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J. Biol. Chem., Vol. 275, Issue 33, 25073-25081, August 18, 2000
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From the Wenner-Gren Institute, The Arrhenius Laboratories F3,
Stockholm University, SE-106 91 Stockholm, Sweden
To examine the thermogenic significance of the
classical uncoupling protein-1 (UCP1), the thermogenic potential of
brown adipocytes isolated from UCP1-ablated mice was investigated.
Ucp1(
Thermogenic Responses in Brown Fat Cells Are Fully
UCP1-dependent
UCP2 OR UCP3 DO NOT SUBSTITUTE FOR UCP1 IN ADRENERGICALLY OR
FATTY ACID-INDUCED THERMOGENESIS*
,
/) cells had a basal metabolic rate identical to
wild-type; the mitochondria within them were coupled to the same
degree. The response to norepinephrine in wild-type cells was robust
(
10-fold increase in thermogenesis); Ucp1(/) cells only responded 3% of
this. Ucp1(/) cells were as potent as
wild-type in norepinephrine-induced cAMP accumulation and lipolysis and
had a similar mitochondrial respiratory complement. In wild-type cells,
fatty acids induced a thermogenic response similar to norepinephrine,
but fatty acids (and retinoate) were practically without effect in
Ucp1(/) cells. It is concluded that no
other adrenergically induced thermogenic mechanism exists in brown
adipocytes except that mediated by UCP1 and that entopic expression of
UCP1 does not lead to overt innate uncoupling, and it is suggested that
fatty acids are transformed to an intracellular physiological activator
of UCP1. High expression of UCP2 and UCP3 in the tissue was not
associated with an overt innate highly uncoupled state of mitochondria
within the cells, nor with an ability of norepinephrine or endo- or
exogenous fatty acids to induce uncoupled respiration in the cells.
Thus, UCP1 remains the only physiologically potent thermogenic
uncoupling protein in these cells.
*
This work was supported by a grant (to B. C. and
J. N.) and a postdoctoral fellowship (to A. M.) from the
Swedish Natural Science Research Council.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.
Present address: Dept. of Medicine, University of Queensland,
Royal Brisbane Hospital, Herston, QLD 4029, Australia.
§
To whom correspondence should be addressed: The
Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm
University, SE-106 91 Stockholm, Sweden. Tel.: 46 8 164120; Fax: 46 8 156756; E-mail: barbara.cannon@wgi.su.se.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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