1: Surgery. 1998 Aug;124(2):471-6. Links
Hepatocyte polyunsaturated fatty acid enrichment increases acute phase protein synthesis.Nolan B, Sentementes J, Bankey P.
Department of Surgery, University of Massachusetts, Worcester 01655-0333, USA.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
1: Cancer Res. 1991 Nov 15;51(22):6089-93. Links
Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover.Beck SA, Smith KL, Tisdale MJ.
Cancer Research Campaign Experimental Chemotherapy Group, Aston University, Birmingham, United Kingdom.
The effect of the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) on host body weight loss and tumor growth has been investigated in mice bearing a cachexia-inducing colon adenocarcinoma, the MAC16. EPA effectively inhibited both host weight loss and tumor growth rate in a dose-related manner with optimal effects being observed at a dose level of 1.25 to 2.5 g/kg. At these concentrations host body weight was effectively maintained, and there was a delay in the progression of growth of the tumor, such that overall survival was approximately doubled in EPA-treated animals, using the criteria dictated by the United Kingdom Coordinating Committee for the welfare of animals with neoplasms. Even when tumor growth resumed, weight loss did not occur. Animals bearing the MAC16 tumor showed a decreased protein synthesis and an increased degradation in skeletal muscle. Treatment with EPA significantly reduced protein degradation without an effect on protein synthesis. The effect of GLA on both host body weight loss and tumor growth was much less pronounced than that of EPA, with an effect only being seen at a dose of 5 g/kg, at which some toxicity was observed. In vitro studies showed that while EPA was effective in inhibiting tumor-induced lipolysis, GLA was ineffective in this respect. However, prostaglandin E1, which is formed from GLA in vivo, showed partial reversal of tumor-induced lipolysis and probably accounted for the anticachectic effect of GLA. These results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.
NOTE- cox-2 inhibition is mechanistically different than pharmaceutical cox-2 inhibitors (though in studies their effects are complementary)