N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models

Figure 6

Coordinated regulation of bile acid synthesis, transport, and metabolism by n-3 polyunsaturated fatty acids in human cell models for the liver, intestine, and kidney. Results from the present study indicate that n-3 polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids activate bile acid (BA) detoxification in the liver, intestine, and kidney. In liver (HepG2) cells, EPA and/or DHA dose- and time-dependently reduced mRNA levels of the rate limiting BA synthesizing CYP7A1 enzyme, while upregulating expression of the sinusoidal MRP2 and basolateral OSTα, MRP3, and MRP4 BA transporters. The SULT2A1 enzyme was also significantly upregulated. In Caco-2 and RPTEC, n-3 PUFAs exerted a similar stimulation of the BA detoxification enzymes encoded by MRP2 and MRP3 genes. These regulatory events lead to decreased BA synthesis and increased metabolism and elimination and, so, contribute to reducing systemic accumulation of BAs.