Emerging Insights into Very Long Chain Fatty Acids in Health and Disease.
Presented by:
Prof. Martin-Paul Agbaga
Synopsis
A LIPID MAPS Webinar hosted by Michael Gelb and presented by Prof. Martin-Paul Agbaga covering the following key points:
Very long chain fatty acids (VLC-FA)-containing lipids are critical for the function of the retina, brain, skin, and testes that express the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. We unequivocally demonstrated that ELOVL4 enzyme mediates biosynthesis of both very long chain polyunsaturated fatty acids (VLC-PUFAs) and VLC-saturated FA (VLC-SFAs), collectively referred to as VLC-FA (≥ C28) that play critical roles in ELOVL4-expressing issues. However, several ELOVL4 variants that affect VLC-FA biosynthesis cause blindness in autosomal dominant Stargardt-like macular dystrophy (STGD3), age-related spinocerebellar ataxia 34 (SCA34), and erythrokeratodermia variabilis (EKV), a scaly and dry skin lesions disorder. We seek to understand how the different ELOVL4 variants negatively impair VLC-FA biosynthesis to cause tissue-specific disorders. We have developed in vitro and in vivo models to test the hypothesis that the nature of the ELOVL4 variants affects VLC-FA biosynthesis to cause tissue-specific disease. Using these established models, we have shown that VLC-FAs are critical for the normal function of ELOVL4-expressing tissues and that ELOVL4 variants that cause decreased VLC-FA biosynthesis contribute to progressive vision loss in STGD3, cerebellar degeneration in SCA34 and EKV. Interestingly, recent studies have also shown that as we age, the levels of retinal VLC-PUFAs decrease even in people without ELOVL4 mutations. These findings underscore the need for a better understanding of the role of VLC-FA in health and disease so that we can translate our findings to identify potential therapeutics for treating VLC-FA deficiency disorders in humans.
Very long chain fatty acids (VLC-FA)-containing lipids are critical for the function of the retina, brain, skin, and testes that express the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. We unequivocally demonstrated that ELOVL4 enzyme mediates biosynthesis of both very long chain polyunsaturated fatty acids (VLC-PUFAs) and VLC-saturated FA (VLC-SFAs), collectively referred to as VLC-FA (≥ C28) that play critical roles in ELOVL4-expressing issues. However, several ELOVL4 variants that affect VLC-FA biosynthesis cause blindness in autosomal dominant Stargardt-like macular dystrophy (STGD3), age-related spinocerebellar ataxia 34 (SCA34), and erythrokeratodermia variabilis (EKV), a scaly and dry skin lesions disorder. We seek to understand how the different ELOVL4 variants negatively impair VLC-FA biosynthesis to cause tissue-specific disorders. We have developed in vitro and in vivo models to test the hypothesis that the nature of the ELOVL4 variants affects VLC-FA biosynthesis to cause tissue-specific disease. Using these established models, we have shown that VLC-FAs are critical for the normal function of ELOVL4-expressing tissues and that ELOVL4 variants that cause decreased VLC-FA biosynthesis contribute to progressive vision loss in STGD3, cerebellar degeneration in SCA34 and EKV. Interestingly, recent studies have also shown that as we age, the levels of retinal VLC-PUFAs decrease even in people without ELOVL4 mutations. These findings underscore the need for a better understanding of the role of VLC-FA in health and disease so that we can translate our findings to identify potential therapeutics for treating VLC-FA deficiency disorders in humans.
Watch Recording
About Prof. Martin-Paul Agbaga
Martin-Paul Agbaga, PhD is an Associate Professor of Cell Biology and Ophthalmology at the University of Oklahoma Health Sciences Center and the Dean McGee Eye Institute in Oklahoma City, Oklahoma, USA. He discovered the biological function of the ELOVL4 enzyme during his graduate studies under the mentorship of one of the leaders in retinal lipid metabolism, Professor Emeritus Robert E. Anderson, MD, PhD. Since then, Dr. Agbaga's research career has been focused on unraveling the critical role of VLC-FA-containing lipids in health and disease. He has generated in vitro and animal models that his team and his collaborators use to elucidate how different ELOVL4 variants affect VLC-FA biosynthesis to cause human tissue-specific disorders. His lecture will provide novel insights into the role of these unique fatty acids in health and disease that have not been previously appreciated.
November 26th, 2024
5pm GMT |
9am PST |
12pm EST
Prof. Martin-Paul Agbaga
https://dmei.org/research/vision-research/martin-paul-agbaga/