Effect of enterostatin and kappa-opioids on macronutrient selection and consumption

Enterostatin, the activation peptide of pancreatic procolipase, suppresses consumption of high-fat diets and selectively suppresses fat consumption over carbohydrate consumption. Kappa-opioid subtype agonists stimulate feeding whereas antagonists suppress feeding. We investigated the effects of enterostatin, the kappa-opioid agonist U50488, and the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) on macronutrient selection and food consumption in rats adapted to choose between a high-fat (HF) diet or a low-fat-high-carbohydrate (LF) diet. In fasted rats, lateral cerebro-ventricular injection (LV) of enterostatin selectively suppressed consumption of the HF diet, with no effect on LF diet consumption. Nor-BNI also selectively suppressed consumption of the HF diet without affecting LF diet consumption. Additionally, U50488 prevented the suppression of consumption of the HF diet in response to enterostatin. In food-sated rates, U50488 preferentially increased consumption of the HF diet and had no effect on consumption of the LF diet. Combined infusions of subthreshold doses of enterostatin and nor-BNI also inhibited consumption of the HF but not the LF diet, whereas combined infusions of maximal doses of enterostatin and nor-BNI had no additive effects. Collectively, these data suggest that a kappa-opioid pathway modulates selection and consumption of diets high in fat and that enterostatin modulates consumption of dietary fat by interacting with this pathway.