title: Cytoplasmic lipid droplet accumulation in developing mammary epithelial cells: roles of adipophilin and lipid metabolism.
abstract: PAT proteins (perilipin, adipophilin, and TIP47) are hypothesized to be critical regulators of lipid accumulation in eukaryotic cells. We investigated the developmental relationships between the expression of these proteins and cytoplasmic lipid droplet (CLD) accumulation in differentiating secretory epithelial cells in mouse mammary glands. Adipophilin (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 punctate 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.
authors: Graduate Programs in Molecular Biology, Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Aurora, CO, USA.
authors: Tanya D
authors: TD
authors: Russell
authors: Carol A
authors: CA
authors: Palmer
authors: David J
authors: DJ
authors: Orlicky
authors: Andreas
authors: A
authors: Fischer
authors: Michael C
authors: MC
authors: Rudolph
authors: Margaret C
authors: MC
authors: Neville
authors: James L
authors: JL
authors: McManaman
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D007774:Lactation; D050356:Lipid Metabolism / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D000070778:Perilipin-1; D000070780:Perilipin-2; D000070796:Perilipin-3; D010750:Phosphoproteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D000070778:Perilipin-1; D000070780:Perilipin-2; D000070796:Perilipin-3; D010750:Phosphoproteins; C000602983:Plin2 protein, mouse; C523440:Plin3 protein, mouse