Epidemiology of Childhood Obesity in Korea

Ha, Kyoung Hwa,Kim, Dae Jung Korean Endocrine Society 2016 Endocrinology and metabolism Vol.31 No.4

<P>Over the past several decades, the prevalence of obesity has increased dramatically worldwide and is increasing not only in developed countries, but also in developing countries. This increase may lead to an increase in the incidence of chronic diseases throughout the lifespan. In Korean children and adolescents, the prevalence of obesity increased from 6.8% in 1998 to 10.0% in 2013. Obesity is a state that more commonly influences children and adolescents of lower socioeconomic status (SES) than those with a higher SES. However, the prevalence of metabolic syndrome in a nationally representative sample of Korean adolescents decreased from 1998 to 2012. According to the Diabetes Fact Sheet of the Korean Diabetes Association, the prevalence of type 2 diabetes among children aged 18 years or younger was 153.5 per 100,000 in 2006 and 205.0 per 100,000 in 2013. Obesity is a complex disease influenced by many interacting factors, such as adipocytokines, lipopolysaccharide-binding protein, adenovirus 36 infection, birth weight, lifestyle, and endocrine-disrupting chemicals. Obesity in youth can adversely impact practically every organ system and lead to serious consequences, such as metabolic, gastrointestinal, pulmonary, cardiovascular, and psychosocial complications. Therefore, coordinated efforts by governments, organizations, communities, and individuals are needed to prevent and treat childhood obesity. In particular, a long-term policy to improve the social environment will also be necessary.</P>

Prevalence and Characteristics of Metabolically Obese but Normal Weight and Metabolically Healthy but Obese in Middle-aged Koreans: the Chungju Metabolic Disease Cohort (CMC) Study

Lee, Seung-Hwan,Ha, Hee-Sung,Park, Young-Jun,Lee, Jin-Hee,Yim, Hyeon-Woo,Yoon, Kun-Ho,Kang, Moo-Il,Lee, Won-Chul,Son, Ho-Young,Park, Yong-Moon,Kwon, Hyuk-Sang Korean Endocrine Society 2011 Endocrinology and metabolism Vol.26 No.2

Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective

Sohn, Seo Young,Jang, Hye Won,Cho, Yoon Young,Kim, Sun Wook,Chung, Jae Hoon Korean Endocrine Society 2015 Endocrinology and metabolism Vol.30 No.4

<P><B>Background</B></P><P>Previous studies have suggested that recombinant human thyroid stimulating hormone (rhTSH) stimulation is an acceptable alternative to thyroid hormone withdrawal (THW) when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective.</P><P><B>Methods</B></P><P>This economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY) associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets.</P><P><B>Results</B></P><P>The additional benefits of rhTSH (0.036 QALY) are achieved with an additional cost of Korean won ₩961,105, equating to cost per QALY of ₩26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately ₩33,000,000/QALY.</P><P><B>Conclusion</B></P><P>The use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea.</P>

1,5-Anhydro-D-Glucitol Could Reflect Hypoglycemia Risk in Patients with Type 2 Diabetes Receiving Insulin Therapy

Kim, Min Kyeong,Jung, Hye Seung,Kwak, Soo Heon,Cho, Young Min,Park, Kyong Soo,Kim, Seong Yeon Korean Endocrine Society 2016 Endocrinology and metabolism Vol.31 No.2

<P><B>Background</B></P><P>The identification of a marker for hypoglycemia could help patients achieve strict glucose control with a lower risk of hypoglycemia. 1,5-Anhydro-D-glucitol (1,5-AG) reflects postprandial hyperglycemia in patients with well-controlled diabetes, which contributes to glycemic variability. Because glycemic variability is related to hypoglycemia, we aimed to evaluate the value of 1,5-AG as a marker of hypoglycemia.</P><P><B>Methods</B></P><P>We enrolled 18 adults with type 2 diabetes mellitus (T2DM) receiving insulin therapy and assessed the occurrence of hypoglycemia within a 3-month period. We measured 1,5-AG level, performed a survey to score the severity of hypoglycemia, and applied a continuous glucose monitoring system (CGMS).</P><P><B>Results</B></P><P>1,5-AG was significantly lower in the high hypoglycemia-score group compared to the low-score group. Additionally, the duration of insulin treatment was significantly longer in the high-score group. Subsequent analyses were adjusted by the duration of insulin treatment and mean blood glucose, which was closely associated with both 1,5-AG level and hypoglycemia risk. In adjusted correlation analyses, 1,5-AG was negatively correlated with hypoglycemia score, area under the curve at 80 mg/dL, and low blood glucose index during CGMS (<I>P</I>=0.068, <I>P</I>=0.033, and <I>P</I>=0.060, respectively).</P><P><B>Conclusion</B></P><P>1,5-AG level was negatively associated with hypoglycemia score determined by recall and with documented hypoglycemia after adjusting for mean glucose and duration of insulin treatment. As a result, this level could be a marker of the risk of hypoglycemia in patients with well-controlled T2DM receiving insulin therapy.</P>

The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women

Kim, Hyeonmok,Ahn, Seong Hee,Shin, Chaeho,Lee, Seung Hun,Kim, Beom-Jun,Koh, Jung-Min Korean Endocrine Society 2016 Endocrinology and metabolism Vol.31 No.3

<P><B>Background</B></P><P>Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women.</P><P><B>Methods</B></P><P>A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria.</P><P><B>Results</B></P><P>Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (<I>P</I>=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73).</P><P><B>Conclusion</B></P><P>This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.</P>

Determination of Mother Centriole Maturation in CPAP-Depleted Cells Using the Ninein Antibody

