Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes

Background@#Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)–peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown. Here, we investigated the role of SENP2 in the regulation of fatty acid metabolism by leptin in adipocytes and white adipose tissues. @*Methods@#The effects of leptin mediated by SENP2 on fatty acid metabolism were tested by siRNA-mediated knockdown in 3T3-L1 adipocytes. The role of SENP2 was confirmed in vivo using adipocyte-specific Senp2 knockout (Senp2-aKO) mice. We revealed the molecular mechanism involved in the leptin-induced transcriptional regulation of carnitine palmitoyl transferase 1b (Cpt1b) and long-chain acyl-coenzyme A synthetase 1 (Acsl1) using transfection/reporter assays and chromatin immunoprecipitation. @*Results@#SENP2 mediated the increased expression of FAO-associated enzymes, CPT1b and ACSL1, which peaked 24 hours after leptin treatment in adipocytes. In contrast, leptin stimulated FAO through AMPK during the initial several hours after treatment. In white adipose tissues, FAO and mRNA levels of Cpt1b and Acsl1 were increased by 2-fold 24 hours after leptin injection in control mice but not in Senp2-aKO mice. Leptin increased PPARα binding to the Cpt1b and Acsl1 promoters in adipocytes through SENP2. @*Conclusion@#These results suggest that the SENP2-PPARα pathway plays an important role in leptin-induced FAO in white adipocytes.

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence

The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

Weight control practices, beliefs, self-efficacy, and eating behaviors in college weight class athletes

Metformin Ameliorates Lipotoxic β-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.RESULTS: We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.CONCLUSION: This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.

Discriminative Effects of Social Skills Training on Facial Emotion Recognition among Children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

OBJECTIVES: This study investigated the effect of social skills training (SST) on facial emotion recognition and discrimination in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). METHODS: Twenty-three children aged 7 to 10 years participated in our SST. They included 15 children diagnosed with ADHD and 8 with ASD. The participants' parents completed the Korean version of the Child Behavior Checklist (K-CBCL), the ADHD Rating Scale, and Conner's Scale at baseline and post-treatment. The participants completed the Korean Wechsler Intelligence Scale for Children-IV (K-WISC-IV) and the Advanced Test of Attention at baseline and the Penn Emotion Recognition and Discrimination Task at baseline and post-treatment. RESULTS: No significant changes in facial emotion recognition and discrimination occurred in either group before and after SST. However, when controlling for the processing speed of K-WISC and the social subscale of K-CBCL, the ADHD group showed more improvement in total (p=0.049), female (p=0.039), sad (p=0.002), mild (p=0.015), female extreme (p=0.005), male mild (p=0.038), and Caucasian (p=0.004) facial expressions than did the ASD group. CONCLUSION: SST improved facial expression recognition for children with ADHD more effectively than it did for children with ASD, in whom additional training to help emotion recognition and discrimination is needed.

Nutrient Intakes of Male College Combat Sport Athletes by Weight Control Status / 대한지역사회영양학회지

OBJECTIVES: Weight control practices are common in combat sport athletes. This study was performed to examine nutrient intakes of male college combat sport athletes (taekwondo, boxing, judo) by weight control (WC) status. METHODS: Subjects were male combat sport athletes (n=90) from colleges in Gyeonggi Province. Survey was conducted during 2016. Questionnaire included general characteristics, weight control, and dietary intakes during the period of training, weight control, weigh-in ~ before competition and between competitions. Subjects were grouped into high- and normal WC groups. T-test, χ²-test, Fisher's exact test and ANCOVA were used to analyze the data. RESULTS: During training, energy intake was 75.4% of EER and C:P:F ratio was 57.5:13.9:28.7. Iron and zinc intakes were different by WC groups (p<0.05). During weight control, energy intake was 44.7% of EER in normal WC and 30.5% in high WC group (p<0.05). C:P:F ratio was 69:11.1:19.5, and ratio from protein and fat was lower in the high WC group (p<0.05). Most nutrient intakes during weight control were less than 50% of 2015 KDRIs (RNI or AI), and intakes including thiamin (p<0.01), vitamin A, riboflavin, niacin, folate, calcium, potassium and zinc (p<0.05) were significantly lower in the high WC. Energy intake after weighing before the competition was 1,315 kcal, and energy (kcal/kg BW, p<0.05) and carbohydrate intakes (g/kg BW, p<0.01) were significantly higher in the high WC group. Energy intake between competitions was 691.1 kcal, with no difference by the WC group. CONCLUSIONS: Nutrients intakes of combat sport athletes were inadequate. Dietary intakes during weight control were much below than the KDRIs, especially in the high WC group. It is needed to develop nutrition education programs for combat sport athletes to avoid severe energy restrictions and to apply specific dietary guides to each period of training and weight control.

