Mature Adipocytes Inhibit In Vitro Differentiation of Human Preadipocytes via Angiotensin Type 1 Receptors
- From the Max Delbrück Center for Molecular Medicine, HELIOS Klinikum-Berlin, Franz Volhard Clinic, Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany
Recent studies suggest that angiotensin II (Ang II) plays a role in the adipogenesis of murine preadipocytes. Here, we examined the role of Ang II for the differentiation of primary cultured human preadipocytes. Preadipocytes were isolated from human adipose tissue and stimulated to differentiate. Quantitation of gene expression during adipogenesis was performed for renin-angiotensin system (RAS) genes. The influence of the RAS on adipogenic differentiation was investigated by addition of either angiotensinogen (AGT), Ang II, or angiotensin receptor antagonists to the differentiation medium. We also examined the influence of adipocytes on adipogenesis by co-culture experiments. Expression of the RAS genes AGT, renin, angiotensin-converting enzyme, and Ang II type 1 receptor increased during adipogenesis. Stimulation of the Ang II type 1 receptor by Ang II reduced adipose conversion, whereas blockade of this receptor markedly enhanced adipogenesis. Adipocytes were able to inhibit preadipocyte differentiation in the co-culture, and this effect was abolished by blockade of the Ang II type 1 receptor. This finding points to a functional role of the RAS in the differentiation of human adipose tissue. Because AGT secretion and Ang II generation are characteristic features of adipogenesis, we postulate a paracrine negative-feedback loop that inhibits further recruitment of preadipocytes by maturing adipocytes.
Address correspondence and reprint requests to Arya M. Sharma, MD, Franz-Volhard Klinik-Charité, Wiltberg Strasse 50, 13125 Berlin, Germany. E-mail:.
Received for publication 5 October 2001 and accepted in revised form 12 March 2002.
A.M.S. is a member of the irbesartan advisory panel and has received honoraria for speaking engagements from Sanofi-Synthelabo. A.M.S. has also received funds from Sanofi-Synthelabo to conduct studies with irbesartan on adipocyte function and other aspects of metabolism.
AGT, angiotensinogen; Ang, angiotensin; DMEM, Dulbecco’s modified Eagle’s medium; HBSS, Hank’s balanced salt solution; IBMX, isobutyl methyl xanthine; IRS-1, insulin receptor substrate 1; PI, phosphatidylinositol; PPAR-γ, peroxisome proliferator-activated receptor-γ; RAS, renin-angiotensin system.