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A more recent version of this article appeared on July 1, 2007

Papers In Press, published online ahead of print April 23, 2007
J. Lipid Res., doi:10.1194/jlr.M600474-JLR200
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Submitted on October 26, 2006
Revised on March 15, 2007
Accepted on April 23, 2007

Developmental regulation of cytoplasmic lipid droplet accumulation in mammary epithelial cells: Roles of adipophilin and lipid metabolism

Tanya D. Russell, Carol A. Palmer, David J. Orlicky, Andreas Fischer, Michael C. Rudolph, Margaret C. Neville, and James L. McManaman

Obstetrics and Gynecology, University of Colorado Denver Health Sciences Center, Aurora, Colorado 80045

Corresponding Author: jim.mcmanaman{at}uchsc.edu

PAT proteins (perilipin, adipophilin, TIP47) are hypothesized to be critical regulators of lipid accumulation in eukaryotic cells. We investigated developmental relationships between the expression of these proteins and cytoplasmic lipid droplet (CLD) accumulation in differentiating secretory epithelial cells in mouse mammary glands. ADPH specifically localized to CLD in differentiating and lactating mammary glands and was found exclusively in the secreted lipid droplet fraction of mouse milk. ADPH transcripts were selectively detected in secretory epithelial cells, and steady-state levels of both ADPH mRNA and protein increased during secretory differentiation in patterns consistent with functional linkage to CLD accumulation. TIP47 also was detected in secretory epithelial cells; however it had a diffuse punctuate appearance and its mRNA and protein expression patterns did not correlate with CLD accumulation. Perilipin positive adipose cells and steady-state levels of perilipin mRNA and protein decreased during mammary gland differentiation suggesting a progressive loss of adipose lipid storage during this process. Collectively, these data demonstrate that increased ADPH expression is a specialized property of differentiated secretory epithelial cells and provide developmental evidence specifically linking increased ADPH expression to increased CLD accumulation. In addition, evidence is presented that the epithelial and adipose compartments of the mammary gland undergo concerted, developmentally regulated, shifts in lipid metabolism that increase the availability of fatty acids necessary for lipid synthesis by milk secreting cells.


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D. J. Orlicky, G. DeGala, C. Greenwood, E. S. Bales, T. D. Russell, and J. L. McManaman
Multiple functions encoded by the N-terminal PAT domain of adipophilin
J. Cell Sci., September 1, 2008; 121(17): 2921 - 2929.
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 J. Lipid Res.Home page
T. D. Russell, C. A. Palmer, D. J. Orlicky, E. S. Bales, B. H.-J. Chang, L. Chan, and J. L. McManaman
Mammary glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretion
J. Lipid Res., January 1, 2008; 49(1): 206 - 216.
[Abstract] [Full Text] [PDF]


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