When people think about the brain, they often imagine neurons firing electrical signals or complex networks controlling thoughts and behavior. However, what is frequently overlooked is that a large portion of the brain is composed of lipids. In fact, lipids account for more than 50% of the brain’s dry weight, yet they have not received the same level of attention as other macromolecules. Although lipidomics is one of the fastest-growing omics fields, it is still underrepresented compared to transcriptomics, metabolomics, genomics and proteomics. Bibliometric analyses report fewer than 8,000 publications over the past two decades, suggesting a relatively small research community focused on lipid biology. This raises an important question: why are lipids not studied more extensively in the context of brain health and disease?
Lipids are water-insoluble molecules, including fats, oils, and cholesterol, that are essential for life. While they are commonly associated with energy storage, their functions extend far beyond that. Lipids are key components of cell membranes, support hormone production, and protect tissues. In the brain, their roles are even more critical. Lipids are not merely passive building blocks; they actively influence how the brain functions. For instance, phospholipids and cholesterol provide cell membranes with the appropriate balance of fluidity and stability, enabling efficient signal transmission between neurons.
Sphingolipids and cholesterol are also major components of myelin, the insulating layer that allows rapid conduction of electrical signals along nerve fibers. Additionally, specific fatty acids such as DHA and arachidonic acid are essential for synaptic plasticity, a process underlying learning and memory. Lipids can also serve as alternative energy sources and, in some cases, protect brain cells by reducing inflammation and oxidative stress.
When lipid balance is disrupted, serious consequences can arise. Alterations in lipid composition have been linked to neurodegenerative diseases such as Alzheimer’s, Parkinson’s, brain cancer and so on, demonstrating that lipids are deeply involved in disease processes. Changes in lipid environments can affect protein behavior, promoting misfolding and aggregation into toxic structures that damage neurons. This is particularly relevant in conditions where protein aggregation is a hallmark feature.
Lipids also play a crucial role in maintaining mitochondrial health. Mitochondria rely on specific lipids such as cardiolipin for proper function. Disruption of these lipids can impair energy production, increase oxidative stress, and render neurons more vulnerable to degeneration. Given the brain’s high energy demand, even small disturbances in mitochondrial lipid composition can have significant effects on neuronal survival.
The growing recognition of these roles has led to increased interest in brain lipidomics, a field focused on analyzing the full spectrum of lipids within the brain. Advances in analytical technologies, particularly mass spectrometry, now allow researchers to identify and quantify hundreds to thousands of lipid species in a single experiment. This provides a systems-level understanding of how lipid profiles change with aging, diet, environmental exposure, and disease progression.
Lipidomics also holds promise for improving diagnosis and treatment of neurological disorders. Changes in lipid profiles may serve as early biomarkers, sometimes appearing before clinical symptoms develop. This creates opportunities for earlier detection and intervention. Furthermore, targeting lipid metabolism offers new therapeutic strategies, including dietary modifications, drugs that restore lipid balance, and approaches that protect mitochondrial integrity.
For individuals interested in contributing to this interdisciplinary field, lipidomics offers multiple accessible pathways. A background in biochemistry, neuroscience, or molecular biology provides a strong foundation. Developing skills in analytical techniques such as mass spectrometry, chromatography, and data analysis is highly valuable. Many researchers transition into lipidomics from related fields like metabolomics or cell biology. Collaboration is also essential, as the field bridges biology, analytical chemistry, and bioinformatics. Expanding research in lipidomics is crucial for advancing our understanding of brain health and developing more effective treatments for neurological diseases.
References
Géhin C, Fowler SJ, Trivedi DK. Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022. Anal Sci Adv. 2023 May 10;4(3-4):104-131. doi: 10.1002/ansa.202300009. PMID: 38715925; PMCID: PMC10989624.
Li, P., Sun, Z., Chen, X. et al. Mapping current research status and emerging frontiers of lipidomics: a comprehensive data-mining-based study. Metabolomics 21, 85 (2025). https://doi.org/10.1007/s11306-025-02292-6.
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