Sustained hyperleptinemia in normal rats induced by infusing a recombinant adenovirus containing the rat leptin cDNA (AdCMV-leptin) exhibited a remarkable reduction in food intake (AdCMV-leptin, 9.3 +/-2.6 vs untreated, 20.6 +/- 1.0 g/day) and ablated body fat without any significant changes in wet weight of liver and left ventricle. In those hyperleptinemic rats, we found a 52% reduction in wet weight of salivary gland compared with that in the pair-fed AdCMV-beta-gal-treated rats, which received a recombinant virus containing the beta-galactosidase gene (AdCMV-beta-gal) and were fed on the same amount of food as had been consumed by the AdCMV-leptin-treated group on the previous day. Microscopic examination with hematoxylin-eosin staining revealed that atrophic change was induced in both serous and mucous gland only in the AdCATV-leptin-treated group, but not in the pair-fed controls. Thus, the atrophic changes in hyperleptinemic rats were due to neither a decrease of food intake nor disuse of the salivary gland related with anorexia. Our data suggested that size of the salivary gland was controlled, at lease in part, by "nonanorexic" effect of leptin. (C) 2002 Elsevier Science (USA).