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Originally published In Press as doi:10.1074/jbc.M207229200 on September 4, 2002

J. Biol. Chem., Vol. 277, Issue 45, 42958-42963, November 8, 2002
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Sex-dependent Thermogenesis, Differences in Mitochondrial Morphology and Function, and Adrenergic Response in Brown Adipose Tissue*

Sergio Rodríguez-CuencaDagger , Esperanza Pujol§, Roberto Justo, Margalida Frontera§, Jordi Oliver, Magdalena Gianotti, and Pilar Roca||

From the Departament de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, E-07071 Palma de Mallorca, Spain

Gender-related differences in brown adipose tissue (BAT) thermogenesis of 110-day-old rats were studied by determining the morphological and functional features of BAT. The adrenergic control was assessed by studying the levels of beta 3- and alpha 2A-adrenergic receptors (AR) and by determining the lipolytic response to norepinephrine (beta 1-, beta 2-, beta 3-, and alpha 2-AR agonist), isoprenaline (beta 1-, beta 2-, and beta 3-AR agonist), and CGP12177A (selective partial beta 3-AR agonist but beta 1- and beta 2-AR antagonist) together with post-receptor agents, forskolin and dibutyryl cyclic AMP. The female rats that had greater oxygen consumption showed higher UCP1 content, a higher multilocular arrangement, and both longer cristae and higher cristae dense mitochondria in BAT indicating heightened thermogenic capacity and activity; this picture is accompanied by a more sensitive beta 3-AR to norepinephrine signal (EC50 10-fold lower for CGP12177A) and a lower expression of alpha 2A-AR than male rats. Taken together, our results support the idea that the BAT hormonal environment could be involved in the control of different elements of lipolytic and thermogenic adrenergic pathways. Gender dimorphism is both at receptor (changing alpha 2A-AR density and beta 3-AR affinity) and post-receptor (modulating the links involved in the adrenergic signal transduction) levels. These changes in adrenergic control could be responsible, at least in part, both for the important mitochondrial recruitment differences and functional and morphological features of BAT in female rats under usual rodent housing temperatures.

* This work was supported in part by Dirección General de Enseñanza Superior e Investigación Científica Grants BFI2000-0988-C06-04 and BFI2000-0988-C06-06.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by a grant of the Universitat de les Illes Balears.

§ Supported by a grant of the Ministerio de Educación, Cultura y Deporte.

Supported by grant from the Comunitat Autònoma de les Illes Balears.

|| To whom correspondence should be addressed: Dra. Pilar Roca, Dept. Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears. Cra. Valldemossa km 7.5. E-07071-Palma de Mallorca, Spain. Tel.: 34-971-17-31-72; Fax: 34-971-173184; E-mail: pilar.roca@uib.es.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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