PERIPHERAL 3-HYDROXYBUTYRATE AND FOOD-INTAKE IN A MODEL OF DIETARY-FAT INDUCED OBESITY - EFFECT OF VAGOTOMY

We have examined the effect of peripheral 3-hydroxybutyrate injections on food intake and the contribution of the vagus nerve in the resista nce to dietary fat-induced obesity in a rodent model. S 5B/P1 rats, wh ich are resistant to dietary-fat induced obesity, and Osborne-Mendel r ats, which are sensitive; were adapted to reverse light cycle. Food in take was measured for 24 h following the injection of 3-hydroxybutyrat e, lactate, or glycerol (all 5 mMol/kg(0.75), SC) at the onset of dark . Three-hydroxybutyrate reduced food intake (p < 0.0001) in S 5B/P1 ra ts only. Lactate reduced food intake slightly (p < 0.009) in both stra ins and glycerol had no effect on food intake. In a second experiment, S 5B/P1 and Osborne-Mendel rats were adapted to a high-fat diet and w ere then subjected to either selective hepatic vagotomy or sham operat ion. Vagotomy had no effect on weight gain of Osborne-Mendel rats but allowed weight gain in S 5B/P1 rats (p < 0.0001). Even in vagotomized S 5B/P1 rats, however, blood 3-hydroxybutyrate levels were inversely a ssociated (r = -0.50) with food intake. These data suggest that the he patic vagus nerve may contribute to the resistance of S 5B/P1 rats to dietary-fat induced obesity, but the data do not rule out a strictly c entral role for the regulation of food intake by 3-hydroxybutyrate in this strain.