Lee, Miseon,Rhee, Kunsoo Korean Endocrine Society 2015 Endocrinology and metabolism Vol.30 No.1

<P><B>Background</B></P><P>Mutations in centrosomal protein genes have been identified in a number of genetic diseases in brain development, including microcephaly. Centrosomal P4.1-associated protein (CPAP) is one of the causal genes implicated in primary microcephaly. We previously proposed that CPAP is essential for mother centriole maturation during mitosis.</P><P><B>Methods</B></P><P>We immunostained CPAP-depleted cells using the ninein antibody, which selectively detects subdistal appendages in mature mother centrioles.</P><P><B>Results</B></P><P>Ninein signals were significantly impaired in CPAP-depleted cells.</P><P><B>Conclusion</B></P><P>The results suggest that CPAP is required for mother centriole maturation in mammalian cells. The selective absence of centriolar appendages in young mother centrioles may be responsible for asymmetric spindle pole formation in CPAP-depleted cells.</P>

Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse β-Cells

Kim, Min Joo,Choi, Ok Kyong,Chae, Kyung Sil,Kim, Min Kyeong,Kim, Jung Hee,Komatsu, Masaaki,Tanaka, Keiji,Lee, Hakmo,Chung, Sung Soo,Kwak, Soo Heon,Cho, Young Min,Park, Kyong Soo,Jung, Hye Seung Korean Endocrine Society 2015 Endocrinology and metabolism Vol.30 No.1

<P><B>Background</B></P><P>Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (<I>Atg7</I>)-deficient β-cells.</P><P><B>Methods</B></P><P>To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from <I>Atg7</I><SUP>F/F</SUP>:RIP-<I>Cre</I>+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in <I>Atg7</I>-deficient islets and in β-TC6 cells transfected with si<I>Atg7</I> was measured by quantitative real-time polymerase chain reaction.</P><P><B>Results</B></P><P>Baseline oxygen consumption rate of <I>Atg7</I>-deficient islets was significantly lower than that of control islets (<I>P</I><0.05). Intracellular ATP content of <I>Atg7</I>-deficient islets during glucose stimulation was also significantly lower than that of control islets (<I>P</I><0.05). By Oxygraph-2k analysis, mitochondrial respiration in <I>Atg7</I>-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in <I>Atg7</I>-deficient islets were significantly lower than in control islets (<I>P</I><0.05). Down-regulation of <I>Atg7</I> in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (<I>P</I><0.1).</P><P><B>Conclusion</B></P><P>Impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.</P>

Functional Identification of Compound Heterozygous Mutations in the <i>CYP17A1</i> Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency

Mo, Eun Yeong,Lee, Ji-young,Kim, Su Yeon,Kim, Min Ji,Kim, Eun Sook,Lee, Seungok,Han, Je Ho,Moon, Sung-dae Korean Endocrine Society 2018 Endocrinology and metabolism Vol.33 No.3

<P><B>Background</B></P><P>We previously reported a patient with congenital adrenal hyperplasia (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (<I>CYP17A1</I>) gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation. The aim of this study was to investigate the functional properties of a new allele present in a compound heterozygote of <I>CYP17A1</I>.</P><P><B>Methods</B></P><P>To understand how p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and mutant <I>CYP17A1</I> cDNAs were cloned into flag-tagged pcDNA3 vector and introduced into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels of CYP17A1 were then analyzed. And the activities of 17α-hydroxylase and 17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone to 17α-hydroxyprogesterone and of 17α-hydroxypregnenolone to dehydroepiandrosterone, respectively. In addition a computer model was used to create the three-dimensional structure of the mutant CYP17A1 enzymes.</P><P><B>Results</B></P><P>Production of the p.His373Leu mutant protein was significantly lower than that of the wild type protein, and the p.Glu383fsX36 protein was hardly produced. Similarly the enzymatic activity derived from the p.His373Leu mutant vector was significantly lower than that obtained from the wild type vector, and little activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling of the enzyme showed that p.His373 was located in region important for heme-binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant protein formed a heme-binding structure.</P><P><B>Conclusion</B></P><P>Enzyme activity measured in both mutants disappeared completely in both 17α-hydroxylase and 17,20-lyase. This result accounts for the clinical manifestations of the patient with the compound heterozygous <I>CYP17A1</I> mutations.</P>

Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

Yoon, Ye Ran,Baik, Ja-Hyun Korean Endocrine Society 2015 Endocrinology and metabolism Vol.30 No.4

<P><B>Background</B></P><P>The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards.</P><P><B>Methods</B></P><P>We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene.</P><P><B>Results</B></P><P>In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward.</P><P><B>Conclusion</B></P><P>We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors.</P>

Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-α-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes

Hong, Seok-Woo,Lee, Jinmi,Park, Se Eun,Rhee, Eun-Jung,Park, Cheol-Young,Oh, Ki-Won,Park, Sung-Woo,Lee, Won-Young Korean Endocrine Society 2014 Endocrinology and metabolism Vol.29 No.4

<P><B>Background</B></P><P>Tumor necrosis factor (TNF)-α and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated.</P><P><B>Methods</B></P><P>The key factors and mechanism of action of TNF-α and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 α (eIF2α) by Western blot and an immunofluorescence assay in 24-hour TNF-α-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation.</P><P><B>Results</B></P><P>Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-α-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-α and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2α, a component of the unfolded protein response signaling pathway, was observed in TNF-α or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-α-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2α.</P><P><B>Conclusion</B></P><P>These data indicated that AICAR-induced AMPK activation attenuates TNF-α-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2α activity is a novel mechanism of the anti-lipolytic effect of AICAR.</P>