Different effects of trans -10, cis -12 conjugated linoleic acid (10,12-CLA) and of its oxidation product 10,13-epoxy-10,12-octadecadienoic acid (10,12-FFA) on the proteome of human intestinal Caco-2 cells

Conjugated linoleic acids (CLAs) have different functional effects on human health. They are supposed to contribute to the reduction of body fat mass and to the increase of lean muscle mass. Therefore, CLAs are already available as functional food in the USA, and the same is planned in the EU. CLAs are classified as "novel foods" in the EU, and a premarketing risk assessment of CLAs is a mandatory part of the novel food approval. For a reliable risk assessment of CLAs it is necessary also to focus on the CLA metabolites furan fatty acids (FFAs), which can arise from autoxidation of CLAs and which may have some properties of toxicological relevance. Up to now, hardly anything is known about the effects of FFAs on humans.To analyse the molecular effects of trans -10, cis- 12-CLA (10,12-CLA) and of its oxidation product 10,13-epoxy-10,12-octadecadienoic acid (10,12-FFA) in more detail, we conducted a proteomic study based on two-dimensional gel electrophoresis and mass spectroscopy by using the human intestinal cell line Caco-2. We detected 68 proteins that were differentially regulated by at least 1.5-fold upon incubation of the cells with 10,12-CLA, and incubation of the cells with 10,12-FFA yielded 61 differentially regulated proteins. A subsequent pathway analysis revealed that various molecular and cellular functions such as cellular development, cell cycle, drug metabolism and endocrine system development and function were affected by 10,12-CLA. In case of 10,12-FFA, metabolic pathways including amino acid and nucleotide metabolism were down-regulated in the cells. From these results we conclude that 10,12-CLA affects numerous cellular regulatory and metabolic pathways, whereas 10,12-FFA predominantly down-regulates cellular metabolic activity thereby driving the cells into a state of rest.