Lipid Metabolism and Brain Health

Dear Colleagues,

The brain is the second most lipid-rich organ in the body and lipid metabolism is closely linked to brain energy homeostasis, oxidative stress, neuroinflammation, and imbalances in neuroglial cell lipid metabolism affecting normal neuronal activity (Yang et al., 2022). The brain contains large amounts of sphingolipids, glycerophospholipids, and cholesterol, which are involved in synaptogenesis, neurogenesis, and impulse transmission, and are inextricably linked to the development and maintenance of the brain and the proper conduct of many other cellular processes (Cermenati et al., 2005; Korade and Kenworthy, 2008). However, lipid accumulation production of lipotoxic metabolites induced by impaired lipid metabolism in the brain may further trigger central nervous system diseases and injuries (Han and Kaufman, 2016). Cholesterol, among all the lipids present in astrocytes, may play the most critical role in the structure of these cells. Among the subtypes of glia, oligodendrocytes produce cholesterol for myelin formation, which is involved in brain maturation and neurotransmission, while astrocytes are thought to be the main site of exogenous neuronal cholesterol synthesis (Linetti et al., 2010; Koudinov and Koudinova, 2002). Sphingolipids (SP) are the major lipids that compose the brain and the functional units of neuronal cell membranes and are highly enriched in the nervous system. Although the types of SP that may contribute to neurological dysfunction are unknown, genetic defects in various sphingolipid metabolizing enzymes reveal the importance of sphingolipid metabolism in brain development and health (Astudillo et al., 2015). Lipid droplets (LDs) are first recognized as independent organelles associated with lipid storage and transport, serving as relatively simple storage particles for lipids in the brain (Cermenati et al., 2005). While the brain is under pathological conditions, the content of LDs in glial cells is increased, though to a lesser extent in neurons. It has been controversial whether this lipid accumulation under stress has a protective or detrimental effect on the brain. LDs are highly regulated organelles that contribute to many cellular processes and emerge as metabolic hubs with diverse roles in energy and signalling precursors storage, cell stress management, and protein handling (Linetti et al., 2010; Boyles et al., 1989).

PUFAs are incorporated into membrane phospholipids and therefore play a significant role in the structural integrity and function of cell membranes. The lipid metabolism is changed during ageing (Montanini et al., 1983), as shown by a decline in omega-3 fatty acids and an increase in lipid peroxidation (Chen, 2017). Omega-3 fatty acids have antioxidant properties, and a lack of these fatty acids in one’s diet may accelerate neuronal degeneration (Yehuda et al., 2002). Susceptibility of lipids to peroxidation increases with age (Bourre and Vitamin, 1991), which supports the use of the level of oxidative stress as a critical determinant of neuronal health and longevity (Hulbert et al., 2006). Previous studies have suggested that DHA and EPA may protect against peroxidation and the effects of age-related brain pathology (Hasadsri et al., 2013). Lipids are involved in cellular signalling, energy balance, blood–brain barrier (BBB), and inflammation (Song C, et al., 2008), and such age-dependent lipidome changes that disrupt these functions may contribute to neurodegenerative diseases (Arnoldussen et al., 2016). Brain lipids confer a myriad of functions to the maintenance of a healthy brain and impaired brain health is the number one global health crisis. This Special Issue is dedicated to collecting the latest research and knowledge present in the scientific community in relation to how the lipid metabolism influences brain health outcomes. We encourage researchers to submit any studies related to the brain lipid metabolism and how this converges to either positively or negatively influence brain health outcomes, as well as any strategies that may be useful as part of a management system aimed at addressing brain health as a global health crisis.  

References

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Dr. Raymond H. Thomas
Dr. Elham Momeny
Guest Editors

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