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. © 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH. Chemicals / CAS fenofibrate, 49562-28-9; fish oil, 308064-99-5, 8016-13-5; Fatty Acids, Omega-3; Fenofibrate; Fish Oils; Triglycerides