Submitted on May 10, 2007
Accepted on July 17, 2007
Interaction of apolipoprotein AIV with cholecystokinin on the regulation of food intake
Chun-Min Lo1, Dianming Zhang1, Kevin Pearson2, Liyun Ma3, William Sun1, Randall R. Sakai3, William Sean Davidson1, Min Liu1, Helen E. Raybould4, Stephen C. Woods3, and Patrick Tso1*
1 Pathology and lab medicine, University of Cincinnati, Cincinnati, Ohio, United States
2 Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States
3 Psychiatry, University of Cincinnati, Cincinnati, Ohio, United States
4 Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, California, United States
* To whom correspondence should be addressed. E-mail: tsopp{at}email.uc.edu.
Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of sub-threshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 µg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 µg/kg. Doses of apo AIV (50 µg/kg) or CCK (0.06 µg/kg) alone had no effects on food intake. However, when these sub-threshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls (P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 plus apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the co-administration of sub-threshold doses of the two peptides is highly satiating and works via CCK1 receptor.
