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ToxSci Advance Access originally published online on July 25, 2003
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Toxicological Sciences 75, 368-377 (2003)
Copyright © 2003 by the Society of Toxicology

IN VITRO TOXICOLOGY AND ALTERNATIVE TESTING

Effects of Inorganic HgCl2 on Adipogenesis

David M. Barnes*,{dagger},1, Paul R. Hanlon{dagger},{ddagger},2 and Emily A. Kircher*,{dagger},2

* Department of Animal Sciences, {dagger} Department of Molecular and Environmental Toxicology, and {ddagger} Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706

ABSTRACT

Mercury is a common pollutant that alters glucose metabolism in adipocytes; however, the effect of HgCl2 on differentiating adipocytes and their subsequent metabolic function is not well understood. Two adipocyte models, the 3T3-L1 and C3H10T1/2 (10T1/2) cell lines, were differentiated in the presence of HgCl2. To assess the amount of differentiation in a population, markers of differentiation (i.e., PPAR{gamma} and GLUT 4 expression and lipid accumulation) and functions of adipocytes (i.e., glucose transport and insulin-induced glucose transport) were measured. HgCl2 exposure significantly decreased the number of phenotypic adipocytes and PPAR{gamma} expression in both 3T3-L1 and 10T1/2 cells without effects on cell viability. GLUT 4 was significantly reduced by HgCl2 treatment in 10T1/2 but not 3T3-L1 cells. Exposure to HgCl2 during differentiation increased basal glucose uptake in a dose-dependent manner (up to 2.5-fold) and decreased insulin-induced glucose uptake in 3T3-L1 adipocytes. In contrast, HgCl2 had little effect on basal or insulin-induced glucose uptake in 10T1/2 cells, possibly due to their lower insulin responsiveness. We examined the effect of HgCl2 exposure on signaling event involved in differentiation of adipocytes and cellular stress, namely, the phosphorylation of ERK1/2 and JNK, respectively. HgCl2 exposure had no effect on ERK1/2 phosphorylation in either cell line, increased JNK phosphorylation in the 10T1/2, and had no effect on JNK phosphorylation in 3T3-L1 cells. These data indicate HgCl2 exposure can inhibit the differentiation of fibroblasts into adipocytes as well as influence signaling events and the subsequent metabolic activity of differentiated adipocytes.

Key Words: adipocyte; adipogenesis; mercury; differentiation; 3T3-L1; 10T1/2.


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