Impaired effects of interleukin-1 beta on fever and thermogenesis in genetically obese rats

Interleukin-1 beta (IL-1 beta) is an endogenous peptide which induced fever (1.8 degrees C rise in colonic temperature) when injected interacerebroventricularly (i.c.v., 80ng human recombinant IL-1 beta) into conscious lean rats. IL-1 beta also stimulated resting oxygen consumption (VO2) by 38 percent, in vitro thermogenic activity (mitochondrial GDP binding) of brown adipose tissue (BAT) by almost two-fold, and blood flow to brown fat (assessed from the distribution of radiolabelled microspheres) by nine-fold in lean animals. Genetically obese Zucker rats showed only small increases in temperature (0.5 degrees C), VO2 (15 percent) and blood flow to BAT (less than two-fold), and no change in GDP binding, but exhibited normal thermogenic responses to i.c.v. injection of corticotrophin releasing factor (GRF). The results indicate that the obese Zucker is insensitive to the central effects of interleukin; this may explain the reduced febrile responses to endotoxin which have previously been reported.