Autoimmunization against beta-endorphin increases food intakes and body weights of obese rats.

Opioid peptides in the brain are postulated to mediate the hunger component of the control of food intake and regulation of body weight and concentrations are increased in the pituitaries of genetically obese rodents. However, systemic increases in opioids have been associated with satiety. Thus a chronic decrease in systemic concentrations of the opioid beta-endorphin induced by autoimmunization was predicted to increase food intake and body weight. Zucker obese (n = 20, 568 +/- 13 g) and lean (n = 20, 299 +/- 16 g) rats were autoimmunized against bovine serum albumin (BSA) or BSA conjugated to beta-endorphin (BSA-BE). Eight weeks after immunization serum from BSA-BE rats bound at least 7 times the circulating concentration of beta-endorphin. Food intakes were greater in BSA-BE obese (31.7 vs. 30.4 g/day, p less than 0.001) and lean rats (21.4 vs. 21.0 g/day, p less than 0.007) during weeks 5-8 and only obese rats, weeks 9-12 (31.8 vs. 30.3 g/day, p less than 0.009). Body weight gains were greater for BSA-BE than BSA obese rats during weeks 1-4 (1.34 vs. 0.92 g/day, p less than 0.05) and 9-12 (0.95 vs. 0.43 g/day, p less than 0.01). At 8 weeks the plasma concentrations of "free" beta-endorphin were decreased 78% (34 vs. 154 pmol/l, p less than 0.001) and "total" ("free" plus antibody-bound) beta-endorphin were increased (427 vs. 101 pmol/l, p less than 0.001). These results suggest that systemic concentrations of beta-endorphin may play an important role in the control of food intake and regulation of energy balance.