Schwertfeger Kathryn L, McManaman James L, Palmer Carol A, Neville Margaret C, Anderson Steven M
Departments of Pathology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
J Lipid Res. 2003 Jun;44(6):1100-12. doi: 10.1194/jlr.M300045-JLR200. Epub 2003 Apr 16.
Expression of constitutively activated Akt in the mammary glands of transgenic mice results in a delay in post-lactational involution. We now report precocious lipid accumulation in the alveolar epithelium of mouse mammary tumor virus-myr-Akt transgenic mice accompanied by a lactation defect that results in a 50% decrease in litter weight over the first 9 days of lactation. Although ductal structures and alveolar units develop normally during pregnancy, cytoplasmic lipid droplets appeared precociously in mammary epithelial cells in early pregnancy and were accompanied by increased expression of adipophilin, which is associated with lipid droplets. By late pregnancy the lipid droplets had become significantly larger than in nontransgenic mice, and they persisted into lactation. The fat content of milk from lactating myr-Akt transgenic mice was 65-70% by volume compared to 25-30% in wild-type mice. The diminished growth of pups nursed by transgenic mothers could result from the high viscosity of the milk and the inability of the pups to remove sufficient quantities of milk by suckling. Transduction of the CIT3 mammary epithelial cell line with a recombinant human adenovirus encoding myr-Akt resulted in an increase in glucose transport and lipid biosynthesis, suggesting that Akt plays an important role in regulation of lipid metabolism.
在转基因小鼠的乳腺中组成型激活的Akt的表达导致哺乳期后退化延迟。我们现在报告，在小鼠乳腺肿瘤病毒-myr-Akt转基因小鼠的肺泡上皮中出现早熟的脂质积累，并伴有泌乳缺陷，导致在泌乳的前9天幼崽体重下降50%。尽管在怀孕期间导管结构和肺泡单位正常发育，但在怀孕早期乳腺上皮细胞中早熟地出现了细胞质脂滴，并伴有与脂滴相关的脂肪分化相关蛋白表达增加。到怀孕后期，脂滴变得比非转基因小鼠中的明显更大，并持续到哺乳期。与野生型小鼠中25%-30%的体积相比，泌乳的myr-Akt转基因小鼠的乳汁脂肪含量按体积计为65%-70%。由转基因母亲哺育的幼崽生长减缓可能是由于乳汁的高粘度以及幼崽无法通过哺乳摄取足够量的乳汁所致。用编码myr-Akt的重组人腺病毒转导CIT3乳腺上皮细胞系导致葡萄糖转运和脂质生物合成增加，表明Akt在脂质代谢调节中起重要作用。
