A novel adipokine CTRP1 stimulates aldosterone production

Abstract

Complement-C1q TNF-related protein 1 (CTRP1), a member of the CTRP superfamily, is expressed at high levels in adipose tissues of obese Zucker diabetic fatty (fa/fa) rats, and CTRP1 expression is induced by proinflammatory cytokines, including TNF-alpha and IL-1beta. In the present study, we investigated stimulation of aldosterone production by CTRP1, since it was observed that CTRP1 was specifically expressed in the zona glomerulosa of the adrenal cortex, where aldosterone is produced. Increased aldosterone production by CTRP1 in cells of the human adrenal cortical cell line H295R was dose-dependent. Expression levels of aldosterone synthase CYP11B2 were examined to investigate the molecular mechanisms by which CTRP1 enhances the production of aldosterone. The expression of CYP11B2 was greatly increased by treatment with CTRP1, as was the expression of the transcription factors NGFIB and NURR1, which play critical roles in stimulation of CYP11B2 gene expression. It was also revealed that angiotensin II-induced aldosterone production is, at least in part, mediated by the stimulation of CTRP1 secretion, not by the increase of CTRP1 mRNA transcription. In addition, the levels of CTRP1 were significantly up-regulated in hypertensive patients' serum. As CTRP1 was highly expressed in obese subjects as well as up-regulated in hypertensive patients, CTRP1 may be a newly identified molecular link between obesity and hypertension.

Podocyte-specific Expression of C1q/TNF-α Related Protein 1 in Mice

“…Rabbit anti-CTRP1 polyclonal antibody was prepared for immunohistochemistry [13,14]. Briefly, mouse CTRP1 cDNA encoding the collagen repeat domain was introduced into the pET-28a bacterial expression vector (Novagen, Darmstadt, Germany), which was then transformed into E. coli strain BL21(λDE3).…”

Role of aldosterone and angiotensin II in insulin resistance: an update

“…Interestingly, a recent experimental study demonstrates that complement-C1q TNF-related protein 1 (CTRP1), a novel adipokine, that shares structural homology with adiponectin, stimulates aldosterone production in Zucker diabetic fatty rats. 20 Conversely aldosterone and MR may be involved in adipose tissue regulation, as aldosterone promotes achievement of the white adipose phenotype in a MR-dependent manner, possibly via activation of Peroxisome Proliferator Activated Receptor gamma in experimental conditions. 21 On the other hand, the role of an active local RAAS appears to be of paramount importance in the relationship between obesity, insulin resistance and HTN, as there is abundant evidence demonstrating that adipose tissue expresses a functional RAAS.…”

Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice

“…Additionally, the injection of recombinant CTRP1 reduces the blood glucose levels in mice. 17,18 CTRP3 acts as an anti-inflammatory factor that inhibits lipopolysaccharide (LPS)-mediated inflammation by inhibiting the binding of LPS to toll like receptor 4 (TLR4)/ MD-2 on monocytes and adipocytes. 19,20 CTRP9 reduces the blood glucose levels and insulin resistance in mice, and recombinant CTRP9 activates AMP activated kinase, Akt and p42/44 mitogen activated protein kinase in C2C12 myotubes.…”