Low-level arsenite activates the transcription of genes involved in adipose differentiation

Abstract

In this study we analyzed gene expression in 3T3-F442A pre-adipocyte cells that differentiate in the presence of micro-molar arsenate concentration. Two concentrations of arsenite (As2O3, 0.25 micromol/L and 0.5 micromol/L) were applied for three days with and without insulin (170 nmol/L) and gene expressions were evaluated by quantitative RT-PCR. The genes included genes of oxidative-stress responses: heme-oxygenase-1 (HO1) and the hypoxia inducible factor 1a (HIF1alpha), genes of cell-cycle: c-jun and Kruppel like factor 5 (KLF5), and genes that play important roles in adipose determination: a peroxisome proliferator-activated receptor (PPARgamma) and a CCAAT/ enhancer binding protein (C/EBPalpha). Arsenite induced the expression of HO1, HIF1alpha, KLF5, PPARgamma and C/EBPalpha. These results suggest that under condition of oxidative stress arsenite induces genes that are required for adipose differentiation.

Arsenic Inhibits Myogenic Differentiation and Muscle Regeneration

“…Low-dose As 2 O 3 (0.25 and 0.5 μM) has been reported to activate the transcription of genes involved in adipose differentiation (Salazard et al 2004). In contrast, Wang et al (2005) reported that As 2 O 3 (3 μM) did not induce apoptosis but inhibited differentiation of preadipocyte 3T3-L1 cells.…”

Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis

“…The features of diabetes mellitus most commonly observed in arsenic-exposed individuals are similar to non-insulin-dependent diabetes mellitus or Type 2 diabetes [14]. Although the biological mechanisms responsible for arsenic-induced diabetes mellitus are largely unknown, recent evidence suggests that the trivalent arsenicals may suppress insulin-stimulated glucose uptake by interfering with mobilization of glucose transporters in adipose cells [36], as well as interfering with transcription factors involved in insulin-related gene expression [37]. …”

Essential role of KLF5 transcription factor in cell proliferation and differentiation and its implications for human diseases

“…In 3T3-L1 pre-adipocyte cells, which differentiate in the presence of micro-molar arsenic, arsenite treatment induces the expression of KLF5 [89]. A role of KLF5 in adipose differentiation was further demonstrated in a mouse model, where neonatal heterozygous KLF5 knockout mice exhibit a marked deficiency in white adipose tissue development [46].…”