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1 Trace Element and Gene Expression Group and 2 Molecular Physiology Group, Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB; 3 Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom; and 4 Department of Biochemistry, University of Tasmania, Hobart, Tasmania 7001, Australia
Metallothionein (MT) is thought to have
an antioxidant function and is strongly expressed during activation of
thermogenesis and increased oxidative stress in brown adipose tissue
(BAT). Localization and regulation of MT expression in BAT was
therefore investigated in rats and mice. Immunohistochemical analysis
of BAT from rats exposed to 4°C for 24 h showed that MT and
uncoupling protein 1 (UCP1) were coexpressed in differentiated
adipocytes, and both cytoplasmic and nuclear localization of MT was
observed. Cold induction of MT-1 expression in BAT was also observed in mice. Administration of norepinephrine to rats and isoproterenol to
mice stimulated MT and UCP1 expression in BAT, implying a
sympathetically mediated pathway for MT induction. In mice, zinc, and
particularly dexamethasone, induced MT-2 expression in BAT and liver.
Surprisingly, zinc also induced UCP1 in BAT, suggesting that elevated
zinc may induce thermogenesis. We conclude that expression of MT in
mature brown adipocytes upon 
-adrenoceptor activation is consistent with a role in protecting against physiological oxidative stress or in
facilitating the mobilization or utilization of energy reserves.
uncoupling protein 1; dexamethasone; cold exposure; thermogenesis; oxidative stress
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