[acute]er-adrenergic agonist induces a functionally active
uncoupling protein in fat and slow-twitch muscle fibers.
Yoshida, Toshihide, Tsunekazu Umekawa, Kenzo Kumamoto, Naoki Sakane,
Akinori Kogure, Motoharu Kondo, Yasuo Wakabayashi, Teruo Kawada,
Itsuro Nagase, and Masayuki Saito.
First Department of Internal Medicine and Department of
Biochemistry, Kyoto Prefectural University of Medicine, Kyoto 602,
Department of Anatomy, Meiji College of Oriental Medicine, Hiyoshi,
Kyoto 629-03, Department of Food Science and Technology, Faculty of
Agriculture, Kyoto University, Kyoto 602, and Department of
Biomedical Sciences, Laboratory of Biochemistry, Graduate School of
Veterinary Medicine, Hokkaido University, Sapporo 060, Japan
APStracts 4:0268E, 1997.
The mitochondrial uncoupling protein (UCP) has usually been found only
in brown adipose tissue. We recently observed that a chronic
administration of the [acute]eR-adrenergic agonist CL316,243 (CL)
induced the ectopic expression of UCP in white fat and skeletal
muscle in genetic obese yellow KK mice. The aim of the present study
was to examine whether UCP could be induced in non-genetic obese
animals produced by neonatal injections of monosodium-L-glutamate
(MSG). The daily subcutaneous injection of CL (0.1 mg/kg) to MSG
-induced obese mice for 2 weeks caused significant reductions of body
weight (15%) and white fat pad weight (58%). Northern and Western
blot analyses showed that CL induced significant expressions of UCP
in the white fat and muscle, as well as in brown fat.
Immunohistochemical observations revealed that the UCP stains in
white fat were localized on multilocular cells and that those in
muscle were localized on slow-twitch fibers rich in mitochondria.
Immunoelectron microscopy confirmed the mitochondrial localization of
UCP in the myocytes. The guanosine 5'-diphosphate (GDP) binding to
mitochondria in brown fat doubled after the CL treatment. Moreover,
significant GDP binding was detected in the white fat and muscle of
the CL-treated mice, at about the one-fourth and one-thirteenth the
activity of brown fat, respectively, suggesting that the ectopically
expressed UCP is functionally active. We concluded that the
[acute]eR-adrenergic agonist CL can induce functionally active UCP in
white fat and slow-twitch muscle fibers of obese mice.
Received 25 June 1997; accepted in final form 12 November 1997.
APS Manuscript Number E299-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997