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Horm Metab Res 2008; 40(3): 165-171
DOI: 10.1055/s-2007-1022547
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Expression of ATRAP in Adipocytes and Negative Regulation by β-Adrenergic Stimulation of JAK/STAT

S. Westphal 1 , 2 [*] , N. Perwitz 1 [*] , K. A. H. Iwen 1 , D. Kraus 1 , R. Schick 2 , M. Fasshauer 3 , J. Klein 1
  • 1Department of Internal Medicine I, University of Lübeck, Germany
  • 2Department of Internal Medicine, Federal Armed Forces Hospital, Ulm, Germany
  • 3Department of Internal Medicine III, University of Leipzig, Germany
Further Information

Publication History

received 20.04.2007

accepted 13.08.2007

Publication Date:
30 January 2008 (online)

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Abstract

Sympatho-adrenergic activity and the renin-angiotensin system are considered critical regulators of obesity and hypertension. The novel angiotensin II type 1 receptor-associated protein (ATRAP) has been demonstrated to modulate angiotensin II signalling in smooth muscle cells and cardiomyocytes. Adipose tissue expresses important renin angiotensin system components and contributes to cardiometabolic disease. However, ATRAP expression and regulation in adipocytes are unknown. We investigated expression of this novel modulator of angiotensin signalling and its regulation by β-adrenergic receptors. We found ATRAP to be expressed in differentiated brown and white adipocytes. Stimulation of β-adrenoceptors strongly suppressed ATRAP expression. We hypothesised a role for JAK/STAT signalling elements. Indeed, β3-adrenergic stimulation robustly stimulated both STAT1 and STAT3 phosphorylation in a time- and dose-dependent manner. This effect was abrogated by inhibition of PKA and JAK2 signalling. Moreover, inhibition of JAK/STAT and PKA signalling reversed the β3-adrenergic suppression of ATRAP expression. This study provides the first evidence for expression and adrenergic regulation of the angiotensin II signalling modulator ATRAP in adipocytes. Further, it indicates a novel regulatory link between β-adrenergic and JAK/STAT signalling.

Key words

adipocyte - angiotensin II - ATRAP - beta-adrenergic - JAK/STAT - RAS

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1 These authors contributed equally to this work

Correspondence

J. KleinMD 

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