While obesity is considered to be the major nutritional disorder in the United States and in many parts of the industrialized world, our understanding of the basic mechanisms involved in this disease is still far from complete. Among the hypotheses entertained to explain a certain percentage of obese individuals is the concept that a relatively mild infection of the central nervous system might cause perturbations in the pituitary-hypothalamus axis leading to abnormalities in the satiety centers and subsequently obesity. Support for this concept has been our recent discovery that CNS infection of mice with canine distemper virus (CDV) results in massive obesity in approximately 25% of the survivors of the infection. Germane to this proposal has been the observation that routine histological sections of the brains of these animals fails to reveal any abnormalities. Further exploration of these findings will be to pursue studies in both animals and humans. Experimentally we wish to explore the relationship of the possible persistence of viral antigens in specific areas of the brain and whether or not serum antibodies or fixed antibodies are involved in the areas of presumed pathological damage. This will be correlated with structural analysis of the neurological tracts in the hypothalamic area. Finally we will attempt to determine whether genetic variations in our animals predispose to the virally induced obesity. In the human we plan to concentrate on whether 1) there is any evidence for CNS pathology in the brains of obese individuals using more sophisticated histological methods to detect CNS pathology; 2) to determine whether the HLA antigenic makeup of the individual contributes or predisposes to obesity.
