Cerebral antioxidant enzyme increase associated with learning deficit in type 2 diabetes rats.

In this study, we examined alterations in the enzymatic antioxidant defenses associated with learning deficits induced by type 2 diabetes, and studied the effects of the peroxisome proliferator-activated receptor γ agonist pioglitazone on these learning deficits. Learning ability was assessed by visual discrimination tasks in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a model of spontaneous type 2 diabetes. Levels of the antioxidant enzymes glutathione peroxidase (GPx), Cu(2+)-Zn(2+) superoxide dismutase (CuZn-SOD) and manganese SOD were measured in the cortex, hippocampus and striatum. Half the rats received oral pioglitazone (20mg/kg/day) from the early stage of diabetes (22 weeks old) to 27 weeks old. OLETF rats showed learning deficits compared with control, Long-Evans Tokushima Otsuka (LETO) rats. GPx levels in the cortex and hippocampus were increased in OLETF rats compared with LETO rats, with an inverse correlation between GPx in the hippocampus and learning score. CuZn-SOD levels were also increased in the hippocampus in OLETF rats. Pioglitazone reduced blood glucose and increased serum adiponectin levels, but had no effect on learning tasks or antioxidant enzymes, except for CuZn-SOD. These results suggest that an oxidative imbalance reflected by increased brain antioxidant enzymes plays an important role in the development of learning deficits in type 2 diabetes. Early pioglitazone administration partly ameliorated diabetic symptoms, but was unable to completely recover cerebral oxidative imbalance and functions. These results suggest that diabetes-induced brain impairment, which results in learning deficits, may have occurred before the appearance of the symptoms of overt diabetes.

Threshold values of visceral fat and waist girth in Japanese obese children.

BACKGROUND: In order to define the diagnostic criteria for visceral adipose tissue (VAT) accumulation and abdominal obesity in Japanese youths, a cross-sectional, multicenter study was conducted. METHODS: Subjects were 194 boys and 96 girls ranging in age from 6 to 15 years. Obese youths were classified according to the occurrence of abnormal values in serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion was calculated, using the analysis of receiver operating characteristic (ROC) curve. The areas of total abdominal adipose tissue (AT), VAT and subcutaneous adipose tissue (SAT) were estimated by single slice computed tomography at the level of umbilicus. RESULTS: VAT area was greater in boys than it was in girls. The critical values for VAT area and waist circumference in all subjects were 54.8 cm2 and 83.5 cm, respectively. The values for the area under the ROC curves were VAT area > total AT area > waist circumference > SAT area > percentage overweight > percentage body fat. The sensitivity and specificity for VAT area were 90.5 and 79.5%, respectively. Those for waist circumference were high enough (> 70%) for clinical use. In the linear regression analysis assigning VAT area as an independent variable and waist circumference as a dependent variable, the expected value for the waist circumference was 82 cm. CONCLUSION: In Japanese obese youths ranging in age from 6 to 15 years, the diagnostic criteria for the waist circumference was 82 cm, and that for VAT area was 55 cm2.

An MCA/MR syndrome with hypocholesterolemia due to familial hypobetalipoproteinemia: report of a second patient with Nguyen syndrome.

[Nguyen et al. (2003); Am J Med Genet 121A: 109-112] reported a boy with severe hypocholesterolemia due to autosomal dominant hypobetalipoproteinemia (ADBHL) associated with severe growth retardation, mental deficiency, epicanthal folds, a short nose with low nasal bridge and anteverted nares and bilateral partial cutaneous syndactyly of toes 2 and 3. Many of these manifestations resembled those in a mild form of Smith-Lemli-Opitz syndrome (SLOS). We report on a 13-year-old boy with ADHBL, who manifested a SLOS-like phenotype, including mental retardation and a characteristic face, similar to that of a patient reported by [Nguyen et al. (2003); Am J Med Genet 121A: 109-112]. Our patient supports the hypothesis by [Nguyen et al. (2003); Am J Med Genet 121A: 109-112] that ADHBL induced cholesterol deficiency has a significant effect on morphogenesis during embryogenesis, although additional genetic or environmental factors may be required to develop an SLOS-like phenotype in individuals with ADHLB. This is a second case of Nguyen syndrome.

