Mature Adipocytes Inhibit In Vitro Differentiation of Human Preadipocytes via Angiotensin Type 1 Receptors

摘要

Recent studies suggest that angiotensin Ⅱ (Ang Ⅱ) plays a role in the adipogenesis of murine preadipo-eytes. Here, we examined the role of Ang Ⅱ for the differentiation of primary cultured human preadipo-cytes. 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 preadipo-cytes by maturing adipocytes.