Inhibition of the thermogenic and pyrogenic responses to interleukin-1β in the rat by dietary N-3 fatty acid supplementation

Abstract

The thermogenic (increase in oxygen consumption, VO 2) and pyrogenic (Tc) responses to the cytokine interleukin-1β (IL-1β) were studied in rats fed a n-3 fatty acid supplemented diet (8.75% n-3 fatty acids/kg diet). 4–6 weeks after commencing the diets, the n-3 supplemented rats exhibited reduced pyrogenic (0.5 ± 0.1°C versus 1.1 ± 0.2°C in control animals) and thermogenic (9 ± 3% versus 22 ± 6% in control animals) responses to intraperitoneal (i.p.) injection of IL-1β (1 μg/rat). However, responses to centrally administered IL-1β (5ng intracerebroventricular (i.c.v.)) were similar in both groups at this time. After 8–9 weeks of supplementation, n-3 supplemented animals exhibited attenuated responses to both in IL-1β (VO 2 responses reduced by 68% and Tc by 0.8°C) and also i.c.v. IL-1β (VO 2 responses reduced by 56% and Tc by 0.7°C). N-3 supplementation did not, however, influence the thermogenic capacity of these animals since responses to noradrenaline were similar in control and n-3 fed animals (50% increase in VO 2). These findings demonstrate that n-3 supplementation modifies the pyrogenic and thermogenic responses to IL-1β, probably via changes in eicosanoid metabolism. Modification of central responses to IL-1 are delayed compared to the effects of peripheral administration indicating separate mechanisms of IL-1 on fever and thermogenesis in the brain and the periphery.