Development and Evaluation of Acellular Dermal Matrix Originated from Transgenic Porcine Skin for Primates Skin Graft

This study was performed to compare the healing quality of the allogenic acellular dermal matix (ADM) and xenogenic ADM combined with autologous split thicknessskin graft. Xenogenic ADM was obtained from two wild type pigs. Allogenic ADM was obtained from cynomolgus monkeys. ADM was stored with cryo-preservation. Full-thickness skin wounds were made on the back of two cynomolgus monkeys. In one monkey, wounds were covered by allogenic ADM combined with autologous split thickness skin graft (STSG) or autologous STSGonly. In another monkey, wounds were covered by xenogenic ADM combined with autologous skin graft or autologous skin graft only. Skin healing process was observed during 2 weeks and skin biopsies were performed on 3 months after skin transplantation. We obtained IACUC approval (ORIENT-IACUC-16053). Skin on the xenogenic ADM was necrotized 1 week after skin transplantation. Possibly due to the thickness of ADM, which block the blood supply from the subcutaneous tissue to the autologous skin graft. Skin biopsy revealed that less fibrotic change of the skin on the ADM compared with the skin without ADM. Xenogenic ADM can be used in high degree burn patients who can suffered from contracture after healing since it can reduce fibrotic change.

Difference of Facial Emotion Recognition and Discrimination between Children with Attention-Deficit Hyperactivity Disorder and Autism Spectrum Disorde

OBJECTIVES: This study aimed to investigate the differences in the facial emotion recognition and discrimination ability between children with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). METHODS: Fifty-three children aged 7 to 11 years participated in this study. Among them, 43 were diagnosed with ADHD and 10 with ASD. The parents of the participants completed the Korean version of the Child Behavior Checklist, ADHD Rating Scale and Conner's scale. The participants completed the Korean Wechsler Intelligence Scale for Children-fourth edition and Advanced Test of Attention (ATA), Penn Emotion Recognition Task and Penn Emotion Discrimination Task. The group differences in the facial emotion recognition and discrimination ability were analyzed by using analysis of covariance for the purpose of controlling the visual omission error index of ATA. RESULTS: The children with ADHD showed better recognition of happy and sad faces and less false positive neutral responses than those with ASD. Also, the children with ADHD recognized emotions better than those with ASD on female faces and in extreme facial expressions, but not on male faces or in mild facial expressions. We found no differences in the facial emotion discrimination between the children with ADHD and ASD. CONCLUSION: Our results suggest that children with ADHD recognize facial emotions better than children with ASD, but they still have deficits. Interventions which consider their different emotion recognition and discrimination abilities are needed.

Prevalence and Its Correlates of Night Eating Syndrome in Schizophrenic Outpatients / 정신신체의학

OBJECTIVES: The aim of study was to examine the prevalence of night eating syndrome(NES) and its correlates in schizophrenic outpatients. METHODS: The 14 items of self-reported night eating questionnaire(NEQ) was administered to 201 schizophrenic patients in psychiatric outpatient clinic. We examined demographic and clinical characteristics, body mass index(BMI), subjective measures of mood, sleep, binge eating, and weight-related quality of life using Beck's Depression Inventory(BDI), Pittsburgh Sleep Quality Index(PSQI), Binge Eating Scale(BES) and Korean version of Obesity-Related Quality of Life Scale(KOQoL), respectively. RESULTS: The prevalence of night eaters in schizophrenic outpatients was 10.4%(21 of 201). Comparisons between NES group and non-NES group revealed no significant differences in sociodemographic characteristics, clinical status and BMI. Compared to non-NES, patients with NES reported significantly greater depressed mood and sleep disturbance, more binge eating pattern, and decreased weight-related quality of life. While 'morning anorexia' and 'delayed morning meal'(2 of 5 NES core components in NEQ) were not differed between groups, 'nocturnal ingestions', 'evening hyperphagia', and 'mood/sleep' were more impaired in NES group. CONCLUSION: These findings are the first to describe the prevalence and its correlates of night eaters in schizophrenic outpatients. These results suggest that NES has negative mental health implications, although it was not associated with obesity. Further study to generalize these results is required.

