Anorexigenic C75 alters c-Fos in mouse hypothalamic and hindbrain subnuclei.
The fatty acid synthase inhibitor C75 reduces feeding rapidly and for several days. We investigated brain sites potentially involved in actions of i.p. C75 in mice by examining c-Fos. At 3 h C75 increased numbers of c-Fos-immunoreactive cells in hindbrain feeding-related nuclei, and in the paraventricular nucleus (PVN), lateral aspects of the arcuate nucleus (ARC), and in the central amygdala. At 24 h C75 prevented fasting-induced c-Fos expression in the medial ARC and three of its targets: lateral magnocellular PVN, lateral hypothalamus, and dorsomedial hypothalamus. C75, but not fasting, increased c-Fos in parvocellular PVN. This pattern of results suggests a shift from hindbrain-initiated short-term actions to activation of hypothalamic mechanisms that could mediate the long-term anorectic responses to C75.
Miller
Ian
I
Departments of Neuroscience and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ronnett
Gabriele V
GV
Moran
Timothy H
TH
Aja
Susan
S
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism; D007031:Hypothalamus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012249:Rhombencephalon / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D015107:4-Butyrolactone