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 journalArticle

104 Citations (Scopus)

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 1 2003

Fingerprint

Human Mammary Glands
Lactation
Transgenic Mice
Milk
Lipids
Pregnancy
Breast
Epithelial Cells
Mouse mammary tumor virus
Human Adenoviruses
Lipid Metabolism
Viscosity
Epithelium
Fats
Biosynthesis
Weights and Measures
Glucose
Cell Line
Viruses
Tumors

Keywords

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

Cite this

Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation. / Schwertfeger, Kathryn L.; McManaman, James L.; Palmer, Carol A.; Neville, Margaret C.; Anderson, Steven M.

In: Journal of Lipid Research, Vol. 44, No. 6, 01.06.2003, p. 1100-1112.

Research output: Contribution to journalArticle

Schwertfeger, Kathryn L. ; McManaman, James L. ; Palmer, Carol A. ; Neville, Margaret C. ; Anderson, Steven M. / Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation. In: Journal of Lipid Research. 2003 ; Vol. 44, No. 6. pp. 1100-1112.
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