Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation

Kathryn L. Schwertfeger, James L. McManaman, Carol A. Palmer, Margaret C. Neville, Steven M. Anderson

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1100-1112
Number of pages13
JournalJournal of lipid research
Volume44
Issue number6
DOIs
StatePublished - Jun 2003

Keywords

  • Glucose transport
  • Lipid biosynthesis
  • Milk fat globule
  • Transgenic mice

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