Modulation of metabolic effects of TNFα by dietary fats

Abstract

Cytokines mediate many of the metabolic changes that occur during infection and are implicated in chronic inflammatory diseases such as rheumatoid arthritis. Fish oil has been shown to moderate their inflammatory effects by alteration of eicosanoid metabolism. This study compares the response of mice to TNFa after seven weeks of feeding diets rich in n-6 polyunsaturated fatty acids (PUFAs) fed as corn oil, or poor in n-6 PUFAs fed as fish or coconut oil or suet. The latter three fats, although similar in this respect, differ in that suet is rich in the mono-unsaturated fatty acid, oleic acid (C18:l) while coconut oil is rich in saturated fatty acids of medium carbon chain lengths, lauric and myristic acids (C12:0 and C14:0) and fish oil has a high content of n-3 PUFAs. Responses in mice fed corn oil were regarded as normal. Protein fractional synthetic rates and content were measured in liver, lung and muscle, caeruloplasmin concentration in serum and zinc concentration in liver. While TNF failed to change protein content or synthetic rate in liver and muscle, substantial changes occurred in the lung in animals fed corn oil. The findings contrast with those of studies using rats where substantial increases occur in liver and lung. Feeding coconut oil reduced the response of protein synthesis in lung, suet abolished the response and fish oil changed the effect of TNF to an inhibition of synthesis. Liver zinc concentration was only increased in mice fed corn oil but caeruloplasmin was increased by TNF in all dietary groups. The studies indicate substantial differences in intra-species and intra-tissue sensitivity to the actions of recombinant human TNFα. While fats low in linoleic acid modulate the effect of TNFα on lung, the extent and nature of the modulation is influenced by other characteristics of the fat.