Diet-Derived Nutrients Modulate the Effects of Amylin on c-Fos Expression in the Area Postrema and on Food Intake

Abstract

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 specifically by the macronutrient composition of the diet. Whereas a low dose of amylin (5 µg/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.

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

“…The reason why blockade of ERK phosphorylation attenuated amylin's ability to reduce eating under some but not all conditions is unclear at present, but may be related to differences in the energy status that affect amylin action (34). Similar to our recent studies using c-Fos immunocytochemistry (34), preliminary data from our group suggest that the amylininduced pERK-expression is lower in rats kept ad libitum prior to amylin-injection and perfusion compared with rats fasted for 24 h (unpublished observation). Consistent with this view, recent studies demonstrate that MAPK/ERK pathway activation is indeed modulated by the nutritional status (20,21).…”

Brainstem mechanisms of amylin-induced anorexia

“…A low dose of peripheral amylin (5 g/kg) induced a strong c-Fos expression in the AP and NTS of 24h-fasted rats, but not in rats fed ad libitum [50]. Similar to fasted rats, the same amylin dose also induced a strong c-Fos response in rats that received a nutrient-deficient non-caloric mash (NCM) for 24 hours before injection.…”

Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure

“…34 Further, GLP-1's eating-inhibitory action seems to differ between fasted versus fed animals because GLP-1 decreased eating when administered to rats after refeeding with a 3 g meal, but not when administered in the fasted state; 63 amylin, in contrast, has been shown to reduce eating when administered to fasted or ad libitum fed animals (for example, Lutz et al, 43 Braegger et al 62 and Michel et al 64 ). The increased effectiveness of GLP-1 to reduce eating in refed animals may be related to an increase in the GLP-1 receptor translocation to the cellular membrane of vagal afferent neurons; the cell bodies of these neurons are located in the nodose ganglion.…”