First Case of Canine Infection with Hepatozoon canis (Apicomplexa: Haemogregarinidae) in the Republic of Korea.

This report describes a dog infected with Hepatozoon canis, the first canine infection in the Republic of Korea. A 2-year-old intact male Maltese dog presented with anorexia and depression. Physical examinations revealed mild dehydration and hyperthermia (39.8°C), and blood analysis showed pancytopenia. Diff-Quik staining of blood smear specimens showed the presence of ellipsoidal shaped structures (gamonts of H. canis) within a small number of neutrophils. Real-time PCR analysis using whole blood confirmed infection by H. canis. The clinical condition of the dog improved after symptomatic treatment and administration of doxycycline. Although a molecular epidemiologic survey in Korea showed H. canis infection of dogs, to our knowledge this is the first report of a dog infection in Korea molecularly shown to be H. canis.

Adipocyte-Specific Deficiency of De Novo Sphingolipid Biosynthesis Leads to Lipodystrophy and Insulin Resistance.

Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes. Adipocyte-specific SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass. Fatty acids that were destined for the adipose tissue were instead shunted to liver and caused hepatosteatosis. This impaired fat distribution caused systemic insulin resistance and hyperglycemia, indicating severe lipodystrophy. Mechanistically, sphingosine 1-phosphate (S1P) was reduced in the adipose tissues of aSPTLC2 KO mice, and this inhibited adipocyte proliferation and differentiation via the downregulation of S1P receptor 1 and decreased activity of the peroxisome proliferator-activator receptor γ. In addition, downregulation of SREBP (sterol regulatory element-binding protein)-1c prevented adipogenesis of aSPTLC2 KO adipocytes. Collectively, our observations suggest that the tight regulation of de novo sphingolipid biosynthesis and S1P signaling plays an important role in adipogenesis and hepatosteatosis.

Circulating free fatty acids inhibit food intake in an oleate-specific manner in rats.

Previous rodent studies showed that when injected into the brain, free fatty acids (FFAs) reduced food intake in an oleate-specific manner. The present study was performed to test whether food intake is regulated by circulating FFAs in an oleate-specific manner. Male Wistar rats received an intravenous infusion of olive, safflower, or coconut oil (100mg/h), together with heparin, to raise circulating oleate, linoleate, or palmitate, respectively, and their effects on overnight food intake were evaluated. Compared to other oils, olive oil infusion showed a significantly greater effect to reduce food intake (P<0.01). Total caloric intake, the sum of the calories from the diet and infused oil, was significantly reduced with olive oil (P<0.01) but not with coconut or safflower oil infusion, suggesting an oleate-specific effect on caloric intake. To further test this idea, different groups of rats received an intravenous infusion of oleate, linoleate, or octanoate (0.5mg/h). Oleate infusion decreased overnight food intake by 26% (P<0.001), but no significant effect was seen with linoleate, octanoate, or vehicle infusion (P>0.05). The effects of olive oil or oleate infusion could not be explained by changes in plasma glucose, insulin, leptin, or total FFA levels. The olive oil effect on food intake was not reduced in vagotomized rats, suggesting that oleate sensing may not involve peripheral sensors. In contrast, olive oil's effect was attenuated in high-fat-fed rats, suggesting that this effect is regulated (or impaired) under physiological (or pathological) conditions. Taken together, the present study provides evidence that circulating oleate is sensed by the brain differentially from other FFAs to control feeding in rats.

The Gender Association of the SIRT1 rs7895833 Polymorphism with Pediatric Obesity: A 3-Year Panel Study.

OBJECTIVES: Sirtuin 1 (SIRT1), a longevity-associated gene, has pleiotropic functions. We investigated whether SIRT1 variation is associated with pediatric obesity. METHODS: During 3 years of follow-up of 219 children (101 boys, 118 girls) aged 8 or 9 years at baseline, obesity parameters such as anthropometrics, plasma lipid and insulin resistance profiles, and nutrient intakes were analyzed with regard to 3 genotypes of SIRT1 rs7895833 (GG, GA, and AA). RESULTS: The prevalence of obesity including overweight had increased from 18.3% (in 2007) to 25.1% (in 2010), and the incidence of obesity over 3 years from nonobesity at the baseline was 11.7%. In the obesity group (BMI >85th percentile) that had been nonobese 3 years before, the frequency of the GA+AA genotypes was higher than that of the GG genotype. Among the total number of subjects, the values for criteria for obesity such as BMI and waist circumference were higher in the GA+AA group than in the GG group. In boys, the reductions in total cholesterol and low-density lipoprotein cholesterol levels in the GG group were considerably greater than those in the GA+AA group, even though the changes in carbohydrate, fat, and protein intake in the GG group were higher than in the GA+AA group. In girls, the reductions in fasting blood sugar and homeostatic model assessment insulin resistance (HOMA-IR) levels were greater in the GA+AA group than in the GG group, despite unchanged energy intakes over 3 years. CONCLUSIONS: We identified an association between SIRT1 variation and pediatric obesity in Korean children with a gender difference.

