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Am J Physiol Regul Integr Comp Physiol 290: R202-R207, 2006. First published September 15, 2005; doi:10.1152/ajpregu.00502.2005
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake

Koro Gotoh,1 Min Liu,2 Stephen C. Benoit,1 Deborah J. Clegg,1 W. Sean Davidson,2 David D'Alessio,3 Randy J. Seeley,1 Patrick Tso,2 and Stephen C. Woods1

Departments of 1Psychiatry, 2Pathology, and 3Medicine, University of Cincinnati, Cincinnati, Ohio

Submitted 11 July 2005 ; accepted in final form 25 August 2005

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 µg) 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 µg). 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.

melanocortin system; hypothalamus; proopiomelanocortin; c-Fos


Address for reprint requests and other correspondence: S. C. Woods, Dept. of Psychiatry, Univ. of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH 45237 (e-mail: steve.woods{at}psychiatry.uc.edu)




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[Abstract] [Full Text] [PDF]


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