Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation

Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells’ point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation.

The Relationships between Addiction to Highly Caffeinated Drinks, Burnout, and Attention-Deficit/Hyperactivity Disorder

OBJECTIVES: This study aimed to evaluate the addiction to highly caffeinated drinks among university students, and we investigated the relationships between smartphone addiction, depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), burnout, self-esteem, impulsiveness in high caffeine drink addiction risk group (high caffeine group). We also compared these mental health factors differences between the high caffeine group and the control group; and, investigated the relative risk between the independent variables of the high caffeine group. METHODS: This study was conducted in Korea, from June 2015 to July 2016. A set of questionnaires was administered on 511 college students. RESULTS: The participants who belonged to the high caffeine group were more likely to demonstrate the symptoms of ADHD and higher levels of burnout and impulsiveness. Further, the results of logistic regression analysis confirmed the association between the high caffeine group and burnout. CONCLUSION: These behaviors among university students addicted to highly caffeinated drinks suggests the need for timely and effective interventions for those at risk of addiction.

Efficacy of evogliptin and cenicriviroc against nonalcoholic steatohepatitis in mice: a comparative study

Dipeptidyl peptidase (DPP)-4 inhibitors, or gliptins, are a class of oral hypoglycemic drugs that have been widely used as a second-line treatment for type 2 diabetes. Gliptins, which were introduced for clinical use a decade ago, have been shown to be beneficial against nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) in animals and humans. Cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor type 2 and 5, is currently under investigation against NASH and fibrosis. It was previously discovered that evogliptin (EVO) reduces hepatic steatosis in diet-induced obese animals but the effectiveness of EVO on NASH remains unexplored. Here, we compared the effectiveness of EVO and CVC against NASH and fibrosis in mice fed a high-fat and high-fructose diet (HFHF). Biochemical and histological analyses showed that mice fed a HFHF for 20 weeks developed severe hepatic steatosis and inflammation with mild fibrosis. Administration of EVO (0.2% wt/wt) for the last 8 weeks of HFHF feeding significantly reduced hepatic triglyceride accumulation, inflammation, and fibrosis as well as restored insulin sensitivity, as evidenced by lowered plasma insulin levels and the improvement in insulin tolerance test curves. Treatment of mice with CVC (0.1% wt/wt) inhibited hepatic inflammation and fibrogenesis with similar efficacy to that of EVO, without affecting hepatic steatosis. CVC treatment also reduced plasma insulin concentrations, despite no improvement in insulin tolerance. In conclusion, EVO administration efficiently ameliorated the development of NASH and fibrosis in HFHF-fed mice, corroborating its therapeutic potential.

Rhodanthpyrone A and B play an anti-inflammatory role by suppressing the nuclear factor-κB pathway in macrophages

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor (NF)-κB pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an NF-κB inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the NF-κB pathway during macrophage-mediated inflammation.

A diagnosis of hypochondroplasia by next generation sequencing

Achondroplasia and hypochondroplasia are the two most common forms of short-limb dwarfism. They are autosomal dominant diseases that are characterized by a rhizomelic shortening of the limbs, large head with frontal bossing, hypoplasia of the mid-face, genu varum and trident hands. Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene, which is located on chromosome 4p16.3, have been reported to cause achondroplasia and hypochondroplasia. More than 98% of achondroplasia cases are caused by the G380R mutation (c.1138G>A or c.1138G>C). In contrast, the N540K mutation (c.1620C>A) is detected in 60-65% of hypochondroplasia cases. Tests for common mutations are often unable to detect the mutation in patients with a clinical diagnosis of hypochondroplasia. In this study, we presented a case of familial hypochondroplasia with a rare mutation in FGFR3 identified by next generation sequencing.

The corrected QT (QTc) prolongation in hyperthyroidism and the association of thyroid hormone with the QTc interval / 소아과

PURPOSE: Ventricular repolarization is assessed using the QT interval corrected by the heart rate (QTc) via an electrocardiogram (ECG). Prolonged QTc is associated with an increased risk of arrhythmias and cardiac mortality. As there have been few reports regarding the effects of hyperthyroidism on ventricular repolarization, we studied the association between serum free thyroxine (free T4 [fT4]) and thyroid stimulating hormone (TSH) levels and the QTc interval. METHODS: Thirty-eight patients with hyperthyroidism (<30 years old) were included, and we used their clinical records and available ECGs (between August 2003 and August 2011) to evaluate the association between their fT4 and TSH levels and their QTc interval. In addition, we studied the ECGs of 72 age-matched patients with no hyperthyroidism (control group) and compared their data with that from the patients group. RESULTS: The QTc duration in patients with hyperthyroidism was significantly prolonged compared to that in the control subjects (P<0.001). In addition, the number of hyperthyroid patients with abnormal prolonged QTc was significantly higher than that in the control group (P<0.001). Among the patients with hyperthyroidism, patients with prolonged QTc and borderline QTc had higher fT4 levels and there was positive correlation between their fT4 levels and their QTc interval (P<0.05). However, no correlation was observed between their TSH levels and their QTc interval. CONCLUSION: We report that hyperthyroidism is associated with QTc prolongation. The correlation between the fT4 levels and the QTc interval suggests that thyroid status is associated with QTc values and the risk of cardiac mortality.

