Elevated neuronal c-Fos-like immunoreactivity and messenger ribonucleic acid (mRNA) in genetically obese ( ob/ob) mice

Abstract

Adult genetically obese ( ob/ob) mice display a number of metabolic alterations, the primary cause of which may be a defect in their central nervous system (CNS). The protein encoded by the protooncogene c- fos, c-Fos, functions as a nuclear transcription factor, and also serves as a marker of neuronal activity. The specific objectives of this study were (1) to use c-Fos immunohistochemistry to identify regions with altered neuronal activity in 6–7 week old male lean and ob/ob mice; (2) to examine c- fos relative mRNA abundance by northern blot analysis in brains of these mice and compare it with that of neuropeptide Y (NPY), a peptide well known to alter feeding and (3) determine changes in c-Fos immunoreactivity and mRNA caused by food deprivation. Fos-like immunoreactivity (FLI) tended to be higher in ad libitum fed ob/ob mice than in lean controls in most brain regions examined. The most prominent and consistent differences were in the paraventricular nuclei (PVN) where the numbers of Fos-positive nuclei were approximately 3 hold higher in ob/ob mice. Food deprivation for 24 h increased FLI in the PVN in lean mice but did not further augment FLI in the PVN of ob/ob mice. Arcuate nuclei of lean and ob/ob mice showed minimal FLI staining under ad libitum fed conditions. Food deprivation however, induced FLI in acurate nuclei of both lean and ob/ob mice. The abundance of c- fos mRNA in whole brain of ob/ob mice averaged several fold higher than in leans under both fed and fasted conditions. There was no difference in whole brain NPY mRNA between lean and ob/ob mice. Prolonged stimulation of c-Fos in specific neurons of ob/ob mice including the paraventricular nucleus probably has modulatory effects on certain genes which in turn account for long term adaptive changes of the ob/ob phenotype.