002), whereas the control group had no significant change in the parameter. [Conclusion] In summary, the current findings suggest that walking exercise can provide a safe and effective lifestyle strategy against abdominal obesity and serum insulin resistance markers in obese women.

Effect of Training Intensity on Nonalcoholic Fatty Liver Disease.

BACKGROUND Training intensity may play a key role in magnifying the protective effect of physical exercise against nonalcoholic fatty liver disease (NAFLD). PURPOSE This study aimed to test the hypothesis that vigorous-intensity and interval training is as effective as moderate-intensity and continuous exercise training on NAFLD in high-fat diet (HFD)-induced obese mice. METHODS C57BL/6 mice (N = 40) were fed a standard-chow diet (n = 10) or HFD (n = 30) for 16 wk. After the initial 8-wk dietary treatments, HFD mice were further divided into HFD only (n = 10), HFD plus vigorous-intensity and interval treadmill running (VIT) (n = 10), and HFD plus moderate-intensity and continuous treadmill running (MIT) (n = 10) for the remaining 8-wk period. RESULTS Chronic exposure to HFD resulted in hepatic steatosis in conjunction with an obese and impaired glucose tolerance condition characterized by dyslipidemia, hyperinsulinemia elevated markers for the liver damage, and hypoadiponectinemia. Although VIT and MIT alleviated the NAFLD conditions, the former was more effective at alleviating hepatic steatosis than the latter. The intensity-dependent benefit of exercise training against hepatic steatosis was associated with greater activation of VIT on hepatic AMP-mediated protein kinase in conjunction with greater suppressive effect of VIT on hypoadiponectinemia, downregulation of the Adiponectin receptor 2 signaling pathway, and upregulation of the NF-κB signaling pathway in the liver. CONCLUSIONS The current findings suggest that VIT is an alternative way of exercise training to combat hepatic steatosis associated with an obese and impaired glucose tolerance phenotype.

Effect of aerobic exercise training on non-alcoholic fatty liver disease induced by a high fat diet in C57BL/6 mice

[Purpose] The aim of this study was to investigate the effects of aerobic exercise training on a high fat diet (HFD)-induced fatty liver and its metabolic complications in C57BL/6 mice. [Methods] Mice at 5-month old (n = 30) were randomly assigned to standard chow (SC + CON, n = 10) and high-fat diet (HFD, n = 20), and they were subjected to SC and HFD, respectively, for 23-week. After 15-week of HFD, mice in the HFD group were further assigned to HFD (HFD + CON, n = 10) or exercise training (HFD + EX, n = 10) groups. The HFD + EX mice were subjected to aerobic treadmill running during the last 8-week of the 23-week HFD course. Outcomes included hepatic steatosis, insulin resistance, and expression of genes involved in mitochondrial function and/or fatty oxidation as well as de novo lipogenesis and/or triacylglycerol (TAG) synthesis. [Results] Treadmill running ameliorated impaired glucose tolerance and insulin resistance secondary to the HFD. The beneficial effects of treadmill running were associated with enhanced molecular markers of mitochondrial function and/or fatty acids oxidation (i.e., PPARα and CPT1a mRNAs, pAMPK/AMPK, pACC, and SIRT1 protein) as well as suppressed expression of de novo lipogenesis and/or TAG synthesis (i.e., SREBP1c, lipin1 and FAS mRNAs) in the liver. [Conclusion] The current findings suggest that aerobic exercise training is an effective and non-pharmacological means to combat fatty liver and its metabolic complications in HFD-induced obese mice.

Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease.

PURPOSE This study investigated the effect of treadmill running on cognitive declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD mice. METHODS At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg-AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The AD + EX mice were subjected to treadmill running for 12 wk. At each pathological stage, the background strain mice were included as wild-type control (WT + CON, n = 8-12). RESULTS At the early stage of AD, 3xTg-AD mice had impaired short- and long-term memory based on Morris water maze along with higher cortical Aβ deposition, higher hippocampal and cortical tau pathology, and lower hippocampal and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the tau pathology along with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long-term memory along with higher levels of Aβ deposition, soluble Aβ1-40 and Aβ1-42, tau pathology, and lower levels of brain-derived neurotrophic factor, PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the Aβ and tau pathology along with suppression of the decreased synaptic proteins and brain-derived neurotrophic factor in the hippocampus and cortex. CONCLUSIONS The current findings suggest that treadmill running provides a nonpharmacological means to combat cognitive declines due to AD pathology.

