Dietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function
Zhi-Hong Yang,
Aruna Gorusupudi,
Todd A. Lydic,
Anupam K. Mondal,
Seizo Sato,
Isao Yamazaki,
Hideaki Yamaguchi,
Jingrong Tang,
Krishna Vamsi Rojulpote,
Anna B. Lin,
Hannah Decot,
Hannah Koch,
Daniel C. Brock,
Ranganathan Arunkumar,
Zhen-Dan Shi,
Zu-Xi Yu,
Milton Pryor,
Julia F. Kun,
Rolf E. Swenson,
Anand Swaroop,
Paul S. Bernstein,
Alan T. Remaley
Affiliations
Zhi-Hong Yang
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Aruna Gorusupudi
Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, Salt Lake City, UT 84132, USA
Todd A. Lydic
Department of Physiology, Collaborative Mass Spectrometry Core, Michigan State University, East Lansing, MI 48824, USA
Anupam K. Mondal
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, MD 20892, USA
Seizo Sato
Central Research Laboratory, Nissui Corporation, 1-32-3 Nanakuni, Hachioji, Tokyo 192-0991, Japan
Isao Yamazaki
Central Research Laboratory, Nissui Corporation, 1-32-3 Nanakuni, Hachioji, Tokyo 192-0991, Japan
Hideaki Yamaguchi
Central Research Laboratory, Nissui Corporation, 1-32-3 Nanakuni, Hachioji, Tokyo 192-0991, Japan
Jingrong Tang
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Krishna Vamsi Rojulpote
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Anna B. Lin
Department of Physiology, Collaborative Mass Spectrometry Core, Michigan State University, East Lansing, MI 48824, USA
Hannah Decot
Department of Physiology, Collaborative Mass Spectrometry Core, Michigan State University, East Lansing, MI 48824, USA
Hannah Koch
Department of Physiology, Collaborative Mass Spectrometry Core, Michigan State University, East Lansing, MI 48824, USA
Daniel C. Brock
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, MD 20892, USA
Ranganathan Arunkumar
Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, Salt Lake City, UT 84132, USA
Zhen-Dan Shi
Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, MD 20892, USA
Zu-Xi Yu
Pathology Core, NHLBI, NIH, Bethesda, MD 20892, USA
Milton Pryor
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Julia F. Kun
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Rolf E. Swenson
Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, MD 20892, USA
Anand Swaroop
Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, MD 20892, USA
Paul S. Bernstein
Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, Salt Lake City, UT 84132, USA; Corresponding author
Alan T. Remaley
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Corresponding author
Summary: Very-long-chain polyunsaturated fatty acids (VLCPUFAs; C24-38) constitute a unique class of PUFA that have important biological roles, but the lack of a suitable dietary source has limited research in this field. We produced an n-3 C24-28-rich VLCPUFA-oil concentrated from fish oil to study its bioavailability and physiological functions in C57BL/6J mice. The serum and retinal C24:5 levels increased significantly compared to control after a single-dose gavage, and VLCPUFAs were incorporated into the liver, brain, and eyes after 8-week supplementation. Dietary VLCPUFAs resulted in favorable cardiometabolic changes, and improved electroretinography responses and visual performance. VLCPUFA supplementation changed the expression of genes involved in PPAR signaling pathways. Further in vitro studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 are potent agonists for PPARs. The multiple potential beneficial effects of fish oil-derived VLCPUFAs on cardiometabolic risk and eye health in mice support future efforts to develop VLCPUFA-oil into a supplemental therapy.
