Elevated neuronal c-Fos-like immunoreactivity and messenger ribonucleic acid (mRNA) in genetically obese (ob/ob) mice.
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 fold 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 arcuate 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Mistry
A M
AM
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224.
Helferich
W
W
Romsos
D R
DR
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology*; D016762:Genes, fos; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis*
D009478:Neuropeptide Y; D012333:RNA, Messenger