Subchronic cadmium exposure upregulates the mRNA level of genes associated to hepatic lipid metabolism in adult female CD1 mice

Abstract

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in humans and shows adverse effects on health. Accumulating evidence reveals that environmental Cd exposure is associated with hepatic lipid accumulation and metabolic alterations in adult male mice. However, whether Cd exposure induces hepatic lipid accumulation and metabolic alterations in female mice remains poorly understood. In the present study, we aimed to investigate the effects of Cd exposure on insulin resistance, hepatic lipid accumulation and associated metabolic pathways. Female CD1 mice were administrated with CdCl (10 and 100 mg l ) by drinking water. We found that Cd exposure did not induce obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in the Cd-100 mg l group presented a significant reduction of the glucose area under the curve during the glucose tolerance test. However, there was a significant elevation in the mRNA level of Fasn and Scd-1, which were critical genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two genes for hepatic fatty acid uptake were upregulated in Cd-treated mice. Of interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in Cd-treated mice. Collectively, our results suggest that Cd exposure upregulated mRNA level of genes related to hepatic lipid metabolism although there was no insulin resistance and hepatic lipid accumulation shown in the present study.

Chronic cadmium exposure induced hepatic cellular stress and inflammation in aged female mice

“…The results were inconsistent with the study in which the subacute Cd exposure induced lipid accumulation in adult male mice(Go et al, 2015). There may be gender differences in the effects of Cd on the liver toxicity that has been discussed in our previous study(Zhang et al, 2018). However, the results were consistent with our previous study(Zhang et al, 2018), in which no significant lipid accumulation was observed after subchronic Cd exposure, although the mRNA level of genes associated to hepatic lipid metabolism was elevated in adult female mice.…”

“…There may be gender differences in the effects of Cd on the liver toxicity that has been discussed in our previous study(Zhang et al, 2018). However, the results were consistent with our previous study(Zhang et al, 2018), in which no significant lipid accumulation was observed after subchronic Cd exposure, although the mRNA level of genes associated to hepatic lipid metabolism was elevated in adult female mice. Mt, the metal-binding proteins and the most responsive proteins to Cd exposure, are small cysteine-…”

Review of polyphenol‐rich products as potential protective and therapeutic factors against cadmium hepatotoxicity

“…This element disrupts the adhesion of cells by displacement of Ca from E‐cadherin (transmembrane glycoproteins responsible for the proper adhesion of cells in a tissue) leading to activation of β‐catenins (signaling molecules) and an enhancement of cell proliferation (Bruscalupi, Massimi, Devirgiliis, & Leoni, ). Cd may affect gene expression and stimulate carcinogenesis by proto‐oncogene induction, inhibition of DNA methylation and disruption of cell signaling pathways (Chen et al, ; Fabbri et al, ; Tang et al, ; Zhang et al, ). It has been revealed in many experimental models that this element influences hepatocyte apoptosis and necrosis under conditions of in vivo and in vitro exposure (Chen et al, ; Mężyńska et al, ; Rogalska et al, ; Skipper et al, ).…”

“…an enhancement of cell proliferation (Bruscalupi, Massimi, Devirgiliis, & Leoni, 2009). Cd may affect gene expression and stimulate carcinogenesis by proto-oncogene induction, inhibition of DNA methylation and disruption of cell signaling pathways (Chen et al, 2014;Fabbri et al, 2012;Tang et al, 2013;Zhang et al, 2018). It has been revealed in many experimental models that this element influences hepatocyte apoptosis and necrosis under conditions of in vivo and in vitro exposure (Chen et al, 2014;Mężyńska et al, 2016;Rogalska et al, 2011;Skipper et al, 2016).…”

Time‐dependent response of A549 cells upon exposure to cadmium

“…ions such as, zinc (Zn), copper (Cu), manganese (Mn) and iron bound to the enzymes and other biomolecules, interfere with the homeostasis of essential metals, trigger reactive oxygen species formation and disrupt the cellular function of biologically important molecules (Adiele, Stevens, & Kamunde, 2012;Kitamura & Hiramatsu, 2010;Zhang et al, 2018). Cells respond to Cd exposure with multi-strategies.…”