Fasting-induced increases in food intake and neuropeptide Y gene expression are attenuated in aging male Brown Norway rats

Aging in man is associated with alterations in food intake (FI) and body weight (BW). To establish a model of age-related alterations in Fl and BW regulation, Fl and BW were determined in young (3-month-old), middle-aged (12-month-old), and old (24-month-old) male Brown Norway rats during ad libitum Feeding and after 72 h of fasting. FI was reduced with aging both during ad libitum feeding and after fasting. With fasting, young rats lost more BW than older rats, but regained BW more rapidly during refeeding. To determine whether age-related impairments in FI and BW regulation are mediated by neuropeptide Y (NPY), a potent stimulator of FI, we compared arcuate nucleus prepro-NPY (ppNPY) messenger RNA (mRNA) by in situ hybridization in fasted and ad libitum-fed (fed) young, middle-aged, and old rats. ppNPY mRNA declined with aging in both fed and fasted rats. Although ppNPY mRNA increased with fasting in all age groups, this response was attenuated with aging. In conclusion, impaired FI and BW recovery after fasting is associated with reduced NPY responsiveness to fasting in aging rats. Impaired activation of the hypothalamic NPY pathway may, therefore, contribute to age-related alterations in FI and BW regulation.