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Am J Physiol Regul Integr Comp Physiol 297: R100-R110, 2009. First published April 29, 2009; doi:10.1152/ajpregu.91014.2008
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ARTICLES

Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the arcuate nucleus of mice during refeeding

Csilla Becskei, Thomas A. Lutz, and Thomas Riediger

Institute of Veterinary Physiology and Zurich Centre of Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Submitted 15 December 2008 ; accepted in final form 24 April 2009

Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow. Here, we investigated the contribution of diet-derived macronutrients and anorectic hormones to the reversal of the fasting-induced ARC activation during 2 h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric mash induced only a small reduction in c-Fos expression. Refeeding with diets, containing carbohydrates, protein, or fat alone reversed it similar to chow; however, this effect depended on the amount of intake. The fasting-induced ARC activation was unchanged by subcutaneously injected amylin, CCK (both 20 µg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin-containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin-induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK may inhibit orexigenic ARC neurons when acting together with other feeding-related signals. We conclude that all three macronutrients and also non-nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.

c-Fos; insulin; leptin; amylin; cholecystokinin



Address for reprint requests and other correspondence: T. Riediger, Institute of Veterinary Physiology, Univ. of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland (e-mail: triedig{at}vetphys.uzh.ch)







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