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A novel adipokine CTRP1 stimulates aldosterone production

Jun Ho Jeon^*,1, Kun-yong Kim^**,1, Jae Hyeong Kim^*, Ahmi Baek^*, Hyungin Cho^*, Young Ho Lee, Jong Wan Kim, Dohee Kim, Seung Hyun Han, Jong-Seok Lim^*, Keun Il Kim^*, Do Young Yoon^||, Soo-Hyun Kim^||, Goo Taeg Oh^¶, Eunjoon Kim^** and Young Yang^*,2

^* Research Center for Women’s Disease, Department of Life Science, Sookmyung Women’s University, Seoul, Korea;

Department of Anatomy and Pathology, College of Medicine, Chungnam National University, Daejeon, Korea;

Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea;

Department of Oral Microbiology & Immunology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea;

^|| Department of Bioscience and Biotechnology, Konkuk University, Seoul, Korea;

^¶ Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seodaemoon-gu, Seoul, Korea; and

^** Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon, Korea

²Correspondence: Department of Life Science, Sookmyung Women’s University, Seoul 140–742, Korea. E-mail: yyang{at}sookmyung.ac.kr

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- and IL-1β. 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. Jeon, J. H., Kim, K., Kim, J. H., Baek, A., Cho, H., Lee, Y. H., Kim, J. W., Kim, D., Han, S. H., Lim, J.-S., Kim, K.-I., Yoon, D. Y., Kim, S.-Y., Oh, G. T., Kim, E., Yang, Y. A novel adipokine CTRP1 stimulates aldosterone production.

Key Words: hypertension • adipocytes • obesity • CYP11B2

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