INCREASED EXPRESSION IN ADIPOCYTES OF OB RNA IN MICE WITH LESIONS OF THE HYPOTHALAMUS AND WITH MUTATIONS AT THE DB LOCUS

The gene product of the recently cloned mouse obese gene (ob) is impor tant in regulating adipose tissue mass, ob RNA is expressed specifical ly by mouse adipocytes in vivo in each of several different fat cell d epots, including brown fat, ob RNA is also expressed in cultured 3T3-4 42A preadipocyte cells that have been induced to differentiate, Mice w ith lesions of the hypothalamus, as well as mice mutant at the db locu s, express a 20-fold higher level of ob RNA in adipose tissue, These d ata suggest that both the db gene and the hypothalamus are downstream of the ob gene in the pathway that regulates adipose tissue mass and a re consistent with previous experiments suggesting that the db locus e ncodes the ob receptor, In db/db and lesioned mice, quantitative diffe rences in expression level of ob RNA correlated with adipocyte lipid c ontent. The molecules that regulate expression level of the ob gene in adipocytes probably are important in determining body weight, as are the molecules that mediate the effects of ob at its site of action.