The undernourished rat pup and brown adipose tissue : a proposed model for the study of anorexia nervosa

Abstract

Anorexia nervosa is a disorder of unknown etiology, which presents itself as self-induced starvation and accompanying severe weight loss. This condition has a 1% morbidity, with an estimated mortality of 5-25%. No references have been found which investigate the possible role of brown adipose tissue (BAT) in anorexia nervosa. It is well established that BAT functions as a thermogenic effector during cold exposure, and recent investigations have suggested that it might be involved in weight regulation in humans, as well as rodents. Victims of anorexia nervosa who submit themselves for treatment often experience great difficulty in increasing their body weight and maintaining it at a normal level. It was proposed that anorexics exhibit increased levels of BAT thermogenesis in response to the reduction of body temperature, resulting from loss of both the shivering response to cold and insulating layers of white adipose tissue. The metabolic consequences of increased BAT thermogenesis, further augmented by amphetamine abuse and hyperactivity, could contribute to failure of recovery. Since BAT thermogenesis is a sympathetically mediated response, it was proposed that chronic beta adrenoceptor blockade would prevent this counterproductive energy loss and promote recovery of lost body weight. Postnatally undernourished male and female rat pups were used as a model system and subjected to chronic beta adrenergic blockade with daily intraperitoneal injections of nadolol (20 mg/kg ip) during a 28-day re-feeding period. Controls received equivalent doses of isotonic saline solution. Body weight, water and food intake, and body composition were the variables used to assess effects of the drug treatment. Analysis of variance indicated that chronic beta adrenoceptor blockade with nadolol did not reverse the effects of postnatal undernutrition and, in fact, caused further reductions in weight gain of all animals, regardless of sex or diet. It was concluded that the profound growth retardation imposed by postnatal undernutrition made these young rats an unsuitable model system to test the use of nadolol as an adjunct therapy in the treatment of anorexia nervosa.