Body composition of inactivated growth hormone (oMt1a-oGH) transgenic mice: 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 metallothionein- ovine GH (oMt1a-oGH) transgene in male and female GH transgenic (TG) mice. Activation of transgene expression at 21 d of age followed by inactivation of transgene expression at 63 d of age (TG-on/off) increased individual white adipose tissue (WAT) depots and total body lipid stores in both males and females. WAT, expressed as a percentage of fasted body weight, did not differ in wildtype (WT) and continuously activated TG males and females up to 105 d of age, but was increased approximately 270% following inactivation of the transgene. Inguinal depot adipocytes were more numerous in both male and female TG +/- relative to WT or TG animals. The ensuring obesity was not accompanied by a decrease in thermogenic capacity of brown adipose tissue, as indexed by uncoupling protein quantity. GH transgene expression was accompanied by elevated insulin levels that were restored to WT levels upon cessation of transgene expression (p > 0.1). Early, transient exposure to elevated GH increased total body lipid by nearly threefold independent of gender; the increased lipid content was sustained and reflected WAT hypertrophy and hyperplasia. The oMt1a-oGH mouse provides a novel model of induced obesity in response to inactivation of a GH-transgene by the withdrawal of the transgene stimulus.