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia / 소아과

Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 (p.Gln213*). To our knowledge, this is a novel mutation in GNAS.

Changes in longitudinal craniofacial growth in subjects with normal occlusions using the Ricketts analysis / 대한치과교정학회지

OBJECTIVE: This study was designed to define the Korean norm values for the Ricketts analysis. METHODS: In this longitudinal study, lateral cephalograms of 31 subjects with normal occlusion were taken biennially from ages 9-19 years. Cephalometric measurements were performed. Parameters for which the 10-year change did not exceed one standard deviation were defined as unchanged. The means and standard deviations for the measured parameters were determined for each age group. RESULTS: No significant changes in growth were observed in the molar relationship, incisor overjet, incisor overbite, mandibular incisor extrusion, interincisor angle, lower incisor tip (B1) to A point-Pogonion (A-PO) plane, upper incisor tip (A1) to A-PO plane, B1 inclination to A-PO, A1 inclination to A-PO, B1 inclination to Frankfurt plane (FH), convexity, lower facial height, facial axis, maxillary depth, maxillary height, palatal plane to FH, cranial deflection, ramus Xi position, or porion location. Continual changes over the 10 years of growth were observed in the maxillary first molar distal position to pterygoid true vertical plane, facial depth, mandibular plane to FH, anterior cranial length, mandibular arc, and corpus length. CONCLUSIONS: Clinicians can apply the Korean norms at age 9 as determined in this study when using the Ricketts analysis. The patient's age at the beginning of treatment and their sex should be taken into consideration when drawing visual treatment objectives.

A Clinical Study of the Relationship between Obesity and Pubertal Development in Girls / 대한소아소화기영양학회지

PURPOSE: Recently, public interest in obesity and earlier pubertal development has been increasing. The purpose of this study was to analyze the relationship between obesity and pubertal development in girls. METHODS: A total of 158 girls presenting with earlier pubertal development from July 2008 to June 2010 were included in the study. Their mean age was 8.27+/-1.3 years and the mean bone age advancement was 1.86+/-0.3 years. RESULTS: Based on weight-for-height percentiles, their obesity rate was 9.2% and overweight rate was 15.8%. However, for body mass index (BMI), the result was a bit different; with an obesity rate of 13.2% and overweight rate of 24.3%. About 40% of the girls had a family history of early maturation. Among them, 25.7% had a maternal history, 4.6% paternal and 7.2% both. However, 60% of them had no family history. We then classified these girls into families with one son and one daughter, and those with two daughters. In one-son/one-daughter families, 69.3% were the first children and 30.7% were second. In two-daughter families, 65.3% were the first and 34.7% were second. We found that 67.5% had a history of taking herbal medicine. CONCLUSION: The obesity and overweight rates in girls with earlier pubertal development were higher than those of normal girls, but with a small discrepancy between weight-for-height percentile and BMI-based results. Furthermore, taking herbal medicine seems to be a potential factor for earlier pubertal development in Korea.

Hutchinson-Gilford Progeria Syndrome with G608G LMNA Mutation

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition originally described by Hutchinson in 1886. Death result from cardiac complications in the majority of cases and usually occurs at average age of thirteen years. A 4-yr old boy had typical clinical findings such as short stature, craniofacial disproportion, alopecia, prominent scalp veins and sclerodermatous skin. This abnormal appearance began at age of 1 yr. On serological and hormonal evaluation, all values are within normal range. He was neurologically intact with motor and mental development. An echocardiogram showed calcification of aortic and mitral valves. Hypertrophy of internal layer at internal carotid artery suggesting atherosclerosis was found by carotid doppler sonography. He is on low dose aspirin to prevent thromboembolic episodes and on regular follow up. Gene study showed typical G608G (GGC- > GGT) point mutation at exon 11 in LMNA gene. This is a rare case of Hutchinson-Gilford progeria syndrome confirmed by genetic analysis in Korea.