Comparison of effects of platelet-activating factor and tumour necrosis factor-α on lipid metabolism in adrenalectomized rats in vivo

Abstract

The acute metabolic effects of platelet-activating factor (PAF) and tumour necrosis factor-alpha (TNF-alpha) were compared in sham-operated and adrenalectomized rats. PAF caused hyperglycaemia in sham-operated rats, whereas with TNF-alpha there was a slight decrease in blood glucose. Both PAF and TNF-alpha resulted in marked hypoglycaemia in the adrenalectomized rats. Plasma insulin was depressed (about 50%) by PAF and TNF-alpha in sham-operated rats, whereas in the adrenalectomized rats the already low plasma insulin concentration was not significantly altered. Liver glycogen content was the same in control and treated sham-operated rats, but was considerably decreased (about 50%) in the adrenalectomized rats. In sham-operated rats, PAF and TNF-alpha increased plasma non-esterified fatty acids and triacylglycerols, suggesting increased lipolysis, whereas in adrenalectomized rats there was no significant increase in non-esterified fatty acids with PAF, although it still occurred with TNF-alpha. This suggests that the lipolytic effect of TNF-alpha may be direct, whereas that of PAF is indirect, possibly via increased catecholamines in the sham-operated rats. The stimulation (about 3-fold) of hepatic fatty acid synthesis in vivo by PAF and TNF-alpha in sham-operated rats was still evident in the adrenalectomized rats, although the absolute increase was smaller. PAF, but not TNF-alpha increased (100%) sterol synthesis in adrenalectomized rats. It is concluded that PAF and TNF-alpha can increase hepatic lipogenesis in vivo in the absence of adrenal hormones and in the presence of a low plasma insulin.