The nutritional and clinical significance of lipid rafts

Purpose of review Lipid rafts are potentially modifiable by diet, particularly (but not exclusively) by dietary fatty acids. This review examines the potential for dietary modification of raft structure and function in the immune system, brain and retinal tissue, the gut, and in cancer cells. Recent findings In-vitro and ex-vivo studies suggest that dietary n-3 polyunsaturated fatty acids (PUFAs) may exert immunosuppressive and anticancer effects through changes in lipid raft organization. In addition, gangliosides and cholesterol may modulate lipid raft organization in a number of tissues, and recent work has highlighted sphingolipids in membrane microdomains as potential targets for inhibition of tumor growth. The roles of fatty acids and gangliosides, especially in relation to lipid rafts, in cognitive development, age-related cognitive decline, psychiatric disorders, and Alzheimer’s disease are poorly understood and require further investigation. The roles of lipid rafts in cancer, in microbial pathogenesis, and in insulin resistance are starting to emerge, and indicate compelling evidence for the growing importance of membrane microdomains in health and disease. Summary In-vitro and animal studies show that n-3 PUFAs, cholesterol, and gangliosides modulate the structure and composition of lipid rafts, potentially influencing a wide range of biological processes, including immune function, neuronal signaling, cancer cell growth, entry of pathogens through the gut barrier, and insulin resistance in metabolic disorders. The physiological, clinical, and nutritional relevance of these observations remains to be determined.

The Nutritional Significance of Lipid Rafts

The structure, size, stability, and functionality of lipid rafts are still in debate, but recent techniques allowing direct visualization have characterized them in a wide range of cell types. Lipid rafts are potentially modifiable by diet, particularly (but not exclusively) by dietary fatty acids. However, it is not clear whether dietary polyunsaturated fatty acids (PUFAs) are incorporated into raft lipids or whether their low affinity to cholesterol disallows this and causes phase separation from rafts and displacement of raft proteins. This review examines the potential for dietary modification of raft structure and function in the immune system, brain and retinal tissue, the gut, and in cancer cells. Although there is increasing evidence to suggest that membrane microdomains, and their modulation, have an impact in health and disease, it is too early to judge whether modulation of lipid rafts is responsible for the immunomodulatory effects of n-3 PUFA. In addition to dietary fatty acids, gangliosides and cholesterol may also modulate microdomains in a number of tissues, and recent work has highlighted sphingolipids in membrane microdomains as potential targets for inhibition of tumor growth by n-3 PUFA. The roles of fatty acids and gangliosides in cognitive development, age-related cognitive decline, psychiatric disorders, and Alzheimer's disease are poorly understood and require clarification, particularly with respect to the contribution of lipid rafts. The roles of lipid rafts in cancer, in microbial pathogenesis, and in insulin resistance are only just emerging, but compelling evidence indicates the growing importance of membrane microdomains in health and disease.