Plasma levels of orexin-a and leptin in obese children.

The present study was designed to determine the plasma level of orexin and its relationship with other metabolic and anthropometric markers in obese children. Forty-seven obese Japanese children, consisting of 31 boys and 16 girls, were enrolled in the study. Their ages were 10.4 ± 0.5 (mean ± s.e.m.) yr, and their percentage overweight was 42.9 ± 1.9%. Blood was drawn after an overnight fast. The age-matched control group consisted of 26 nonobese children, 13 boys and 13 girls. Plasma orexin-A concentration was higher in obese children (17.0 ± 0.4 pg/ml; p<0.001) than in the control children (13.5 ± 1.1 pg/ml). Similarly, plasma leptin concentration was higher in obese children (12.0 ± 1.0 ng/ml; p<0.001) than in the control children (5.2 ± 0.4 ng/ml). There was a highly significant positive correlation between the two parameters in the obese children (r=0.49, p<0.001). Plasma orexin-A level was correlated significantly with waist-to-hip ratio, while leptin level was correlated with percentage overweight, waist circumference and percentage body fat in the obese children. These results suggest that high plasma orexin-A level parallels the leptin level in obese children.

Decrease in serum adiponectin level due to obesity and visceral fat accumulation in children.

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 lipoprotein-cholesterol, 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 +/- 0.6 vs. 10.2 +/- 0.8 mg/L, means +/- SEM, p < 0.001). In 21 obese children whose percent overweight declined during therapy, the adiponectin level increased (p = 0.002). The adiponectin level was correlated inversely with visceral adipose tissue area in obese children (r = -0.531, p < 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.

Increased serum cholesteryl ester transfer protein in obese children.

OBJECTIVE: To determine whether serum cholesteryl ester transfer protein (CETP), which is one of the physiologically active gene products secreted from adipose tissue, is increased and associated with atherogenic lipoprotein profile in obese children. RESEARCH METHODS AND PROCEDURES: Subjects were 42 consecutive outpatient Japanese obese children, 29 boys and 13 girls, ranging in age from 5 to 14 years, and 25 age-matched non-obese children, 13 boys and 12 girls, as the control group for measuring CETP mass. Blood was drawn after an overnight fast and, at the same time, and anthropometric measurements including height, body weight, waist girth, hip girth, and triceps and subscapular skinfold thicknesses were taken. Paired samples were obtained from 15 obese children who underwent psychoeducational therapy. Serum CETP mass was assayed by an enzyme-linked immunosorbent assay. RESULTS: The serum levels of triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol, TC/high-density lipoprotein cholesterol (HDLC), apolipoproteins (apo) B, apo B/apo A(1), and insulin in obese children were significantly higher than the respective reference values. Serum CETP level was approximately 2-fold higher (98.7 +/- 3.6 vs. 50.9 +/- 4.0 nM, means +/- SEM, p < 0.001) in the obese children than in the controls. In 15 obese children, whose percentage of overweight declined during therapy, CETP levels decreased significantly. CETP level was correlated with HDLC, TC/HDLC, and insulin, and with percentage of overweight when the data of the obese and non-obese children were combined. DISCUSSION: CETP is increased and associated with the atherogenic lipoprotein profile in obese children.

A variant of Fine-Lubinsky syndrome: a Japanese boy with profound deafness, cataracts, mental retardation, and brachycephaly without craniosynostosis.

A Japanese boy with a hearing deficit, cataracts, mental retardation, and brachycephaly without craniosynostosis is described. We believe that this patient represents a variant of the Fine-Lubinsky syndrome, and is the first report from a racial group other than Caucasian.