Young Jun Rhie

Effects of body composition, leptin, and adiponectin on bone mineral density in prepubertal girls.

Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism.

Integrative Physiology: Defined Novel Metabolic Roles of Osteocalcin

The prevailing model of osteology is that bones constantly undergo a remodeling process, and that the differentiation and functions of osteoblasts are partially regulated by leptin through different central hypothalamic pathways. The finding that bone remodeling is regulated by leptin suggested possible endocrinal effects of bones on energy metabolism. Recently, a reciprocal relationship between bones and energy metabolism was determined whereby leptin influences osteoblast functions and, in turn, the osteoblast-derived protein osteocalcin influences energy metabolism. The metabolic effects of bones are caused by the release of osteocalcin into the circulation in an uncarboxylated form due to incomplete γ-carboxylation. In this regard, the Esp gene encoding osteotesticular protein tyrosine phosphatase is particularly interesting because it may regulate γ-carboxylation of osteocalcin. Novel metabolic roles of osteocalcin have been identified, including increased insulin secretion and sensitivity, increased energy expenditure, fat mass reduction, and mitochondrial proliferation and functional enhancement. To date, only a positive correlation between osteocalcin and energy metabolism in humans has been detected, leaving causal effects unresolved. Further research topics include: identification of the osteocalcin receptor; the nature of osteocalcin regulation in other pathways regulating metabolism; crosstalk between nutrition, osteocalcin, and energy metabolism; and potential applications in the treatment of metabolic diseases.

Effects of a structured exercise program on insulin resistance, inflammatory markers and physical fitness in obese Korean children.

ABSTRACT Thirty-eight obese Korean children (21 boys, 17 girls), whose ages were between 9 and 15, were divided into either the intervention group (19 obese children: BMI>95P) or the age- and sex-matched obese control group. The intervention group performed an intensive exercise program under the supervision of educated instructors for 12 weeks (90 minutes/day, two days/week) and received lifestyle modification counseling using food diaries and phone calls. The control group participated in conventional counseling at an out-patient clinic. The intervention group appeared to have more improvement of body weight, body composition, serum lipid profiles and high-sensitivity C-reactive protein (hs-CRP) levels (P < 0.05) but without changes in serum adiponectin level. HOMA-IR decreased from 2.3 to 1.3 in the intervention group. Maximal oxygen consumption (VO2 max) and other physical fitness parameters were significantly improved after the intervention program (P < 0.05).

Serum Kisspeptin Levels in Korean Girls with Central Precocious Puberty

Central precocious puberty (CPP) is caused by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G-protein coupled receptor-54 system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. We aimed to determine whether serum kisspeptin may function as a marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with a competitive enzyme immunoassay. Serum kisspeptin levels were significantly higher in CPP group than in control group (4.61 ± 1.78 vs 2.15 ± 1.52 pM/L, P < 0.001). Serum kisspeptin was positively correlated with peak luteinizing hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by premature increase of kisspeptin. Serum kisspeptin may be used as a marker of CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of premature increase of kisspeptin and upstream regulator of kisspeptin are also needed.

Association of serum retinol binding protein 4 with adiposity and pubertal development in Korean children and adolescents.

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.

Can early B-type natriuretic peptide assays predict symptomatic patent ductus arteriosus in extremely low birth weight infants?

Background: Earlier and more accurate identification of a high-risk group of preterm infants that are likely to develop a hemodynamically significant patent ductus arteriosus (hsPDA) would allow specific targeting of early treatment and thus possibly minimize the morbidity and mortality associated with a PDA in extremely low birth weight (ELBW) infants. Objective: To investigate the predictability of B-type natriuretic peptide (BNP) for early targeted treatment of hsPDA in ELBW infants. Methods: 73 ELBW infants that underwent echocardiographic evaluation and plasma BNP measurement after birth were enrolled. 31 infants developed hsPDA (HsPDA group) and 42 infants did not develop hsPDA (nPDA group). Results: BNP levels of the HsPDA group were significantly higher than those of the nPDA group at 24 h of age (921 [318–2,133] vs. 152 [91–450] pg/ml) but not different at 12 h of age. BNP levels at 24 h of age were significantly correlated with the magnitudes of the ductal shunt but not at 12 h of age. The area under the receiver operator characteristic curve of BNP levels for prediction of hsPDA at 24 h of age was 0.830. At the cutoff BNP levels of 200 and 900 pg/ml at 24 h of age, sensitivity was 83.9 and 54.8% and specificity was 61.9 and 95.2%, respectively. Conclusions: BNP levels at 24 h of age can be used as a guide for early targeted treatment of hsPDA and avoid the unnecessary use of cyclooxygenase inhibitors in ELBW infants.

Influence of Bottle-Feeding on Serum Bisphenol A Levels in Infants

Exposure to endocrine disrupting chemicals (EDCs), particularly during developmental periods, gives rise to a variety of adverse health outcomes. Bisphenol A (BPA) is a well-known EDC commonly found in plastic products including food and water containers, baby bottles, and metal can linings. This study investigates infant exposure to BPA and the effect of bottle-feeding on serum BPA levels in infants. Serum BPA levels in normal healthy infants 6 to 15 months of age (n=60) were evaluated by a competitive ELISA. BPA was detected in every study sample. Serum BPA levels of bottle-fed infants (n=30) were significantly higher than those of breast-fed infants (n=30) (96.58±102.36 vs 45.53±34.05 pg/mL, P=0.014). There were no significant differences in serum BPA levels between boys (n=31) and girls (n=29). No significant correlations were found between serum BPA levels and age, body weight, birth weight, and gestational age. Bottle-feeding seems to increase the risk of infant exposure to BPA. Establishment of health policies to reduce or prevent BPA exposure in infants is necessary. Graphical Abstract

Age of menarche and near adult height after long-term gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty.

Purpose Gonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa. Methods In this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height using the Bayley-Pinneau method and identified the age of menarche in girls with CPP. Results Mean chronological and bone age at menarche were 11.9±0.7 and 12.8±0.4 years, respectively. The period between menarche and the end of treatment was 14.0±5.6 months. Posttreatment near adult height was 163.8±4.7 cm, which was significantly greater than pretreatment predicted adult height (158.7±4.1 cm). Conclusion GnRHa treatment in girls with CPP could improve final adult height and made the age of menarche close to that of the general population.

Kisspeptin/G protein-coupled receptor-54 system as an essential gatekeeper of pubertal development.

Puberty is the end-point of a complex series of developmental events, defined by the dynamic interaction between genetic factors and environmental cues, ultimately leading to the attainment of reproductive capacity. Kisspeptins, products of the KISS1 gene, were originally identified as metastasis suppressor peptides with the ability to bind G protein-coupled receptors (GPR54). In 2003, loss-of-function mutations of the GPR54 gene were found in patients with hypogonadotropic hypogonadism. This finding triggered study of the role of the kisspeptin/GPR54 system as an essential gatekeeper of control of reproduction and pubertal development. Kisspeptins are very potent elicitors of gonadotropin secretion, primarily through stimulation of gonadotropin-releasing hormone release. KISS1 also functions as an essential integrator for peripheral inputs, including gonadal steroids and nutritional signals, and for controlling GnRH and gonadotropin secretion. Whether the kisspeptin/GPR54 system is the trigger for puberty onset and/or it operates as integrator and effector of up-stream regulatory factors warrants further investigation.

Factors to Predict Positive Results of Gonadotropin Releasing Hormone Stimulation Test in Girls with Suspected Precocious Puberty

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.