cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue

1 Service de Biochimie et de Biologie Moléculaire de la Faculté de Médecine Paris-Ile-de-France-Ouest, Université René Descartes, F75270 Paris; 2 Hôpital de Poissy, F78303 Poissy; and 3 Hôpital R Poincaré, F92380 Garches, France Submitted 25 April 2003 ; accepted in final form 21 October 2003 The adipose renin-angiotensin system (RAS) has been assigned to participate in the control of adipose tissue development and in the pathogenesis of obesity-related hypertension. In adipose cells, the biological responses to -adrenergic stimulation are mediated by an increase in intracellular cAMP. Because cAMP is known to promote adipogenesis and because an association exists between body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in rat adipose tissue. Exposure of primary cultured differentiated preadipocytes to the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or cAMP-stimulating agents (forskolin and IBMX) results in a significant increase in ATG mRNA levels. In adipose tissue fragments, 8-BrcAMP also increases ATG mRNA levels and protein secretion, but not in the presence of the protein kinase A inhibitor H89. The addition of isoproterenol, known to stimulate the synthesis of intracellular cAMP via -adrenoreceptors, had the same stimulatory effect on ATG expression and secretion. These results indicate that cAMP in vitro upregulates ATG expression and secretion in rat adipose tissue via the protein kinase A-dependent pathway. Further studies are required to determine whether this regulatory pathway is activated in human obesity, where increased sympathetic tone is frequently observed, and to elucidate the importance of adipose ATG to the elevated blood pressure observed in this pathological state. angiotensinogen expression; cyclic adenosine 5'-monophosphate Address for reprint requests and other correspondence: V. Serazin, Service de Biologie Médicale, C.H.I. Poissy/St Germain en Laye, 10, rue du Champ Gaillard, F78303 Poissy, France (E-mail: valerie_serazin{at}hotmail.com ).