出版社:American Society for Biochemistry and Molecular Biology
摘要:PAT proteins (perilipin, adipophilin, and TIP47) are hypothesizedto be critical regulators of lipid accumulation in eukaryoticcells. We investigated the developmental relationships betweenthe expression of these proteins and cytoplasmic lipid droplet(CLD) accumulation in differentiating secretory epithelial cellsin mouse mammary glands. Adipophilin (ADPH) specifically localizedto CLD in differentiating and lactating mammary glands and wasfound exclusively in the secreted lipid droplet fraction ofmouse milk. ADPH transcripts were selectively detected in secretoryepithelial cells, and steady-state levels of both ADPH mRNAand protein increased during secretory differentiation in patternsconsistent with functional linkage to CLD accumulation. TIP47also was detected in secretory epithelial cells; however, ithad a diffuse punctate appearance, and its mRNA and proteinexpression patterns did not correlate with CLD accumulation.Perilipin-positive adipose cells and steady-state levels ofperilipin mRNA and protein decreased during mammary gland differentiation,suggesting a progressive loss of adipose lipid storage duringthis process. Collectively, these data demonstrate that increasedADPH expression is a specialized property of differentiatedsecretory epithelial cells and provide developmental evidencespecifically linking increased ADPH expression to increasedCLD accumulation. In addition, evidence is presented that theepithelial and adipose compartments of the mammary gland undergoconcerted, developmentally regulated shifts in lipid metabolismthat increase the availability of fatty acids necessary forlipid synthesis by milk-secreting cells.Supplementary key words perilipin • mammary gland • adipose • fatty acid • cytoplasmic lipid droplet • differentiation • triglyceride