Hepatocyte polyunsaturated fatty acid enrichment increases acute phase protein synthesis.

Abstract

The production of acute phase proteins by the liver is critical for homeostasis and recovery after injury. Polyunsaturated fatty acids, specifically of the n-3 family, have demonstrated anti-inflammatory properties that promote recovery; however, the effects of these fatty acids on acute phase protein synthesis have not been fully evaluated. The synthesis of the acute phase proteins alpha-2 macroglobulin and lipopolysaccharide binding protein was studied in hepatocyte-Kupffer's cell cocultures from Wistar rats. Cultures were endotoxin stimulated after enrichment with albumin complexed arachidonic acid (20:4n-6) or docosahexaenoic acid (22:6n-3). Protein synthesis was analyzed by [35S]-methionine labeling or Western blotting. Culture interleukin-6 levels were determined. Both polyunsaturated fatty acids increase hepatocyte synthesis of acute phase proteins alpha 2-macroglobulin and lipopolysaccharide binding protein compared with controls; however, the response in the docosahexaenoic acid (22:6n-3) treated cultures was significant (P < .05 vs control). Interleukin-6 was also increased in the polyunsaturated fatty acid cultures compared with controls (P < .05) vs control). Cellular phospholipids were significantly enriched with the individual supplemented fatty acids (P < .05 vs bovine serum albumin). Polyunsaturated fatty acids have the capability to increase in vitro acute phase protein synthesis. This may contribute to the observed anti-inflammatory effect of n-3 polyunsaturated fatty acid enrichment.