ASAYAMA, KOHTARO, HIDEMASA HAYASHIBE, KAZUSHIGE DOBASHI, NORIHIKO UCHIDA, TAKAYA NAKANE, KOHJI KODERA, AKIRA SHIRAHATA, AND MATSUO TANIYAMA. Decrease in serum adiponectin level due to obesity and visceral fat accumulation in children. Obes Res. 2003;11:1072-1079. Objective: To determine whether serum adiponectin is decreased in obesity and is restored toward normal level after treatment in children. Research Methods and Procedures: Subjects were 53 Japanese obese children, 33 boys and 20 girls (6 to 14 years old), and 30 age-matched nonobese controls for measuring adiponectin (16 boys and 14 girls). Blood was drawn after an overnight fast, and the obese children were subjected to anthropometric measurements including waist and hip circumferences and skinfold thicknesses. Paired samples were obtained from 21 obese children who underwent psychoeducational therapy. Visceral adipose tissue area was measured by computed tomography. Adiponectin was assayed by an enzyme-linked immunosorbent assay. Results: The serum levels of alanine aminotransferase, uric acid, triglyceride, total cholesterol, low-density lipoproteincholesterol, total cholesterol/high-density lipoprotein-cholesterol, apo B, apo B/apo A 1 , and insulin in obese children were higher than the reference values. Serum adiponectin level was lower in the obese children than in the controls (6.4 Ϯ 0.6 vs. 10.2 Ϯ 0.8 mg/L, means Ϯ SEM, p Ͻ 0.001). In 21 obese children whose percent overweight declined during therapy, the adiponectin level increased (p ϭ 0.002). The adiponectin level was correlated inversely with visceral adipose tissue area in obese children (r ϭ Ϫ0.531, p Ͻ 0.001). The inverse correlations of adiponectin with alanine aminotransferase, uric acid, and insulin were significant after being adjusted for percentage overweight, percentage body fat, or sex. Discussion: Serum adiponectin level is decreased in obese children depending on the accumulation of visceral fat and is restored toward normal level by slimming.

Transcription factors operate in developmental processes to mediate inductive events and cell competence, and perturbation of their function or regulation can dramatically affect morphogenesis, organogenesis, and growth. We report that a narrow spectrum of amino-acid substitutions within the transactivation domain of the v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a leucine zipper-containing transcription factor of the AP1 superfamily, profoundly affect development. Seven different de novo missense mutations involving conserved residues of the four GSK3 phosphorylation motifs were identified in eight unrelated individuals. The distinctive clinical phenotype, for which we propose the eponym Aymé-Gripp syndrome, is not limited to lens and eye defects as previously reported for MAF/Maf loss of function but includes sensorineural deafness, intellectual disability, seizures, brachycephaly, distinctive flat facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced growth. Disease-causing mutations were demonstrated to impair proper MAF phosphorylation, ubiquitination and proteasomal degradation, perturbed gene expression in primary skin fibroblasts, and induced neurodevelopmental defects in an in vivo model. Our findings nosologically and clinically delineate a previously poorly understood recognizable multisystem disorder, provide evidence for MAF governing a wider range of developmental programs than previously appreciated, and describe a novel instance of protein dosage effect severely perturbing development.

OBJECTIVE:To determine whether the direct measure of visceral adipose tissue (VAT) by computed tomography (CT) is a superior diagnostic criterion to the anthropometric surrogates and more classical criteria of obesity. DESIGN: Cross-sectional, clinical study. Obese boys were classified according to the occurrence of abnormal values in either serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion for such metabolic derangement was calculated, using the analysis of receiver operating characteristic (ROC) curve. SUBJECTS: Seventy-five consecutive outpatient Japanese obese boys, ranging in age from 6 to 14 y, were studied. MEASUREMENTS: Anthropometric indices measured were height, body weight, waist girth, hip girth, triceps and subscapular skinfold thicknesses. Classical criteria for obesity used were percentage overweight (POW), body mass index (BMI) and percentage body fat. Waist girth, sagittal diameter by CT and waist -hip ratio (WHR) were evaluated as anthropometric surrogates for VAT. The areas of total abdominal fat (TAF), VAT and subcutaneous adipose tissue (SAT) were measured by CT at the level of the umbilicus. Clinical blood biochemistry was analyzed in fasting blood samples of obese boys. RESULTS: Thirty-three boys were classified into a no-complication group, and 42 into a complication group. TAF, VAT and SAT areas were closely associated with age, body size and degree of overweight and adiposity, while VAT=SAT was not. VAT area, sagittal diameter, TAF area and waist girth were closely correlated with alanine aminotransferase, insulin, TG and HDL-C. VAT=SAT, BMI, SAT area, WHR, percentage body fat and POW were less closely associated with these biochemical indices. The descending order of the values of area under the curve for the ROC curves were as follows: VAT > sagittal diameter > TAF > VAT=SAT > waist girth > BMI > WHR > percentage body fat > POW. Both VAT area and VAT=SAT gave > 80% of sensitivity and specificity. Among the anthropometric indices studied, the sagittal diameter was the best surrogate of visceral fat measure. The sensitivity and specificity for the rest of the anthropometric indices were in an unsatisfactory range. The threshold values for VAT area, VAT=SAT and sagittal diameter were 58.0 cm 2 , 0.276 and 19.2 cm, respectively. CONCLUSION: The threshold values for VAT area, VAT=SAT and sagittal diameter for detecting biochemical complication in Japanese obese boys were lower than the respective values reported in adults. These values can be used for classifying the obese boys into two types: those with medical problem and those without.

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To determine whether decrease in serum antioxidants contributes to the increased oxidative stress, we measured the antioxidant activity (AOA), total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in the serum of diabetic rats. AOA was assayed as the ability of serum to inhibit lipid autoxidation in brain homogenates. TRAP was assayed as the ability to delay lipid peroxidation induced by an azo initiator. Antioxidants measured were ceruloplasmin, unsaturated iron binding capacity (UIBC) and albumin as components of AOA; and uric acid, protein sulfhydryl and alpha-tocopherol as components of TRAP. AOA was decreased markedly in the diabetics due to the decrease in ceruloplasmin, UIBC and albumin. On the other hand, the directly measured TRAP in the diabetics was unaltered. Uric acid and alpha-tocopherol were increased in the diabetics. However, decrease in unidentified scavengers offset the increase brought about by those antioxidants These results suggest that the decreased metal binding capacity contributes to the increased oxidative stress in the diabetic rats.