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Research Article Free access | 10.1172/JCI1915

Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action.

M C Zennaro, D Le Menuet, S Viengchareun, F Walker, D Ricquier, and M Lombès

INSERM U 246, Institut Fédératif de Recherche Cellules Epithéliales, Faculté de Mé decine Xavier Bichat, Paris, France.

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INSERM U 246, Institut Fédératif de Recherche Cellules Epithéliales, Faculté de Mé decine Xavier Bichat, Paris, France.

Find articles by Le Menuet, D. in: JCI | PubMed | Google Scholar

INSERM U 246, Institut Fédératif de Recherche Cellules Epithéliales, Faculté de Mé decine Xavier Bichat, Paris, France.

Find articles by Viengchareun, S. in: JCI | PubMed | Google Scholar

INSERM U 246, Institut Fédératif de Recherche Cellules Epithéliales, Faculté de Mé decine Xavier Bichat, Paris, France.

Find articles by Walker, F. in: JCI | PubMed | Google Scholar

INSERM U 246, Institut Fédératif de Recherche Cellules Epithéliales, Faculté de Mé decine Xavier Bichat, Paris, France.

Find articles by Ricquier, D. in: JCI | PubMed | Google Scholar

INSERM U 246, Institut Fédératif de Recherche Cellules Epithéliales, Faculté de Mé decine Xavier Bichat, Paris, France.

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Published March 15, 1998 - More info

Published in Volume 101, Issue 6 on March 15, 1998
J Clin Invest. 1998;101(6):1254–1260. https://doi.org/10.1172/JCI1915.
© 1998 The American Society for Clinical Investigation
Published March 15, 1998 - Version history
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Abstract

Aldosterone is a major regulator of salt balance and blood pressure, exerting its effects via the mineralocorticoid receptor (MR). To analyze the regulatory mechanisms controlling tissue-specific expression of the human MR (hMR) in vivo, we have developed transgenic mouse models expressing the SV40 large T antigen (TAg) under the control of each of the two promoters of the hMR gene (P1 or P2). Unexpectedly, all five P1-TAg founder animals died prematurely from voluminous malignant liposarcomas originating from brown adipose tissue, as evidenced by the expression of the mitochondrial uncoupling protein ucp1, indicating that the proximal P1 promoter was transcriptionally active in brown adipocytes. No such hibernoma occurred in P2-TAg transgenic mice. Appropriate tissue-specific usage of P1 promoter sequences was confirmed by demonstrating the presence of endogenous MR in both neoplastic and normal brown adipose tissue. Several cell lines were derived from hibernomas; among them, the T37i cells can undergo terminal differentiation into brown adipocytes, which remain capable of expressing ucp1 upon adrenergic or retinoic acid stimulation. These cells possess endogenous functional MR, thus providing a new model to explore molecular mechanisms of mineralocorticoid action. Our data broaden the known functions of aldosterone and suggest a potential role for MR in adipocyte differentiation and regulation of thermogenesis.

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