Ciliary neurotrophic factor (CNTF) induces weight loss by exerting anorexic effects via activation of neurons in the arcuate nuclei of the hypothalamus. Part of the central action of CNTF is due to reduced AMP-activated protein kinase (AMPK) activation. AMPK is a fuel-sensing mediator of metabolic signals, which is activated by an increased AMP/ATP ratio. The present study was carried out to assess the response of CNTF and AMPK to different nutritional signals. CNTF and AMPK expression was determined by Western blot in hypothalamus of female mice after high-fat diet (FAT), high-carbohydrate diet (CARB), caloric restriction (CR), or fasting. After six weeks of controlled diet, body mass of FAT and CARB group was increased by 29.7 and 12.9 %, respectively. CR induced a 5.5 % decrease in body mass, and 18 hours of fasting reduced body mass by 12.5 %. The expression of CNTF was down-regulated in hypothalamus of CARB and CR groups compared to control. The total AMPK expression increased in CARB, FAT, and CR groups. The expression of active form of AMPK was down-regulated after fasting. There was a negative correlation between CNTF and AMPK. These results indicate that diet composition plays a role in the CNTF and AMPK signaling in CNS. Interestingly, CARB diet down-regulated the hypothalamic CNTF expression suggesting that endogenous CNTF has no protective role against high-carb-diet-induced weight gain. On the other hand, CR induced also a decrease in CNTF concentration but in this case to switch off the anorexigenic effect. The increasing amount of total AMPK in CARB and CR groups reflects the regulative role of CNTF i.e. a decrease in hypothalamic CNTF leads to an increase in AMPK expression.