An integrated multi-omics analysis of the effects of the food processing-induced contaminant 2-monochloropropane-1,3-diol (2-MCPD) in rat heart

Abstract

Many foods including edible oils contain 2-monochloropropane-1,3-diol (2-MCPD), a processing-induced chemical contaminant. Cardiotoxic effects have been shown to result from oral 2-MCPD exposure in rodents, but the underlying mechanisms of action remain poorly understood. We undertook a comprehensive multi-omics approach to assess changes at the transcriptomic, proteomic, and oxylipin levels in heart tissues from male F344 rats that were exposed to 0 or 40 mg/kg BW/day of 2-MCPD in the diet for 90 days, in a regulatory compliant rodent bioassay. Heart tissues were collected for RNA sequencing, quantitative PCR analysis, proteomic analysis via two-dimensional gel electrophoresis and mass spectrometry, and targeted lipidomic profiling by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Transcriptomic and proteomic data analyses revealed upregulation of immune/inflammatory response processes and downregulation of energy metabolism and cardiac structure and functions. Among differentially expressed gene-protein pairs, coronin-1A, a key leukocyte-regulating protein, emerged as markedly up-regulated. Oxylipin profiling highlighted a selective suppression of docosahexaenoic acid-derived metabolites, suggesting a disruption in cardioprotective lipid pathways. These findings suggest that 2-MCPD disrupts homeostasis through inflammatory activation and suppression of metabolic and cardiac function. This research provides insights into 2-MCPD's cardiotoxicity, emphasizing the need for further studies to support hazard characterization.

Keywords: 2-MCPD; Cardiotoxicity; Multi-omics; Oxylipin; Proteome; Transcriptome.

Fig. 1

Comparison of rat heart transcriptomic profiles between control and treatment. a PCA scores plot of rat heart transcripts. Color overlaid by group. Ellipses illustrate 95% confidence intervals. b Volcano plot of rat heart transcripts. Dark blue, LFC < -1 and FDR < 0.05; light blue, LFC < -0.5 and P < 0.05; gray, no change; pink, LFC > 0.5 and P < 0.05; red, LFC > 1 and FDR < 0.05. c Correlation plot of sample DEG profiles. Colors represent Pearson correlation coefficients

Fig. 2

Gene set enrichment analysis of Gene Ontology biological processes. a Positively enriched GO terms by top FDR. b Negatively enriched GO terms by top FDR. c Network of enriched processes with nodes as GO terms. Edge length inversely related to the number of similar genes in the connected sets. d Enriched cardiac processes by FDR. All processes altered were suppressed

Fig. 3

Comparison of rat heart proteomic profiles between control and treatment. a PCA scores plot of rat heart proteins. Color overlaid by group. Ellipses illustrate 95% confidence intervals. b Volcano plot of rat heart proteins. Dark blue, LFC < -1 and FDR < 0.05; light blue, LFC < -0.5 and P < 0.05; gray, no change; pink, LFC > 0.5 and P < 0.05; red, LFC > 1 and FDR < 0.05. c Correlation plot of sample DEG profiles. Colors represent Pearson correlation coefficients

Fig. 4

Matched rat heart gene–protein pairs differentially expressed with 2-MCPD treatment. a Scatter plot of matched significantly altered (P < 0.05) genes and proteins by expression in LFC. Red, gene and protein expression |LFC|> 1 and FDR < 0.05; pink, gene and protein expression |LFC|> 0.5 and FDR < 0.1; gray, gene and/or protein not differentially expressed. b DEG-DEP expression values

Fig. 5

Comparison of rat heart oxylipin profiles between control and treatment. a PCA scores plot of rat heart oxylipins. Color overlaid by group. Ellipses illustrate 95% confidence intervals. b Volcano plot comparison of rat heart oxylipins between control and treatment. Dark blue, LFC < -1 and FDR < 0.05; light blue, LFC < − 0.5 and P < 0.05; gray, no change

Fig. 6

DHA oxylipin synthesis via LOX and CYP ω-hydrolase pathways. Quantified oxylipins colored in shades of blue if differentially expressed or gray if not altered. White, Oxylipins < LOQ; khaki, enzymes and non-oxylipin lipids