Sodium meta-arsenite ameliorates hyperglycemia in obese diabetic db/db mice by inhibition of hepatic gluconeogenesis.

Sodium meta-arsenite (SA) is implicated in the regulation of hepatic gluconeogenesis-related genes in vitro; however, the effects in vivo have not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabetic db/db mice were orally intubated with SA (10 mg kg(-1) body weight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabetic db/db mice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver of SA-treated diabetic db/db mice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α) mRNA. Small heterodimer partner (SHP) mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated diabetic db/db mice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia in db/db mice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1.

The effects of uncoupling protein-1 genotype on lipoprotein cholesterol level in Korean obese subjects.

Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism of the UCP-1 gene on the plasma lipid profiles in 190 Korean obese subjects with a body mass index (BMI) more than 30 kg/m2. Height, weight, BMI, wait-to-hip ratio (WHR), obesity index, and body composition were measured and genotype of UCP-1 was analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. Serum concentrations of fasting glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. The frequencies of UCP-1 genotypes were AA type, 22.1%; AG type, 53.7%; and GG type, 24.2%; and the frequency of G allele was 0.51. Among many parameters, diastolic blood pressure (DBP) (P = .023) and low-density lipoprotein (LDL) cholesterol (P = .011) were significantly higher in AG and GG types compared with AA type, whereas HDL cholesterol was significantly lower in GG type compared with other types (P < .05). Atherogenic index was significantly higher in GG type compared with AA type (P = 0.027). LDL-to-HDL cholesterol ratio was significantly increased in the order of AA < AG < GG types (P = .001). When the subjects were divided into a normal group and a hyper-LDL cholesterolemia group by LDL cholesterol level of 3.626 mmol/L (140 mg/dL), the frequency of hyper-LDL cholesterolemia was significantly higher in GG type compared with other types by Fisher's exact (chi-square) test (P = .05). When logistic regression analysis was conducted to find the risk factors of hyper-LDL cholesterolemia, the odds ratio was 4.115 (P = .03) for GG type of UCP-1 gene. These results suggest that the GG type of the UCP-1 gene has a strong association with increased LDL cholesterol level and might be a significant risk factor for hyper-LDL cholesterolemia among Korean obese subjects.

Molecular analysis of HLA class II-associated susceptibility to neuroinflammatory diseases in Korean children.

The work was done to study immunogenetic peculiarities of neuroinflammatory diseases among Korean children. A total of 13 children with neuroinflammatory diseases (8 males and 5 females; mean age 4.6 +/-2.6 yr) were consecutively recruited. Geno-mic typing was performed on their HLA DRB/HLA DQB genes using PCR-SSOP/SSP techniques with gel immunoelectrophoresis. The frequencies of HLA-DR1 *15 in children with acute disseminated encephalomyelitis (ADEM) (31%) and DQB1 *06 in other neuroinflammatory diseases (38%) were significantly increased compared with control subjects. The frequencies of HLA-DRB3 * 0202 (100%), HLA-DRB1 * 1302 (67%), HLA-DRB3 * 0301 (67%), and HLA-DQB1 * 0301 (67%) were significantly increased in children with multiple sclerosis and the frequencies of HLA-DRB1 * 1501 (40%) and HLA-DRB5 * 0101 (40%) were significantly increased in children with ADEM. HLA-DRB1 * 1401, HLA- DRB3 * 0202, and HLA-DQB1 * 0502 were found in children with acute necrotizing encephalopathy. In conclusion, HLA-DR1 * 15 and DQB1 * 06 may be involved in susceptibility to inflammation in Korean children. The frequencies of HLA-DRB1 * 1501, HLA-DRB5 * 0101, HLA-DRB3 * 0301, and HLA-DQB1* 0602 were not as high in Korean children with multiple sclerosis as in western children. However, HLA-DRB3 * 0202 was seen in all children with multiple sclerosis. Our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in Korean is distinctly different from the ones in western countries. Further studies are necessary to confirm this finding.