Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake.
Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The third ventricular (i3vt) administration of a subthreshold dose of apo A-IV (0.5 microg) potentiated i3vt MC-induced (metallothionein-II, 0.03 nmol) suppression of 30-min feeding in Long-Evans rats. A subthreshold dose of the MC antagonist (SHU9119, 0.1 nmol, i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 microg). The i3vt apo A-IV significantly elevated the expression of c-Fos in neurons of the paraventricular nucleus of the hypothalamus, but not in the arcuate nucleus or median eminence. In addition, c-Fos expression was not colocalized with proopiomelanocortin-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.
Gotoh
Koro
K
Department of Psychiatry, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH 45237, USA.
Liu
Min
M
Benoit
Stephen C
SC
Clegg
Deborah J
DJ
Davidson
W Sean
WS
D'Alessio
David
D
Seeley
Randy J
RJ
Tso
Patrick
P
Woods
Stephen C
SC
D000818:Animals; D001054:Apolipoproteins A / Q000494:pharmacology* / Q000502:physiology; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology*; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008668:Metallothionein / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans
D001054:Apolipoproteins A; C022205:apolipoprotein A-IV; C103272:SHU 9119; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones; D008668:Metallothionein