Studies of the effects of dietary fats upon metabolic responses to tumour necrosis factor a, in the wistar rat

Mulrooney, Hilda Mary Teresa (1993) Studies of the effects of dietary fats upon metabolic responses to tumour necrosis factor a, in the wistar rat. University of Southampton, Doctoral Thesis.

Abstract

Tumour necrosis factor alpha (TNFα) is a cytokine which mediates many of the acute phase responses to inflammation. Several of the metabolic effects of this polypeptide can be modulated by dietary changes, particularly alterations in dietary polyunsaturated fat intake. Modulation may occur through modifications in substrate availability for eicosanoid generation, or altered membrane fatty acid composition resulting in modulation of fluidity or receptor activity. A reduced cytokine production may also occur.

Studies documented in this thesis reveal the extent to which both qualitative and quantitative alterations in dietary fat intake can modify metabolic responses to exogenously administered TNFα. Dietary fat can modulate organ weight, fractional rate of protein synthesis, protein concentration and total protein content in the liver and lung, and to a lesser degree, kidney and muscle. Modulation of activity or synthesis of hepatic acute phase proteins is indirectly examined.

Both polynunsaturated and saturated fats are shown to alter acute phase responses. In this thesis, it is shown that the effects of saturated fats do not appear to be due simply to low levels of linoleic acid, but to other compositional differences. The effects of supplementation with the monounsaturate oleic acid are also examined, in order to ascertain the degree to which this fatty acid accounts for the differences observed.

Age appears to affect inflammatory responses to TNFα. Older animals are better able to mount an inflammatory response. Modulatory effects of dietary fats are present in both younger and older animals, but modulation of most responses was greater in the older animals. The hepatic synthesis of acute phase proteins is shown to be particularly affected by age.

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