RESUMO
Obesity as well as its associated chronic diseases and adverse health consequences such as type 2 diabetes mellitus, dyslipidemia, hypertension, and coronary artery disease are afflicting middle-aged adults and an ever greater number of children globally. We planned to investigate new obesity-related factors using proteomics approaches in a randomly selected three high and three low BMI samples of Epstein-Barr-transformed B (EBV-B) lymphoblastoid cell lines prepared from two groups of young Japanese men with different BMI. To search novel obesity-related factors, comparisons of protein expressions between high and low BMI groups were carried out by two-dimensional gel electrophoresis (2-DE). Gene transcripts of proteasome subunits found out from 2-DE were further determined by quantitative real-time PCR. Results from proteomics approach showed that the expression of proteasome alpha subunit type 5 (PSMA5) was significantly lower in the high BMI male group than in those with low BMI (P < 0.05). To validate these results, we expanded the study to include 20 more men and used real-time PCR to quantify the mRNA expression level in their EBV-B cells. Both PSMA5 and PSMA2 of EBV-B cells showed negative correlation with BMI. Furthermore, the mRNA levels measured in the peripheral blood B lymphocytes for many proteasome subunits in 75 healthy men and women showed significant negative correlation with BMI in healthy men. Our findings suggest that proteasome expression may play a key role in obesity.
Assuntos
Obesidade/genética , Complexo de Endopeptidases do Proteassoma/genética , Subunidades Proteicas/genética , RNA Mensageiro/genética , Índice de Massa Corporal , Linhagem Celular , Primers do DNA , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , Reação em Cadeia da Polimerase , Complexo de Endopeptidases do Proteassoma/sangue , Subunidades Proteicas/sangue , Valores de Referência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
UCP-1 is suggested to have important roles for thermogenesis and energy expenditure. To elucidate whether the A-3826G polymorphism that is located in the 5' flanking region of the UCP-1 gene has roles in healthy young people, the polymorphism was genotyped among 251 young Japanese men whose mean age is 22.7 years old. We analyzed relationship between the A-3826G polymorphism and body mass index (BMI) or six biochemical parameters, serum concentration of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, triglyceride (TG), asparatate aminotransferase (AST), alanine aminotransferase (ALT), fasting plasma glucose. The genotype frequencies were observed at the frequencies of 24.3% for AA, 48.2% for AG and 27.5% for GG, respectively. When BMI and the biochemical parameters were compared by ANOVA among individuals with each genotype, the statistical difference was observed only for BMI (P=0.016). Bonferroni's test demonstrated that the men with the AG genotype have higher BMI than those with the AA genotype (22.4+/-2.8 vs. 21.4+/-2.2) (P=0.04). The individuals with the AG genotype also showed trend to have higher BMI than those with the GG, although the difference was not statistically apparent (22.4+/-2.8 vs. 21.5+/-2.3) (P=0.07). Our results indicated that the young healthy Japanese men with the AG heterozygote showed higher BMI than those with other genotypes.
