Herring Oil rich in long chain monounsaturated fatty acid (C22:1n-11) lowers Plasma Lipids and Modulates Fatty Acid Composition, Oxidation, and Inflammation in Rats

Camilla Nundal^1*Siri Tungland²Hege Gilbø Bakke³Pavol Bohov⁴Thomas Aquinas Aloysius⁴Arild Christian Rustan³Bodil Bjørndal⁵Aurora Brønstad⁶Jannike Øyen^6,7Suzanne Louise Robinson Brandt⁶Magne Olav Sydnes^2,8Ottar Kjell Nygård^10,9Simon N Dankel⁶Lise Madsen⁶Rolf Berge^10,4*

• ¹Western Norway University of Applied Sciences, Bergen, Norway
• ²Department of Chemistry, Bioscience, and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway
• ³Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Oslo, Norway
• ⁴Mito Biotech AS, Bergen, Norway
• ⁵Department of Sports, Food, and Natural Sciences, Western Norway University of Applied Sciences, Bergen, Norway
• ⁶Department of Clinical Medicine, University of Bergen, Bergen, Norway
• ⁷Norwegian Institute of Marine Research (IMR), Bergen, Hordaland, Norway
• ⁸Department of Chemistry, University of Bergen, Bergen, Norway
• ⁹Department of Heart Diseases, Haukeland University Hospital, Bergen, Norway
• ¹⁰Department of Clinical Science, University of Bergen, Bergen, Norway

Marine oils and fatty fish rich in long-chain n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (C20:5n-3, EPA), and docosahexaenoic acid (C22:6n-3, DHA), are reported to enhance fatty acid (FA) oxidation and reduce plasma triacylglycerol and cholesterol levels. In addition to n-3 PUFAs, herring oil contains long-chain monounsaturated fatty acids (MUFAs), including cetoleic acid (C22:1n-11). The aim of this study was to investigate the effect of consuming CETO3® oil, derived from herring, naturally rich in n-3 PUFAs and cetoleic acid, on plasma lipid levels, FA composition, mitochondrial oxidation, and inflammation in rats after 10 weeks of supplementation. CETO3® supplementation decreased plasma levels of total fat (-58%), triglycerides (-55%), total cholesterol (-41%), and LDL-cholesterol (-45%), while increasing the HDL/LDL-cholesterol ratio (46%). Additionally, CETO3® supplementation led to increased hepatic and plasma levels of long chain n-3, n-9, and n-11 MUFAs, including C22:1n-11, and decreased n-6 FA accumulation, suggesting an anti-inflammatory effect. The reduction in saturated long-chain FAs in both liver and plasma indicates increased hepatic peroxisomal and mitochondrial activity following herring oil consumption. Furthermore, increased oleic acid oxidation was observed in human myotubes in the presence of C20:1n-11 and C20:1n-9. In conclusion, supplementation with CETO3® oil, derived from herring, lowers plasma lipids, potentially mediated by peroxisomal and mitochondrial fatty acid oxidation, and appears safe, as hematological parameters and organ weights remained unaffected.