Cadmium modulates adipocyte functions in metallothionein-null mice

Abstract

Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT(-/-)) mice, which cannot form atoxic Cd-MT complexes and are used for evaluating Cd as free ions, and wild type (MT(+/+)) mice. Cd administration more significantly reduced the adipocyte size of MT(-/-) mice than that of MT(+/+) mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT(-/-) mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes.

Keywords: Acaca; Adipokine; Adipose tissue; BMI; C/EBP; CCAAT/enhancer binding protein (C/EBP); CHD; Cadmium; Ccl2; Cd; FFA; Fasn; HFD; Il6; Lipe; MT; Mest; Metallothionein; PAI-1; Plin1; Pnpla2; Pparγ2; Retn; T2D; TG; Tnf-α; WAT; acetyl-Coenzyme A carboxylase alpha; body mass index; cadmium; chemokine (C–C motif) ligand 2 (MCP-1); coronary heart disease; fatty acid synthase; free fatty acids; high-fat diet; interleukin 6; lipase, hormone sensitive (HLS); mesoderm specific transcript; metallothionein; patatin-like phospholipase domain containing 2 (ATGL); perilipin 1; peroxisome proliferator activated receptor gamma 2; plasminogen activator inhibitor-1; resistin; triglyceride; tumor necrosis factor-α; type 2 diabetes; white adipose tissue.