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Modulation of Lipid Rafts by -3 Fatty Acids in Inflammation and Cancer: Implications for Use of Lipids During Nutrition Support

Rafat A. Siddiqui, PhD^*, Kevin A. Harvey, BS^*, Gary P. Zaloga, MD and William Stillwell, PhD

^* Methodist Research Institute, Clarian Health Partners, Indianapolis, Indiana; Baxter Health Care, Deerfield, Illinois; and Departments of Medicine and Biology, Indiana University–Purdue University, Indianapolis, Indiana

Correspondence: Rafat A. Siddiqui, PhD, Methodist Research Institute, Cellular Biochemistry, E504D, 1800 N. Capitol Ave., Indianapolis, IN 46202. Electronic mail may be sent to rsiddiqu{at}clarian.org.

Current understanding of biologic membrane structure and function is largely based on the concept of lipid rafts. Lipid rafts are composed primarily of tightly packed, liquid-ordered sphingolipids/cholesterol/saturated phospholipids that float in a sea of more unsaturated and loosely packed, liquid-disordered lipids. Lipid rafts have important clinical implications because many important membrane-signaling proteins are located within the raft regions of the membrane, and alterations in raft structure can alter activity of these signaling proteins. Because rafts are lipid-based, their composition, structure, and function are susceptible to manipulation by dietary components such as -3 polyunsaturated fatty acids and by cholesterol depletion. We review how alteration of raft lipids affects the raft/nonraft localization and hence the function of several proteins involved in cell signaling. We focus our discussion of raft-signaling proteins on inflammation and cancer.

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