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Papers In Press, published online ahead of print April 16, 2003
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University of Colorado Health Sciences Center, Denver, CO 80262
Corresponding Author: Steve.Anderson{at}uchsc.edu
We and others have shown previously that expression of a constitutively activated mutant of Akt in the mammary glands of transgenic mice results in a delay in changes associated with post-lactational involution (1-3). In this paper, we report that precocious lipid accumulation in the alveolar epithelium of MMTV-myr-Akt transgenic mice is accompanied by a lactation defect characterized by a 50% decrease in litter weight over the first nine days of lactation. Although ductal structures and alveolar units appeared to develop normally during pregnancy, cytoplasmic lipid droplets appeared precociously in mammary epithelial cells in early pregnancy along with increased expression of the protein adipophilin (ADPH), which is associated with lipid droplets. By late pregnancy the lipid droplets had become significantly larger than in non-transgenic mice. These large cytoplasmic lipid droplets persisted into lactation. The fat content of milk collected from lactating myr-Akt transgenic mice was increased to 65-70% milk fat from the 25-30% observed in the wild type mice. These data suggest that 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, in addition to its role in apoptosis in the mammary gland, Akt plays an important role in regulation of lipid metabolism.
Revised on April 2, 2003
Accepted on April 2, 2003
Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation
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