Rødgaard Tina, Skovgaard Kerstin, Stagsted Jan, Heegaard Peter M H
Innate Immunology Group, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark.
Cell Reprogram. 2013 Jun;15(3):185-94. doi: 10.1089/cell.2012.0091. Epub 2013 May 13.
The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.
本研究的目的是评估克隆猪作为反映肥胖相关先天免疫因子基因表达谱变化的猪肥胖模型的实用性。分析了瘦肉型和饮食诱导肥胖型克隆家猪的肝脏和脂肪组织中43种先天免疫基因的表达以及六种免疫因子的血清浓度,并与正常家猪(肥胖型和瘦肉型)进行比较。克隆动物中受肥胖影响的基因数量低于对照动物。克隆猪脂肪组织中所有受肥胖影响的基因均下调;而对照动物中既有上调也有下调。克隆导致脂肪组织表达模式的分化程度较低。最后,与肥胖对照以及瘦肉型克隆猪和对照相比,肥胖克隆猪中两种急性期蛋白(APPs),即触珠蛋白(HP)和血清类粘蛋白(ORM)的血清浓度升高。一般来说,与正常同胞相比,克隆同胞个体之间的表型差异并未减少。因此,我们得出结论,克隆既限制了对肥胖作出反应的基因数量,也限制了组织分化基因表达的程度,同时仅在克隆肥胖猪中出现急性期蛋白血清浓度升高。这可能表明,如本研究所述,肥胖克隆猪中出现的急性期蛋白反应是克隆猪对肥胖特征性基因反应偏斜的结果。在将克隆动物用作肥胖先天反应模型时应考虑到这一点。