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Modulation of Signal Transduction in Macrophages by Dietary Fatty Acids^1,2,

Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis, CA 95616-8643

Tumor growth can be altered by the amount and type of fat in the diet. Although there are several possible mechanisms for this, recent work suggests that alterations in the immune system by dietary fat may affect tumorigenesis. The focus of recent studies has been on dietary fat modulation of macrophage function because that cell plays a pivotal role in many immune responses, including anti-tumor activity. One possible mechanism of dietary fat effects on macrophages is altered signal transduction, which, in turn, could alter gene regulation and macrophage function. Initial studies tested the effects of dietary fat on kinase activity after stimulation with interferon-gamma. Macrophages from mice fed menhaden fish oil (MFO) had slightly decreased protein kinase C activity compared with macrophages from mice fed safflower oil (SAF). No differences among the diets were observed when the activity of protein kinase A and G were tested. When calcium mobilization was tested, we found that macrophages from mice fed MFO had an increased response compared with macrophages from mice fed SAF. Dietary fat also modified the response of macrophages to platelet-activating factor with respect to the induction of Ia expression. In studies to identify genes involved in dietary fat effects on macrophage function, we screened a cDNA library of macrophages treated with prostaglandin E₂ (PGE₂), a lipid-based mediator that can modulate macrophage function and be altered by dietary fat. The cloned gene, BTG1, was enhanced in macrophages treated with PGE₂, but the relationship with dietary fat remains to be determined. Evidence leads to the conclusion that the effect of dietary fat on macrophages may be a combination of several mechanisms and the modulation of a more complicated set of events.

KEY WORDS: • fat • tumorigenesis • macrophage • immune function • mouse

¹ Presented as part of the symposium "Nutritional Modulation of Lipid-Mediated Signal Transduction Systems" given at Experimental Biology 94 meeting, Anaheim, CA, April 26, 1994. This symposium was sponsored by the American Institute of Nutrition and supported by a grant from the Mead Johnson Corporation. Guest editor for this symposium was Alfred H. Merrill, Jr., Emory University School of Medicine, Atlanta, GA.

² Supported by NIH grant 47050.

³ To whom correspondence should be addressed: Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis, CA 95616-8643.