Transcription profiling of cadmium-exposed livers reveals alteration of lipid metabolism and predisposition to hepatic steatosis

1. Cadmium (Cd) is a ubiquitous environmental toxicant that can cause liver steatosis and nonalcoholic fatty liver disease (NAFLD) on long-term exposure. 2. Sixteen Sprague Dawley rats were randomly divided into two groups, and were administered normal saline and 5 mg/(kg center dot d) cadmium chloride by gavage. In vitro, BRL3A cells, a rat normal liver cell line, were treated with different concentrations of Cd to verify the sequencing results. 3. The RNA-seq revealed 146 upregulated genes and 127 downregulated genes in the Cd intervention group. The key genes of lipid metabolism were significantly overexpressed, such as Cyp1a1 and Pla2g2d. The GO enrichment analysis showed that the 'sterol biosynthetic process' was the most obvious difference. The KEGG analysis showed that six of the top 10 differential pathways were related to lipid metabolism. The expression of the essential genes in BRL3A was consistent with the sequencing results. The protein-protein interaction (PPI) yielded that Cyp1a1 is in the central region of the differentially expressed gene network. 4. The chronic Cd exposure is still an important environmental health problem with a probable tendency to cause NAFLD. It may possibly act by affecting the lipid metabolism in the liver, especially the synthesis and decomposition of unsaturated fatty acids.