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

Schizophrenia is a chronic and severe mental disorder characterized by the disintegration of cognitive thought processes and emotional responses. Despite the precise cause of schizophrenia remains unclear, it is hypothesized that a dysregulation of the N‑methyl‑D‑aspartate (NMDA) receptor in the brain is a major contributing factor to its development. Brain‑derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is implicated in learning and memory processes. In the present study, we investigated in vivo the effects of voluntary wheel running on behavioral symptoms associated with NMDA receptor expression, using MK‑801‑induced schizophrenic mice. Abilify (aripiprazole), a drug used to treat human schizophrenia patients, was used as the positive control. For the assessment of behavioral symptoms affecting locomotion, social interaction and spatial working memory, the open‑field, social interaction and Morris water maze tests were conducted. For investigating the biochemical parameters, NMDA receptor expression in the hippocampal CA2‑3 regions and prefrontal cortex was detected by NMDA immunofluorescence and BDNF expression in the hippocampus was measured using western blot analysis. MK‑801 injection for 14 days induced schizophrenia‑like behavioral abnormalities with decreased expression of the NMDA receptor and BDNF in the brains of mice. The results indicated that free access to voluntary wheel running for 2 weeks alleviated schizophrenia‑like behavioral abnormalities and increased the expression of NMDA receptor and BDNF, comparable to the effects of aripiprazole treatment. In the present study, the results suggest that NMDA receptor hypofunctioning induced schizophrenia‑like behaviors, and that voluntary wheel running was effective in reducing these symptoms by increasing NMDA receptor and BDNF expression, resulting in an improvement of disease related behavioral deficits.

Serum Vitamin D, Physical Activity, and Metabolic Risk Factors in Korean Children.

PURPOSE The purpose of this study was to investigate the relationship of serum vitamin D levels with lifestyle factors, including body fatness and physical activity (PA) parameters, and the clustering of metabolic risk factors in the Korean pediatric population. METHODS Serum 25-hydroxyvitamin D levels, accelerometer-based PA, and body fatness and metabolic syndrome parameters were assessed in a sample of children of Korean descent (N = 310). Correlation and multivariate linear regression were used to explore the relationships among serum vitamin D levels, lifestyle factors, and the clustering of metabolic risk factors in the study sample. RESULTS Serum vitamin D levels were negatively associated with body fatness parameters, including body mass index, percent body fat, and waist circumference, but positively associated with accelerometer-based PA including low, moderate, and vigorous levels. In addition, serum vitamin D levels were inversely related to total cholesterol, triglycerides, fasting glucose, and insulin. A stepwise linear regression model showed that both low serum vitamin D levels and decreased vigorous PA were independent predictors for individual variation in the clustering of metabolic risk factors in this study sample. CONCLUSION The results of this study suggest that an increase in vigorous PA and vitamin D intake should be two major targets of public health inventions against the clustering of metabolic risk factors in the Korean pediatric population.

The apolipoprotein CIII T2854G variants are associated with postprandial triacylglycerol concentrations in normolipidemic Korean men

AbstractThis study investigated associations between the apolipoprotein (apo) CIII polymorphism and triacylglycerol (TAG) concentrations in fasting and postprandial plasma. Polymerase chain reaction followed by a restriction fragment length genotyping was conducted to assess the allele frequency of the apo CIII T2854G variants in healthy and normolipidemic Korean men (n=262). Waist circumference, body mass index (kilograms per meter squared), fasting plasma concentrations of TAG, total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), glucose, and insulin were compared across the genotypes. Compared to TT homozygotes and TG heterozygotes, GG homozygotes had 22% higher fasting TAG concentrations, respectively (p<0.05). A subgroup of 60 subjects (TT homozygotes=20, TG heterozygotes=22, GG homozygotes= 18) were further invited to participate in a high-fat meal test to assess postprandial TAG concentrations. During the high-fat meal test, the GG homozygotes had 21% higher TAG area under the curve (AUC) than the TT homozygotes (p<0.05) and 22% higher TAG AUC than the TG heterozygotes (p<0.05). In conclusion, this is the first study to show that the apo CIII T2854G variants are associated with elevated postprandial TAG concentrations in the study population of Korean men.

Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene.