P. Trayhurn et al., Regulation of metallothionein gene expression and secretion in rat adipocytes differentiated from preadipocytes in primary culture, HORMONE MET, 32(11-12), 2000, pp. 542-547
The gene encoding metallothionein, a low mel. wt. metal binding and stress
response protein, is expressed in white adipose tissue. In the present stud
y, metallothionein (MT-1) gene expression and factors regulating metallothi
onein production have been examined in adipocytes induced to differentiate
from fibroblastic preadipocytes in primary cell culture. On the induction o
f differentiation, the metallothionein-1 gene was strongly expressed in the
cells and metallothionein released into the medium. A peak in metallothion
ein-1 mRNA level and metallothionein secretion occurred at 2 and 10 days po
st-differentiation, respectively, with a decrease in protein release after
this time. The metallothionein-1 gene was expressed in the adipocytes prior
to the adipsin and lipoprotein lipase genes, suggesting that it is an earl
y marker of adipocyte differentiation. The addition of the glucocorticoid.
dexamethasone, led to a substantial increase in metallothionein-1 mRNA in t
he cells and metallothionein secretion. Insulin and leptin also stimulated
metallothionein production, although the effect was small. Neither noradren
aline nor the beta3-adrenoceptor agonist, BRL 37 344, altered metallothione
in release but forskolin and bromo-cAMP were stimulatory, markedly increasi
ng both metallothionein-1 level and metallothionein secretion. It is sugges
ted that metallothionein is a novel secretory product of the differentiated
white adipocyte and that its production is regulated particularly by gluco
corticoids and through a cAMP-dependent pathway.