The role of N-acyl-ethanolamine biosynthetic enzymes in the attenuation of cardiometabolic diseases.
Presented by:
Dr. Sean S. Davies
Synopsis
A LIPID MAPS webinar hosted by Maria Fedorova with presenter Dr Sean S. Davies covering the following key points:
1. Individual N-acyl-ethanolamine (NAE) species vary in their potency at key receptors, and therefore have unique as well as overlapping biological activities. Pharmacologic administration of palmityolethanolamide (PEA) or oleoylethanolamide (OEA) inhibits development of cardiometabolic diseases.
2. Multiple enzymes potentially contribute to NAE biosynthesis, and the relationship between these enzymes, and how their activity is regulated remains an area of active investigation.
3. N-acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is a key component of NAE biosynthesis and recent evidence suggests that its loss worsens cardiometabolic diseases.
4. NAPE-PLD and NAEs appear to play an important role in regulating macrophage polarity and function, particularly their capacity to carry out efferocytosis. Impaired efferocytosis is a critical factor in atherosclerosis and impaired wound healing in diabetics. NAPE-PLD activators enhance efferocytosis by cultured macrophages and may therefore have therapeutic value.
1. Individual N-acyl-ethanolamine (NAE) species vary in their potency at key receptors, and therefore have unique as well as overlapping biological activities. Pharmacologic administration of palmityolethanolamide (PEA) or oleoylethanolamide (OEA) inhibits development of cardiometabolic diseases.
2. Multiple enzymes potentially contribute to NAE biosynthesis, and the relationship between these enzymes, and how their activity is regulated remains an area of active investigation.
3. N-acyl-phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) is a key component of NAE biosynthesis and recent evidence suggests that its loss worsens cardiometabolic diseases.
4. NAPE-PLD and NAEs appear to play an important role in regulating macrophage polarity and function, particularly their capacity to carry out efferocytosis. Impaired efferocytosis is a critical factor in atherosclerosis and impaired wound healing in diabetics. NAPE-PLD activators enhance efferocytosis by cultured macrophages and may therefore have therapeutic value.
Watch Recording
About Dr. Sean S. Davies
Bioblurb:
Dr. Sean S. Davies is an Associate Professor in the Department of Pharmacology and the Division of Clinical Pharmacology at Vanderbilt University. He did his PhD studies with Dr. Thomas McIntyre at the University of Utah, examining cell signaling pathways induced by oxidized phospholipid. He then did post-doctoral studies with Dr. L. Jackson Roberts at Vanderbilt University, studying the role of reactive dicarbonyls generated by lipid peroxidation, especially isolevuglandins, in chronic diseases. During this time, he identified 2-aminomethylphenols as effective small molecule scavengers of these lipid dicarbonyls and subsequent studies have demonstrated the efficacy of these scavengers in animal models of chronic diseases including atherosclerosis. In 2007, he received one of the inaugural NIH director’s New Innovator Awards. This funding allowed him to demonstrate that incorporating Nissle 1917 (a probiotic bacterial strain) bioengineered to generate high levels of N-acyl-phosphatidylethanolamines (the precursor to N-acylethanolamines) into host gut microbiota could be used to treat cardiometabolic diseases. More recent studies in his lab have focused on understanding how the biosynthesis of N-acylethanolamines (NAEs) is regulated in vertebrates, the role of NAEs in regulating metabolism and inflammation, and the potential of small molecule activators of NAPE-PLD to ameliorate cardiometabolic diseases.
September 24th, 2024
5pm BST |
9am PDT |
12pm EDT
Dr. Sean S. Davies