Diet-derived nutrients modulate the effects of amylin on c-Fos expression in the area postrema and on food intake

The pancreatic hormone amylin decreases food intake via activation of area postrema ( AP) neurons. We investigated whether amylin's potency to reduce food intake and to induce c- Fos expression in the AP/ nucleus of the solitary tract region is affected by the feeding conditions and specifical ly by the macronutrient composition of the diet. Whereas a low dose of amylin ( 5 mu g/ kg s. c.) induced very little c- Fos expression in ad libitum chow fed rats, it caused a strong c- Fos expression in 24- hour food- deprived rats and in rats that received a nutrient- deficient non- caloric mash ( NCM; vanilla- flavoured cellulose) 24 h before injection. To reveal the contribution of single nutrients to the low c- Fos expression after chow feeding, amylin- induced c- Fos was analyzed after feeding NCM that was selectively supplemented with glucose, fat ( lard), or protein ( casein), matching the intake of these nutrients of chow- fed rats. While the rats fed NCM supplemented with glucose or fat displayed an equally strong amylin- induced activation as fasted rats or rats fed plain NCM, a significantly lower c- Fos expression was observed in rats fed a protein- supplemented NCM or a NCM containing all three nutrients. In line with this lower activation, the same dose of amylin failed to reduce food intake in NCM/ protein-fed rats, while amylin caused a reduction in feeding when animals received NCM, NCM/ glucose, or NCM/ fat. Interestingly, amylin effectively reduced food intake in ad libitum chow fed rats despite the low level of amylin- induced c- Fos expression in the AP under these conditions. We conclude that the anorectic potential of amylin may be attenuated by diet- derived proteins, whereas this effect appears to be overridden when the amount of carbohydrates/ fat is high relative to the protein content, such as, e. g., in standard chow. Copyright (C) 2007 S. Karger AG, Basel.