Adrenomedullin and its receptor components in adipose tissues: Differences between white and brown fats and the effects of adrenergic stimulation

Male Sprague–Dawley rats were subcutaneously injected with 2.5 mg/kg phenylephrine or 2.5 mg/kg isoproterenol or both (2.5 mg/kg for each drug) for 4 days, twice a day. Samples of scapular brown adipose tissue (BAT) and epididymal white adipose tissue (WAT) were collected for the measurement of adrenomedullin (AM) levels and the gene expression of preproAM, calcitonin receptor like receptor (CRLR) and its activity modifying proteins (RAMPs) by radioimmunoassay and RT-PCR. These values were compared with those in the rats that received 0.9% saline. The gene expression of AM and AM receptor components in BAT are much less than that in epididymal WAT. In BAT there were an increase in AM peptide level after a combined treatment of α1 and β adrenoceptor agonists and increases in preproAM mRNA levels for rats treated with α1 and β receptor agonists alone or in combination. Both CRLR and RAMP2 mRNA levels of αβ group were increased significantly. In WAT, AM peptide level, RAMP1 and RAMP2 mRNA expression levels were augmented in the α group while CRLR mRNA level was enhanced in the β group. The levels of AM, its receptor and RAMPs are much less in BAT than in WAT but adrenergic stimulation has a greater effect on the AM and its receptor components in BAT than those in WAT. AM stimulates lipolysis and increases the level of uncoupling protein-1 (UCP-1) in BAT. It may therefore enhance thermogenesis by increasing the availability of free fatty acids substrate as well as the UCP-1 level on the mitochondrial membrane.