BODY-COMPOSITION OF INACTIVATED GROWTH-HORMONE (OMT1A-OGH) TRANSGENICMICE - GENERATION OF AN OBESE PHENOTYPE

The consequences of a 42 d exposure to elevated growth hormone (GH) on adipose tissue were assessed using the regulatable ovine metallothion ein-ovine GH (oMt1a-oGH) transgene in male and female GH transgenic (T G) mice. Activation of transgene expression at 21 d of age followed by inactivation of transgene expression at 63 d of age (TG-on/off) incre ased individual white adipose tissue (WAT) depots and total body lipid stores in both males and females. WAT, expressed as a percentage of f asted body weight, did not differ in wildtype (WT) and continuously ac tivated TG males and females up to 105 d of age, but was increased app roximately 270% following inactivation of the transgene. Inguinal depo t adipocytes were more numerous in both male and female TG+/- relative to WT or TG animals. The ensuing obesity was not accompanied by a dec rease in thermogenic capacity of brown adipose tissue, as indexed by u ncoupling protein quantity. GH transgene expression was accompanied by elevated insulin levels that were restored to WT levels upon cessatio n of transgene expression (p > 0.1). Early, transient exposure to elev ated GH increased total body lipid by nearly threefold independent of gender; the increased lipid content was sustained and reflected WAT hy pertrophy and hyperplasia. The oMt1a-oGH mouse provides a novel model of induced obesity in response to inactivation of a GH-transgene by th e withdrawal of the transgene stimulus.