Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents.
Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined in male rats injected ip before onset of dark or light phase, with obestatin (1 or 5 micromol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl, after fasting (16 h, n=8/group) or ad libitum (n=10-14/group) food intake. Fos expression in hypothalamic and brainstem nuclei was examined in freely fed rats 90 min after obestatin (5 micromol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl (n=4/group). Additionally, fasted mice were injected ip with obestatin (1 micromol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No effect on FI was observed after obestatin administration during the light and dark phase under both metabolic conditions while CCK8S reduced FI irrespectively of the conditions. The number of Fos positive neurons was not modified by obestatin while CCK8S increased Fos expression in selective brain nuclei. Obestatin did not influence the refeeding response to a fast in mice, while urocortin was effective. Therefore, peripheral obestatin has no effect on FI under various experimental conditions and did not induce Fos in relevant central neuronal circuitries modulating feeding in rodents.
Kobelt
Peter
P
Department of Medicine, Division Psychosomatic Medicine and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Wisser
Anna-Sophia
AS
Stengel
Andreas
A
Goebel
Miriam
M
Bannert
Norbert
N
Gourcerol
Guillaume
G
Inhoff
Tobias
T
Noetzel
Steffen
S
Wiedenmann
Bertram
B
Klapp
Burghard F
BF
Taché
Yvette
Y
Mönnikes
Hubert
H
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000502:physiology*; D005215:Fasting; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017440:Photoperiod; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013851:Thinness / Q000503:physiopathology; D013997:Time Factors
D054439:Ghrelin; D016760:Proto-Oncogene Proteins c-fos