Prevalence and Its Correlates of Restless Legs Syndrome in Outpatients with Bipolar Disorders / 정신신체의학

OBJECTIVES: This study was to assess the prevalence and its correlates of restless legs syndrome(RLS) in outpatients with bipolar disorder. METHODS: A total of 100 clinical stabilized bipolar outpatients were examined. The presence of RLS and its severity were assessed using the International Restless Legs Sydrome Study Group(IRLSSG) diagnostic criteria. Beck's Depression Inventory(BDI), Spielberg's State Anxiety Inventory(STAI-X-1), Pittsburgh Sleep Quality Index(PSQI), Korean version Drug Attitude Inventory(KDAI-10), Subjective Well-Beings under Neuroleptic Treatment Scale-Short Form(SWN-K) and Barnes Akathisia Rating Scale(BARS) were used to evaluate the depressive symptomatology, level of anxiety, subjective quality of sleep, subjective feeling of well-being, drug attitude, presence of akathisia, respectively. RESULTS: Of the 100 bipolar outpatients, 7(7%) were met to full criteria of IRLSSG and 36(36%) have at least one of the 4 IRLSSG criterion. Because of relatively small sample size, non-parametric analysis were done to compare the characteristics among 3 groups(full-RLS, 1> or =positive RLS-symptom and Non-RLS). There were no significant differences in sex, age, and other sociodemographic and clinical data among 3 groups. BDI, STAI-X-1 and PSQI are tended to be impaired in RLS and 1> or =positive RLS-symptom groups. CONCLUSIONS: This is the first preliminary study for studying the prevalence and its correlates of RLS in bipolar disorder. The results shows that relatively small proportion of RLS was present in bipolar disorder patients when compared to patients with schizophrenia. Same tendencies shown in schizophrenic patients were found that bipolar patients with RLS had more depressive symptoms, state anxiety and poor subjective sleep quality. Further systematic studies may be needed to find the characteristics of RLS in bipolar patients.

Identification and Functional Characterization of P159L Mutation in HNF1B in a Family with Maturity-Onset Diabetes of the Young 5 (MODY5)

Mutation in HNF1B, the hepatocyte nuclear factor-1beta (HNF-1beta) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-1beta in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic beta-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in beta-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

The Effect of Weight Reduction on the Obesity-Related Quality of Life, Physical and Emotional Well-Being in Obese Schizophrenic Inpatients / 대한정신약물학회지

OBJECTIVE: The purpose of this study was to assess the effect of the weight reduction program designed for schizophrenic patients. It's effects were assessed especially in the aspects of the obesity-related quality of life, emotional and physical well-being of the patients. METHODS: Fifty-one obese schizophrenic inpatients were enrolled in a 12-week, randomized weight reduction program. Thirty-two patients were randomly assigned to an intervention group in which they received the weight management program. Nineteen patients were allocated to the control group in which they received the usual clinical inpatient treatments. Body weight, Body Mass Index (BMI) and Quality of Life Scales such as Short Form of Medical Outcome Study (SF-36), Korean version of Obesity-related Quality of Life Scale (KOQOL) and Korean version of Body Weight, Image and Self-Esteem Evaluation Questionnaire (B-WISE-K) were evaluated during 12-week period. All assessments were done at baseline, 4, 8 and 12 week. Repeated measures of analysis of variance and post-hoc comparisons were done to compare the group differences from baseline at each visit. RESULTS: Sixteen of 32 (50%) patients in intervention group and 12 of 19 (69.4%) patients in control group completed this study. We found significant group by time interaction effects in weight, BMI and waist circumferences (p<0.05, respectively). The weight changes from baseline to 8 week and 12 week were significant in post-hoc comparisons between intervention and control groups (p<0.05 and p<0.01, respectively). The changes of BMI and waist circumference from baseline to 12-week were also significant in post-hoc comparisons (p<0.05). After completion of the weight management program, there were significant differences on the subjective estimates such as physical component summary of SF-36, and total scores, psychosocial heath, physical health and diet of the KOQOL, and total scores of B-WISE-K between intervention and control group. These significant differences were found at 12-week of treatment in post-hoc comparisons (p<0.05, respectively). CONCLUSION: The weight reduction program was effective for weight loss in schizophrenic inpatients. In addition, it might improve the subjective estimates such as obesity-related quality of life and weight-related body image in schizophrenic inpatients.

