Triglyceride lowering by omega-3 fatty acids: a mechanism mediated by N-acyl taurines

Abstract

Interest in omega-3 fatty acids (colloquially known as fish oils) to lower residual cardiovascular risk in statin-treated patients has increased markedly in the wake of recent cardiovascular outcome trials. The triglyceride-lowering effects of omega-3 fatty acids are generally thought to occur by reduced hepatic VLDL production. In this issue of the JCI, Grevengoed et al. used mouse models and human plasma samples to reveal an additional mechanism whereby these polyunsaturated fatty acids can lower plasma triglycerides. Their findings indicate that omega-3 fatty acid-derived N-acyl taurines (NATs) greatly accumulate in bile and also in plasma following omega-3 supplementation. The authors further show that one of these NATs (C22:6 NAT) inhibited intestinal triglyceride hydrolysis and lipid absorption, which resulted in lower plasma triglycerides and protection against hepatic triacylglycerol accumulation in mice fed a high-fat diet. The findings open a potential avenue for triglyceride lowering by omega-3 fatty acids conjugated to taurine.

Figure 1. Model for omega-3 fatty acid cardioprotection.

The omega-3 fatty acids EPA (C20:5) and DHA (C22:6) affect processes that are likely involved in protection against CVD, although the cardioprotective effects of EPA and DHA are intensely debated, given the results of recent cardiovascular outcome trials. Individual omega-3 fatty acids may have specific effects; their protective effects are possibly related to reduced plasma triglycerides through reduced hepatic lipogenesis and VLDL production, increased TRL (chylomicron) lipolysis, increased antiinflammatory and proresolving lipid mediators, and reduced thrombosis. Grevengoed et al. (19) showed that biliary C22:6 NAT prevents intestinal triglyceride absorption, providing an additional mechanism for how DHA lowers plasma and liver triglycerides.