Proteasome Subunits mRNA Expressions Correlate With Male BMI: Implications for a Role in Obesity

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 α 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.