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Am J Physiol Regul Integr Comp Physiol (September 15, 2005). doi:10.1152/ajpregu.00502.2005
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Submitted on July 11, 2005
Accepted on August 25, 2005

Apolipoprotein A-IV Interacts Synergistically with Melanocortins to Reduce Food Intake

Koro Gotoh1, Min Liu2, Stephen C Benoit1, Deborah J Clegg1, W. Sean Davidson2, David D'Alessio3, Randy J Seeley1, Patrick Tso1, and Stephen C Woods1*

1 Psychiatry, University of Cincinnati, Cincinnati, Ohio, USA
2 Pathology, University of Cincinnati, Cincinnati, Ohio, USA
3 Medicine, University of Cincinnati, Cincinnati, Ohio, USA

* To whom correspondence should be addressed. E-mail: steve.woods{at}psychiatry.uc.edu.

Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine if apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The 3rd-ventricular [i3vt] administration of a sub-threshold dose of apo A-IV (0.5 µg) potentiated i3vt melanocortin (MT-II, 0.03 nmol)-induced suppression of 30-min feeding in Long-Evans rats. A sub-threshold dose of the melanocortin antagonist (SHU9119, 0.1nmol,i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 µg). I3vt apo A-IV elevated significantly the expression of c-Fos in neurons of the paraventricular nucleus (PVN) of the hypothalamus, but not in the arcuate nucleus (ARC) or median eminence (ME). In addition, c-fos expression was not colocalized with POMC-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.




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[Abstract] [Full Text] [PDF]


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