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Am J Physiol Regul Integr Comp Physiol (July 30, 2008). doi:10.1152/ajpregu.90381.2008
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Submitted on April 23, 2008
Revised on July 14, 2008
Accepted on July 24, 2008

Intraperitoneal injections of low doses of C75 elicit a behaviorally specific and vagal afferent-independent inhibition of eating in rats

Abdelhak Mansouri1, Susan Aja2, Timothy H. Moran3, Gabriele V. Ronnett4, Francis Paul Kuhajda3, Myrtha Arnold1, Nori Geary1, Wolfgang Langhans5*, and Monika Leonhardt1

1 ETH Zurich
2 Johns Hopkins School of Medicine
3 Johns Hopkins University School of Medicine
4 Johns Hopkins university School of Medicine
5 Swiss Federal Institute of Technology

* To whom correspondence should be addressed. E-mail: wolfgang-langhans{at}ethz.ch.

Central and intraperitoneal (IP) C75, an inhibitor of fatty acid synthase (FAS) and stimulator of carnitine palmitoyl-transferase-1 (CPT-1), inhibits eating in mice and rats. Mechanisms involved in feeding inhibition after central C75 have been identified, but little is yet known about how systemic C75 might inhibit eating. One issue is whether IP C75 reduces food intake in rats by influencing normal physiological controls of food intake or acts non-selectively, for example by eliciting illness or aversion. Another issue relates to whether IP C75 acts centrally or, similar to some other peripheral metabolic controls of eating, activates abdominal vagal afferents to inhibit eating. To further address these questions, we investigated the effects of IP C75 on spontaneous meal patterns and the formation of conditioned taste aversions (CTA). We also tested whether IP C75's eating-inhibitory effect is vagally mediated by testing rats after either total subdiaphragmatic vagotomy (TVX) or selective subdiaphragmatic vagal deafferentations (SDA). IP injection of 3.2 and 7.5 mg/kg C75 significantly reduced food intake 3, 12 and 24 h after injection by reducing the number of meals without affecting meal size, whereas 15 mg/kg C75 reduced both meal number and meal size. The two smaller doses of C75 failed to induce a CTA, but 15 mg/kg C75 did. C75's eating-inhibitory effect was not diminished in either TVX or SDA rats. We conclude that IP injections of low doses of C75 inhibit eating in a behaviorally specific manner and that this effect does not require abdominal vagal afferents.







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