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

doi:10.1016/j.isci.2023.108411

Dietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function

iScience. 2023 Nov 7;26(12):108411. doi: 10.1016/j.isci.2023.108411. eCollection 2023 Dec 15.

Authors

Zhi-Hong Yang¹, Aruna Gorusupudi², Todd A Lydic³, Anupam K Mondal⁴, Seizo Sato⁵, Isao Yamazaki⁵, Hideaki Yamaguchi⁵, Jingrong Tang¹, Krishna Vamsi Rojulpote¹, Anna B Lin³, Hannah Decot³, Hannah Koch³, Daniel C Brock⁴, Ranganathan Arunkumar², Zhen-Dan Shi⁶, Zu-Xi Yu⁷, Milton Pryor¹, Julia F Kun¹, Rolf E Swenson⁶, Anand Swaroop⁴, Paul S Bernstein², Alan T Remaley¹

Affiliations

¹ Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
² Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, Salt Lake City, UT 84132, USA.
³ Department of Physiology, Collaborative Mass Spectrometry Core, Michigan State University, East Lansing, MI 48824, USA.
⁴ Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, NIH, Bethesda, MD 20892, USA.
⁵ Central Research Laboratory, Nissui Corporation, 1-32-3 Nanakuni, Hachioji, Tokyo 192-0991, Japan.
⁶ Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, MD 20892, USA.
⁷ Pathology Core, NHLBI, NIH, Bethesda, MD 20892, USA.

Abstract

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.

Keywords: Cell biology; Dietary supplement; Physiology.

Abstract

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