ADVERTORIAL
The role of plasmalogens in chronic disease management
by Laura Dwyer | BHSc ( Naturopathy )
Snapshot
• Plasmalogens are essential for many biological systems that serve as molecular targets for oxidative stress and play crucial roles in signalling , inflammation , and immune responses .
• Consequently , lipidomic profiling has identified reduced plasmalogens in patients with chronic inflammatory diseases , including obesity , atherosclerosis , hypertension , metabolic syndrome , coronary artery disease , type 2 diabetes , hypertension , steatohepatitis , multiple sclerosis , systemic lupus erythematosus , inflammatory bowel disease and respiratory illnesses .
• Changes in plasmalogen levels in several conditions where inflammation plays a key role suggests restoring these lipids may ameliorate certain pathological hallmarks and provides a novel therapy for disease management .
Plasmalogens are amongst the most common glycerophospholipids and comprise approximately 20 % of total membrane phospholipids . By virtue of their vinyl-ether bond and enrichment of polyunsaturated fatty acid moieties , plasmalogens provide unique membrane structural attributes , modulate lipidassociated signalling pathways , and protect nucleic acids and lipids from oxidative damage . 1 Despite their wide distribution within the brain , heart , immune cells , and muscles , 2 plasmalogens have received very little attention compared with many other lipid classes . While a significant body of research supports their use in age-related neurodegenerative diseases , plasmalogens have begun attracting attention for their potential role in cardiometabolic , autoimmune and respiratory conditions .
Cardiometabolic diseases Imbalances in lipid signalling pathways are involved in the inflammatory response and contribute to the progression of various cardiometabolic diseases . 2 Likewise , mitochondrial dysfunction may increase oxidative stress , which activates inflammasomes and results in widespread chronic inflammation . 3 The vinyl-ether bond of plasmalogens has been shown to possess scavenging activity and thus may act as endogenous antioxidants in defending cell membranes and lipoproteins from free radical species , which are associated with these cardiometabolic pathological states . 4 Lipidomic profiling of human cohorts has identified a negative association between plasmalogens and obesity , 5 atherosclerosis , 6 hypertension , 7 metabolic syndrome , 8 coronary artery disease , 9 , 10 type 2 diabetes 8 and non-alcoholic steatohepatitis , 11 , 12 supporting their potential role in the management and prevention of these diseases . 1 Moreover , as plasmalogen-deficient cells have been shown to exhibit lower esterified cholesterol and have increased levels of free and total cholesterol 13 , 14 future research may identify plasmalogens as an alternative or adjunct to statin therapy in achieving cholesterol homeostasis . 15
Autoimmune diseases Lipid metabolism and signalling play an essential role in inflammation and oxidation with significant implications for certain autoimmune diseases , including inflammatory bowel diseases ( IBD ), multiple sclerosis ( MS ), systemic lupus erythematosus , ( SLE ) and systemic scleroderma ( SS ). Plasmalogens may provide a new avenue for treatment as they are essential for many biological systems that serve as molecular targets for oxidative stress and play crucial roles in signalling ,
16 , 17 inflammation , and immune responses .
Increased oxidative stress and the subsequent lipid peroxidation has been proposed as the underlying mechanism leading to reduced plasmalogen levels observed in patients with SLE , 17 MS , 18 SS , 16 and Crohn ’ s disease . 19 Future clinical trials are required to fully understand the drivers and consequences of plasmalogen metabolism in autoimmune diseases ; however , they may provide novel biomarkers for diagnosis and prognosis .
Respiratory diseases Recent findings indicate plasmalogen deficiency may contribute to age-related asthma phenotypes 20 and chronic obstructive pulmonary disease . 21 These results imply that plasmalogens may play a role in normal lung physiology because of their antioxidant potential . 2 Given that plasmalogens are critical for cell membrane integrity , are involved in macrophage phagocytosis and possess anti-inflammatory activity , it has been suggested that plasmalogens may serve as antiviral molecules by inhibiting viral entry and replication in host cells . 22 Moreover , plasmalogen deficiency has been implicated in cardiometabolic and neurodegenerative diseases , thus rendering human hosts more susceptible to certain viral infections . 22
While there is a lack of understanding of the molecular mechanisms involved , a common scenario has emerged involving mitochondrial dysfunction , oxidative stress , inflammation and depleted plasmalogens . Further human trials are required to verify the therapeutic potential of supplementation ; however , changes in plasmalogen levels in several conditions where inflammation plays a key role suggests restoring these lipids may ameliorate certain pathological hallmarks of chronic diseases .
Full reference list available on request .
Disclaimer : The views and opinions expressed in these advertorials are those of the authors and do not necessarily reflect the opinions of ATMS or its Directors .
244 | vol29 | no4 | JATMS