The gene encoding metallothionein, a low mol. wt. metal binding and stress response
protein, is expressed in white adipose tissue. In the present study, metallothionein
(MT-1) gene expression and factors regulating metallothionein production have been
examined in adipocytes induced to differentiate from fibroblastic preadipocytes in
primary cell culture. On the induction of differentiation, the metallothionein-1 gene
was strongly expressed in the cells and metallothionein released into the medium.
A peak in metallothionein-1 mRNA level and metallothionein secretion occurred at 2
and 10 days post-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 early marker
of adipocyte differentiation. The addition of the glucocorticoid, dexamethasone, led
to a substantial increase in metallothionein-1 mRNA in the cells and metallothionein
secretion. Insulin and leptin also stimulated metallothionein production, although
the effect was small. Neither noradrenaline nor the β3-adrenoceptor agonist, BRL 37
344, altered metallothionein release but forskolin and bromo-cAMP were stimulatory,
markedly increasing both metallothionein-1 level and metallothionein secretion. It
is suggested that metallothionein is a novel secretory product of the differentiated
white adipocyte and that its production is regulated particularly by glucocorticoids
and through a cAMP-dependent pathway.
Key words
Antioxidant - cAMP - Catecholamines - Glucocorticoids - Leptin - White Adipose Tissue