Lectins Isolated from Mushroom Fomitella fraxinea Enhance MHC-restricted Exogenous Antigen Presentation

BACKGROUND: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). METHODS: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. RESULTS: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-2K(b)) and class II (I-A(b)) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. CONCLUSION: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

Clinical Analysis Of Iga Nephropathy In Patients Over 50 Years Of Age / 대한내과학회지

BACKGROUND: IgA nephropathy is recognized as a disease affecting primarily young men under 30 years of age but it is relatively uncommon over 50 years of age. Findings on clinical and histological presentation and outcome of over 50 years of age have rarely published in Korea. METHODS: Between Febrary 1994 and July 2003, one hundred and thirty nine IgAN patients were recruited over 8 years. Nineteen patients over age 50 were compared to one hundred and twenty patients under age 50 clinical, histological findings, 5-Yr renal survival rate. Mean post-biopsy follow-up month was 23.8 +/- 23.5 months. RESULTS: Both group of patients were similar to baseline for gross hematuria, Male and female ratio. But older patients had a higher incidence of daily for 24 hour urine protein (p=0.010), systolic and diastolic blood pressure (p=0.010, p<0.01), serum C3 (p=0.001) and serum C4 (p=0.003). Albumin (p=0.011), creatinine clearance (p<0.01) were significantly lower in the older patients at the time of renal biopsy. Histologic grade IV was more common in the older patients (p=0.001). Moderate to severe mesangial proliferation (p=0.001) and crescent formation (p=0.043), arteriolosclerosis (p=0.006) were more common in older patients. Mesangial small deposition of IgA (p=0.007) and glomerular peripheral deposition of IgG, IgA, C1q (p=0.024, p=0.014, p=0.009) were more common in older patients than in under 50 years of age. Mesangial small electron dense deposits were more common in older patients than in younger patients (p=0.031). CRF (Ccr < 60 mL/min) was confirmed 55.6% over age 50 and 27.4% under age 50 (p=0.017). Renal replacement therapy was done 15.8% over age 50 and 4.3% under age 50 (p=0.048). 5-Year renal survival curves showed that kidney survival rate was 44.4% over age 50 and 72.6% under age 50 (p=0.0248). CONCLUSION: Poor prognostic factors were more common over age 50 than under age 50. CRF and renal replacement therapy were more common over age 50. Analysis of renal survival curves shows that the probability of developing ESRF increase after age 50. But, prolonged prospective follow-up is necessary to confirm this trend.

A case of minimal change nephropathy with malignant thymoma / 대한내과학회지

It is the first case that nephrotic syndrome with malignant thymoma reported in Korea. A 56-year-old man have had generalized edema, weight gain, dyspnea, oliguria for 10 days. At that time, a full blown nephrotic syndrome developed, with minimal change glomerulopathy, A mediastinum mass was shown by the chest X-ray. Thymectomy and palliative radiotherapy was done. In the treatment of nephrotic syndrome, firstly diuretics and prednisolone were given. but the response was poor, so additionally cyclophosphamide and azathioprine were given. After 1 year passed, the patient died of the respiratory failure with pulmonary fibrosis of complication of radiotherapy, without improvement in nephrotic syndrome.