Angiotensin II Receptors in Human Preadipocytes: Role in Cell Cycle Regulation

Abstract

The role of angiotensin II (AII) in human preadipocyte physiology has been investigated in primary cultures from human adipose tissue. Receptor binding studies indicated that human preadipocytes express a high affinity AII binding site of the AT1 subtype, as binding of 125I-labeled [Sar1,Ile8]AII was rapid, saturable, and specific. As AII has previously been demonstrated to affect the cell cycle in adrenal and cardiac cells, the effect of AII on regulation of cycle progression was examined in human preadipocytes. Stimulation of preadipocytes with AII resulted in G1 phase progression of the cell cycle, as determined by flow cytometric analysis. AII treatment was associated with induction of expression of the messenger RNA for the cell cycle regulatory protein cyclin D1 in a dose-dependent manner. Pretreatment of cells with subtype-selective AT receptor ligands before AII stimulation indicated that the cyclin response was mediated via the AT1 receptor. The identity of the cells as preadipocyte was verified by culture in a defined differentiation medium, observing both leptin message expression and triglyceride accumulation by flow cytometry. These findings indicate that AII has early, receptor-mediated effects on cell cycle progression in human preadipocytes that may contribute to differentiation to the adipocyte phenotype.

Comparative expression analysis of the renin–angiotensin system components between white and brown perivascular adipose tissue

“…Adipose tissue and adipocytes contain most of the components of the RAS giving rise to local Ang II synthesis at the tissue level (Saye et al 1993, Harp & DiGirolamo 1995, Crandall et al 1999, Engeli et al 1999, Schling et al 1999. Previously, the vast majority of studies investigating the expression of RAS components in adipose tissue have been performed in subcutaneous and visceral fat mainly obtained from epididymal and retroperitoneal tissues respectively.…”

“…The angiotensin receptor subtype that is most abundantly expressed in both WAT (Burson et al 1994, Cassis et al 1996, Crandall et al 1999, Adams et al 2002 and BAT (Cassis et al 1996) is the AT 1 receptor subtype. Cassis et al (1996) described that WAT contains a higher number of AT 1 receptors than BAT.…”

Differentiation and characterization of human facial subcutaneous adipocytes

“…Although we used published methods to isolate subcutaneous white adipocytes., 23,25 the isolation procedure could potentially contain various mesenchymal cell types and adipose progenitors at various levels of lineage progression. Because most of the cultured cells exhibited a high degree of differentiation in the presence of rosiglitazone, we concluded that the preadipocytes isolated were committed unipotent post-mitotic adipose progenitors or even unipotent adipose progenitors.…”

“…The cells were isolated and cultured as previously described. 23,25 Tissue was obtained from four different donors for facial adipocytes and 5 different donors for abdominal adipocytes. All donors were females, age 45-60 y and the abdominal tissues were from individuals with BMI higher than 25.…”

Fat cell metabolism: Insulin, fatty acids, and renin

“…The focus of research in my laboratory has revolved around the existence of a local renin-angiotensin system in adipose tissue. Interestingly, the adipocyte is one of the few cell types that possess not only all of the synthetic machinery necessary for Ang II production, but also house the AT1 receptor subtype demonstrated to mediate the majority of the physiologic responses to Ang II [33][34][35]. Previous studies in our laboratory have demonstrated the presence of high levels of angiotensinogen mRNA in rat brown and white adipose tissue [36•].…”