Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity.

We examined the effect of dietary fat on the response to 3-hydroxybutyrate (3-OHB) and insulin infused chronically into the third ventricle in three strains of rats with differing susceptibility to obesity induced by a high-fat diet: Osborne-Mendel rats are most susceptible; Sprague-Dawley-rats are intermediate; and S 5B/Pl rats are most resistant. Ten days after implantation of cannulas into the third ventricle, rats were fed either a low-fat diet or a high-fat diet for 14 days. On day 7, osmotic minipumps were attached to the ventricular cannulas. 3-OHB infusions (3.6 mumol/24 h) reduced food intake and body weight in Sprague-Dawley and Osborne-Mendel rats eating either diet. The dietary fat-resistant S 5B/Pl rats did not respond to the intracerebroventricular infusion of 3-OHB. The infusion of insulin (10 mU/24 h) lowered food intake and body weight in animals eating the low-fat (high-carbohydrate) diet but not in animals eating the high-fat diet. Diet profoundly affects the response to intracerebroventricular infusions of insulin but is without effect on the response to 3-OHB.