Effect of nutrition on tumor necrosis factor receptors in weight-gaining and -losing rats

Previous studies showed that weight-gaining rats had greater retention and reduced turnover of 125I-labeled tumor necrosis factor (TNF)-alpha in the circulation compared with weight-losing animals. We therefore tested the hypothesis that protein-energy restriction with weight loss reduces the levels of soluble TNF-alpha receptor (sTNFR) and membrane TNFR (mTNFR) and the cellular expression of TNF-alpha mRNA. Twenty-six male rats weighing 200-220 g were fed a liquid formula diet for 10 days and divided equally into weight-gaining rats meeting all nutritional requirements (WG rats) and weight-losing rats with protein-energy restriction (WL rats). 125I-TNF-alpha binding was demonstrated in plasma and plasma membrane to proteins of molecular masses of 92 and 243 kDa, a finding identical to that seen with purified human p55. Excess unlabeled TNF-alpha displaced the binding showing its specificity. The degree of binding to plasma protein and liver plasma membrane was markedly reduced in WL rats. Northern analysis showed that the expression of p55 mRNA was increased in the lungs and reduced in kidneys of WL compared with WG rats. The expression of p75 mRNA was not influenced by the nutritional status. We conclude that levels of sTNFR and mTNFR were reduced in WL rats. Reduced sTNFR and liver mTNFR are not due to a reduction in the expression of either p55 or p75 mRNA in WL rats. Reduced mTNFR, together with reduced shedding of soluble receptors, may have a protective role in WL rats.