转基因和基因敲除内脂素对小鼠脂肪积累的对比研究

目的内脂素(visfatin)也被叫做尼克酰胺磷酸核糖基转移酶,是一种脂肪因子,研究表明其与肥胖有关,但是与脂肪积累的关系仍然不明确,本研究是以内脂素转基因和内脂素基因敲除杂合子小鼠为对象,研究内脂素与脂肪积累的关系。方法 Western blot法对比分析转基因、基因敲除杂合子和野生型小鼠脂肪组织中内脂素表达水平。从2月龄开始对3种雌性小鼠饲喂高脂饲料,分别在2、4、6、8、9月龄测定其体重变化,并在9月龄时利用磁共振成像定性观测小鼠脂肪积累及分布,称量皮下和腹腔脂肪总重量并对腹腔脂肪组织进行组织学观察。结果内脂素转基因小鼠脂肪组织中内脂素的表达量比野生小鼠增加37%,基因敲除杂合子小鼠比野生小鼠降低了55%。饲喂7个月高脂饲料后,转基因小鼠体重平均27.8±0.8 g,野生小鼠体重平均33.6±1.1 g,基因敲除杂合子小鼠体重平均37.6±1.9 g。皮下和腹腔脂肪总重量测定结果显示转基因小鼠的脂肪总重量比野生小鼠降低了40%,基因敲除杂合子小鼠的脂肪总重量比野生小鼠增加了37%,组织学染色显示,内脂素转基因小鼠的平均单个脂肪细胞面积最小,而基因敲除杂合子小鼠面积最大。结果证实,内脂素表达量与体重、皮下和内脏脂肪总重量及脂肪细胞大小呈负相关。结论在饲喂高脂饲料的情况下,内脂素可以抑制脂肪的积累。

The comparative research of visfatin transgenic mice and knockout visfatin( /-) mice in accumulation of adipose tissue

Abstract] Objective Visfatin(also known as nicotinamide phosphoribosyltransferase or Nampt)is an adipokine associated with obesity ,but the relationship is unclear. The aim of the present study was to determine whether fat accumulation was related to visfatin level. Methods The expression levels of visfatin were detected with western blot from the adipose tissues of visfatin transgenic mice, wild type mice and knockout visfatin( /-) mice. The female mice were feed a high fat diet from 2 to 9 months of age. The body weight was recorded at 2, 4, 6, 8, 9 months of age. Then the mice were sacrificed at 9 months of age and the total weight of subcutaneous and visceral adipose tissue was scaled. The histopathology of visceral adipose tissue was observated under light microscope. Results The expression of visfatin in transgenic mice increased by 37% compared with that of wild type mice due to the transgenic expression of visfatin, while the expression level of visfatin in visfaitn( /-) mice decreased by 55% compared with that of wild type mice due to the one copy gene knockout of visfatin. After high fat diet for 7 months, the average body weight of visfatin transgenic mice was 27.8?.8g, wild type mice was 33.6?.1g and the konckout visfatin( /-) mice was 37.6g?.9g. The total weight of subcutaneous and visceral adipose tissue in visfatin transgenic mice decreased by 40% compared with that of wild type mice while knockout visfatin( /-) mice increased by 37% compared with that of wild type mice. Histopathology observation showed that visfatin transgenic mice had smallest size of visceral adipose cell and knockout visfatin( /-) mice had biggest size of visceral adipose cell. Our results indicated that the visfatin level in mice exhibited a negative effect on body weight, the total weight of subcutaneous and visceral adipose tissue, the size of visceral adipose cell. Conclusions our resulted suggested that the accumulation of adipose tissue was restrained by visfatin when mice were fed a high fat diet.