Oberbauer A M, Stern J S, Johnson P R, Horwitz B A, German J B, Phinney S D, Beermann D H, Pomp D, Murray J D
Department of Animal Science, University of California, Davis, USA.
Growth Dev Aging. 1997 Fall-Winter;61(3-4):169-79.
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.
利用可调控的绵羊金属硫蛋白-绵羊生长激素（oMt1a-oGH）转基因，在雄性和雌性生长激素转基因（TG）小鼠中评估了42天暴露于升高的生长激素（GH）对脂肪组织的影响。在21日龄时激活转基因表达，随后在63日龄时使转基因表达失活（TG-on/off），增加了雄性和雌性个体的白色脂肪组织（WAT）储存库和全身脂质储存。以禁食体重的百分比表示的WAT，在野生型（WT）以及持续激活的TG雄性和雌性小鼠中，直至105日龄时并无差异，但在转基因失活后增加了约270%。相对于WT或TG动物，雄性和雌性TG +/-腹股沟储存库中的脂肪细胞数量更多。所导致的肥胖并未伴随着棕色脂肪组织产热能力的降低，以解偶联蛋白量为指标。生长激素转基因表达伴随着胰岛素水平升高，在转基因表达停止后恢复到WT水平（p>0.1）。早期短暂暴露于升高的生长激素使全身脂质增加近三倍，与性别无关；增加的脂质含量持续存在，反映了WAT肥大和增生。oMt1a-oGH小鼠提供了一种新型的诱导肥胖模型，该模型是由于撤除转基因刺激导致生长激素转基因失活而引起的。
