Regulation by glucocorticoids of angiotensinogen gene expression and secretion in adipose cells

Abstract

Adipose cells are an important source of angiotensinogen (AT). Its activation product, angiotensin II, stimulates in vitro and in vivo the production and release of prostacyclin which acts as a potent adipogenic signal in promoting the terminal differentiation of preadipocytes to adipocytes. Since glucocorticoids are known to promote adipose cell differentiation in vitro as well as in vivo, their role in the regulation of AT gene expression and secretion has been investigated in cultured Ob1771 mouse adipose cells. In contrast with liver cells, which are the major source of AT and the target of several hormones for the regulation of its expression, adipose cells are only responsive to glucocorticoids, which are able to up-regulate AT gene expression and AT secretion rapidly and dose-dependently. On exposure to glucocorticoids, accumulation of AT mRNA appears primarily to be due to transcriptional activation of the gene and is parallelled by secretion of the protein. Similar results on AT mRNA expression and AT secretion were obtained using explants of rat adipose tissue ex vivo demonstrating a major if not exclusive mechanism of regulation of AT production by glucocorticoids in mature adipose cells. Together these results provide a potential link between glucocorticoids, AT, the growth of adipose tissue and increased blood pressure.

Metabolic action of peroxisome proliferator-activated receptor γ agonism in rats with exogenous hypercorticosteronemia

“…In a pilot experiment using conditions identical to those of the present study, portal blood CORT was shown to be highly correlated with that in trunk blood (r ¼ 0.92, P ¼ 0.0002, n ¼ 10), confirming that visceral WAT draining into the portal vein had effectively been exposed to high CORT levels. Higher expression levels in RWAT of the GC target gene angiotensinogen 21 (1.5-fold) further confirmed the functionality of adipose exposure to exogenous high CORT. RSG did not significantly influence serum CORT concentrations, as determined by averaging two separate samples taken at day 11 and at the end of the treatment period, and slightly but significantly reduced (-11%, Po0.04) adrenal weight in vehicle-implanted animals (data not shown).…”

Steroid Responsiveness of Renal Epithelial Cells

“…We demonstrate that dexamethasone induced translocation of GR from the cytosol to the nucleus, suggesting that the first part of the signaling pathway is intact. Next, we examined the transactivation capacity of dexamethasone on the expression of AGT, a gene that is positively regulated by glucocorticoids in various cell types, including rat proximal tubular epithelial cells (27)(28)(29). Stimulation of gene transcription is thought to be mediated via acetylation of core histones on highly conserved lysine residues (2, 30).…”

“…Next, we performed semiquantitative ChIP assays to study AGT expression, which is known to be stimulated by glucocorticoids in vitro and in vivo (27)(28)(29). Sequence analysis of the AGT promoter (Ϫ1223 to ϩ35) identified the presence of three putative GR-binding sites.…”

Adipose tissue as an endocrine organ

“…23 Our results have shown that, in contrast with liver cells (which have been reported to respond positively to glucocorticoids), estrogens, tri-iodothyronine (T 3 ), growth hormone and angiotensin II, Ob1771 adipocytes were only responsive to glucocorticoids for up-regulation of AT gene expression and AT secretion. 24 Moreover, since an association exists between body mass index, hypertension and insulinresistance, the role of insulin on the regulation of AT gene expression and AT secretion was also examined in culture mouse adipocytes. Within a physiological range of concentrations (1 ± 17 nM), insulin exerted a negative effect on the abundance of AT mRNA and the secretion of AT from adipocytes.…”