Differential expression of a novel seven transmembrane domain protein in epididymal fat from aged and diabetic mice

To identify novel seven transmembrane domain proteins from 3T3-L1 adipocyte s, we used PCR to amplify 3T3-L1 adipocyte complementary DNA (cDNA) with pr imers homologous to the N- and C-termini of pancreatic glucagon-like peptid e-1 (GLP-1) receptor. We screened a cDNA library prepared from fully differ entiated 3T3-L1 adipocytes using a 500-bp cDNA PCR product probe. Herein de scribes the isolation and characterization of a 1.6-kb cDNA clone that enco des a novel 298-amino acid protein that we termed TPRA40 (transmembrane dom ain protein of 40 kDa regulated in adipocytes). TPRA40 has seven putative t ransmembrane domains and shows little homology with the known GLP-1 recepto r or with other G protein-coupled receptors. The levels of TPRA40 mRNA and protein were higher in 3T3-L1 adipocytes than in 3T3-L1 fibroblasts. TPRA40 is present in a number of mouse and human tissues. Interestingly, TPRA40 m RNA levels were significantly increased by 2- to 3-fold in epididymal fat o f 24-month-old mice us. young controls as well as in db/db and ob/ob mice v s, nondiabetic control littermates. No difference in TPRA40 mRNA levels was observed in brain, heart, skeletal muscle, liver, or kidney. Furthermore, no difference in TPRA40 expression was detected in brown fat of ob/ob mice when compared with age-matched controls. Taken together, these data suggest that TPRA40 represents a novel membrane-associated protein whose expressio n in white adipose tissue is altered with aging and type 2 diabetes.