Renin receptor expression in human adipose tissue

1 Institute National de la Santé et de la Recherche Médicale UMR 626, Marseille; 2 Faculté de Médecine, Université de la Méditerranée, Marseille; 3 Centre d’Investigation Clinique, Assistance Publique-Hôpitaux de Marseille, Marseille; 4 Service de Gynécologie-Obstétrique, CHU Nord, Assistance Publique–Hôpitaux de Marseille, Marseille; 5 Institut National de la Santé et de la Recherche Médicale U36, Collège de France, Paris, France Submitted 27 June 2006 ; accepted in final form 22 August 2006 Adipose tissue synthesizes all components of the renin-angiotensin system. The renin receptor (RenR) is able, on renin binding, to increase its efficiency to generate angiotensin I from angiotensinogen. We demonstrate that RenR is specifically synthesized in the stromal portion of human adipose tissue in both isolated interadipocyte stromal cells and in stromal areas. RenR is expressed at the periphery of cells, strongly suggesting a membranal localization. RenR protein expression in primary cultures of human stromal cells decreased significantly during differentiation, whereas RenR mRNA levels did not change, demonstrating that RenR was expressed in both preadipocyte and nonpreadipocyte cells, and was regulated at a posttranscriptional level. Double-labeling immunohistochemistry of human adipose tissue sections revealed that RenR was colocalized with renin, whereas incubation of 3T3-L1, a preadipocyte cell line, with renin stimulated the phosphorylation state of the intracellular signaling pathway ERK 1/2, and short exposure of human adipose stromal cells in primary culture to renin was followed by a long-lasting dose-dependent increase of angiotensin I generation, indicating that adipose RenR is functional. We show, using a large set of human adipose tissue biopsies, that RenR expression was increased in visceral compared with subcutaneous adipose tissue of lean and obese patients. Taken together with our finding that RenR was colocalized with plasminogen activator inhibitor type 1, the main inhibitor of the fibrinolytic system in visceral adipose tissue, the above-mentioned data suggest that RenR plays a role in obesity-induced visceral adipose tissue accumulation and its accompanying cardiovascular complications. immunohistochemistry; adipocyte differentiation; reverse transcriptase-polymerase chain reaction Address for reprint requests and other correspondence: M. Grino, Inserm UMR 626, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385, Marseille cedex 5, Fran