CENTRAL INSULIN AND MACRONUTRIENT INTAKE IN THE RAT

When rats are maintained on a standard laboratory diet, the infusion o f low doses of insulin into the cerebroventricular system causes a red uction of food intake and body weight. It was recently reported that, if rats are maintained on a high-fat diet (56% calories as fat), they are insensitive to this action of insulin. To investigate further the effect of dietary composition on responsiveness to central insulin, we carried out two experiments. In experiment 1, rats were maintained on one of four equicaloric diets (providing 7, 22, 39, or 54% of calorie s as fat) before and during a 6-day third-ventricular infusion (i3vt) of insulin (10 mU/day) or saline. Rats consuming 7 or 22% of calories as fat had a significant reduction of both food intake (-17.2 +/- 2.9 and -14.6 +/- 3.3 g, respectively) and body weight (-50 +/- 5 and -41 +/- 5 g, respectively) from baseline over the insulin-infusion period. Rats consuming 39 or 54% calories as fat did not reliably alter food intake (-4.0 +/- 3.9 and -1.9 +/- 3.7 g, respectively) or body weight (-10 +/- 6 and -6 +/- 4 g, respectively) in response to i3vt of insuli n. In experiment 2, rats were offered a choice of three macronutrients (carbohydrates, fats, and proteins) in separate jars in their home ca ges. After they had adapted to the diets, they were infused i3vt with insulin or saline. Insulin caused a significant reduction of body weig ht relative to saline-infused controls (body wt: -23.1 +/- 4 g) and a reduction in food intake that was selective for dietary fat. These dat a suggest that the effects of central insulin administration are highl y dependent on the macronutrient content of the diet as well as the ab ility of rats to select their own diets.