Comparative Analysis of the Effects of Fish Oil and Fenofibrate on Plasma Metabolomic Profiles in Overweight and Obese Individuals

SCOPE: The drug fenofibrate and dietary fish oils can effectively lower circulating triglyceride (TG) concentrations. However, a detailed comparative analysis of the effects on the plasma metabolome is missing. METHODS AND RESULTS: Twenty overweight and obese subjects participate in a double‐blind, cross‐over intervention trial and receive in a random order 3.7 g day(‐1) n‐3 fatty acids, 200 mg fenofibrate, or placebo treatment for 6 weeks. Four hundred twenty plasma metabolites are measured via gas chromatography–mass spectrometry (GC‐MS) and liquid chromatography–mass spectrometry (LC‐MS). Among the treatments, 237 metabolites are significantly different, of which 22 metabolites change in the same direction by fish oil and fenofibrate, including a decrease in several saturated TG‐species. Fenofibrate additionally changes 33 metabolites, including a decrease in total cholesterol, and total lysophosphatidylcholine (LPC), whereas 54 metabolites are changed by fish oil, including an increase in unsaturated TG‐, LPC‐, phosphatidylcholine‐, and cholesterol ester‐species. All q < 0.05. CONCLUSION: Fenofibrate and fish oil reduce several saturated TG‐species markedly. These reductions have been associated with a decreased risk for developing cardiovascular disease (CVD). Interestingly, fish oil consumption increases several unsaturated lipid species, which have also been associated with a reduced CVD risk. Altogether, this points towards the power of fish oil to change the plasma lipid metabolome in a potentially beneficial way.