EFFECTS OF ANTIBODIES TO ADIPOCYTES ON BODY-WEIGHT, FOOD-INTAKE, AND ADIPOSE-TISSUE CELLULARITY IN OBESE RATS

Female Wistar rats mere fed on a high fat diet for 18 weeks, during wh ich their energy intake increased by 25% and body weight by 50% due to a doubling of adipose tissue tissue stores. Animals were then treated with increasing doses of a sheep polyclonal antiserum to rat adipocyt es on days 1-4 and 7 after which they remained untreated for 14 weeks. Antibody treatment reduced body weight by 10% and the weight of param etrial and subcutaneous adipose tissue by 30-40%, This decrease was ex plicable entirely in terms of a decrease in the number of adipocytes p resumably due to adipocyte lysis, These favourable changes in body fat mass were accompanied by improvement in at least one metabolic factor associated with obesity-serum leptin concentrations were significantl y reduced in treated animals compared with high fat controls. Genetica lly obese Zucker rats also showed decreases in the number of adipocyte s after treatment with antibodies but in contrast to diet-induced obes e rats, they showed a compensatory increase in adipocyte volume which attenuated the effects on body fat mass. These results demonstrate for the first time, the potential to treat diet-induced obesity with anti bodies to adipocytes by producing longterm reductions in the number of adipocytes, with minimal side-effects. (C) 1998 Academic Press.