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Journal of Lipid Research, Vol. 44, 1100-1112, June 2003
Copyright © 2003 by Lipid Research, Inc.
Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation
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* Departments of Pathology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262
Obstetrics and Gynecology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262
Physiology and Biophysics, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262
** Program in Molecular Biology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262
2 To whom correspondence should be addressed. e-mail: steve.anderson{at}uchsc.edu
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.
Abbreviations: ADPH, adipophilin; GLUT1, glucose transporter-1; MMTV, mouse mammary tumor virus; WAP, whey acidic protein; WGA, wheat germ agglutinin
Supplementary key words transgenic mice • glucose transport • milk fat globule • lipid biosynthesis
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