OBESE GENE-EXPRESSION AT IN-VIVO LEVELS BY FAT PADS DERIVED FROM SC IMPLANTED 3T3-F442A PREADIPOCYTES

3T3-F442A preadipocytes implanted s,c, into athymic mice develop into fat pads that are indistinguishable from normal adipose tissue, Implan ted preadipocytes harboring a P-galactosidase transgene gave rise to f at Dads in which almost all adipocytes expressed P-galactosidase. This Finding proved that the implanted 3T3-F442A preadipocytes, rather tha n endogenous preadipose cells, gave rise to the newly developed ''adip ose tissue.'' 3T3-F442A preadipocytes, when differentiated into adipoc ytes in cell culture, express the obese gene at an unexpectedly low le vel, i.e., less than or equal to 1% the level in adipose tissue, Howev er, adipose tissue derived from s,c. implanted 3T3-F442A preadipocytes expressed leptin mRNA at a level comparable to that in epididymal adi pose tissue, These findings indicate that a factor(s) or condition, pr esent in the tissue context and necessary for maximal obese gene expre ssion, is lacking in cell culture, Furthermore, adipocytes derived fro m the implanted cells were hormonally responsive in that leptin mRNA l evels were up-regulated 3- to S-fold by glucocorticoid injection into the host animal. Thus, these findings indicate that adipose-specific p romoter-reporter constructs, transfected into 3T3-F442A preadipocytes, can be tested in an in vivo context during and after development of t hese cells into adipose tissue, Furthermore, the effect of transgenes on the adipogenic development of the implanted preadipocytes can be as sessed, Thus, this approach offers a faster and less costly alternativ e to the transgenic mouse method for assessing adipose gene function.