Altered Hypothalamic Signaling and Responses to Food Deprivation in Rats Fed a Low‐Carbohydrate Diet

OBJECTIVE: To model how consuming a low-carbohydrate (LC) diet influences food intake and body weight. RESEARCH METHODS AND PROCEDURES: Food intake and body weight were monitored in rats with access to chow (CH), LC-high-fat (HF), or HF diets. After 8 weeks, rats received intracerebroventricular injections of a melanocortin agonist (melanotan-II) and antagonist (SHU9119), and feeding responses were measured. At sacrifice, plasma hormones and hypothalamic expression of mRNA for proopiomelanocortin (POMC), melanocortin-4 receptor, neuropeptide Y (NPY), and agouti related protein (AgRP) were assessed. A second set of rats had access to diet (chow or LC-HF) for 4 weeks followed by 24 h food deprivation on two occasions, after which food intake and hypothalamic POMC, NPY, and AgRP mRNA expression were measured. RESULTS: HF rats consumed more food and gained more weight than rats on CH or LC-HF diets. Despite similar intakes and weight gains, LC-HF rats had increased adiposity relative to CH rats. LC-HF rats were more sensitive to melanotan-II and less sensitive to SHU9119. LC-HF rats had increased plasma leptin and ghrelin levels and decreased insulin levels, and patterns of NPY and POMC mRNA expression were consistent with those of food-deprived rats. LC-HF rats did not show rebound hyperphagia after food deprivation, and levels NPY, POMC, and AgRP mRNA expression were not affected by deprivation. DISCUSSION: Our results demonstrate that an LC diet influences multiple systems involved in the controls of food intake and body weight. These data also suggest that maintenance on an LC-HF diet affects food intake by reducing compensatory responses to food deprivation.