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J Biol Chem, Vol. 274, Issue 33, 23368-23377, August 13, 1999
Rat Peroxisome Proliferator-activated Receptors and Brown Adipose
Tissue Function during Cold Acclimatization
Hebe M.
Guardiola-Diaz ,
Stefan
Rehnmark¶,
Nobuteru
Usuda**,
Tatjana
Albrektsen ,
Dorothee
Feltkamp ,
Jan-Åke
Gustafsson §§, and
Stefan E. H.
Alexson¶¶
From the Center for Biotechnology, the
§§ Department of Medical Nutrition, and the
¶¶ Division of Clinical Chemistry, Huddinge University
Hospital, Karolinska Institute, S-141 86, Huddinge, Sweden, the
¶ Department of Metabolic Research, Wenner-Gren Institute,
University of Stockholm, S-106 91, Stockholm, Sweden, and the
** Department of Anatomy and Cell Biology, Shinshu University School of
Medicine, 3-1-1 Asahi, Matsumoto 390, Japan
Brown adipose tissue (BAT) hyperplasia is a
fundamental physiological response to cold; it involves an acute phase
of mitotic cell growth followed by a prolonged differentiation phase.
Peroxisome proliferator-activated receptors (PPARs) are key regulators
of fatty acid metabolism and adipocyte differentiation and may
therefore mediate important metabolic changes during non-shivering
thermogenesis. In the present study we have investigated PPAR mRNA
expression in relation to peroxisome proliferation in rat BAT during
cold acclimatization. By immunoelectron microscopy we show that the number of peroxisomes per cytoplasmic volume and acyl-CoA oxidase immunolabeling density remained constant (thus increasing in parallel with tissue mass and cell number) during the initial proliferative phase and the acute thermogenic response but increased after 14 days of
cold exposure, correlating with terminal differentiation of BAT. A
pronounced decrease in BAT PPAR and PPAR mRNA levels was
found within hours of exposure to cold, which was reversed after 14 days, suggesting a role for either or both of these subtypes in the
proliferation and induction of peroxisomes and peroxisomal -oxidation enzymes. In contrast, PPAR mRNA levels increased progressively during cold exposure. Transactivation assays in HIB 1B
and HEK-293 cells demonstrated an adrenergic stimulation of peroxisome
proliferator response element reporter activity via PPAR, establishing
a role for these nuclear receptors in hormonal regulation of gene
transcription in BAT.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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