Regulation of Milk Lipid Formation and Secretion in the Mouse Mammary Gland
Cytosolic lipid droplets (CLDs), the immediate precursors of milk lipids in lactating animals, undergo cell-specific changes in their formation and intracellular distribution during mammary gland differentiation. Cell biological studies indicate that CLD formation in mammary epithelial cells is regulated in part by AKT-dependent increases in glucose uptake. Proteomic studies show that CLDs from lactating mammary epithelial cells possess a distinct protein composition enriched in molecules involved in their secretion and intracellular transport. CLD secretion is dependent on lactation and requires the purine catabolic enzyme xanthine oxidoreductase (XOR). Confocal immunofluorescence microscopy of XOR in lactating and nonlactating mammary glands and biochemical analysis of secreted CLDs link the secretion process to the formation of a stable tripartite complex between XOR, adipophilin (ADPH), and butyrophilin (Btn). Together these studies provide a molecular and cellular framework for understanding the process of milk lipid formation.
KeywordsCholesterol Lactate Pyruvate Luminal Lime
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- Baldwin RL, Yang YT. Enzymatic and metabolic changes in the development of lactation. In: Larson BL, Smith VR, editors. Lactation. New York: Academic Press, 1974; pp 349–407.Google Scholar
- Dils RR. Milk fat synthesis. In: Mepham TB, editor. Biochemistry of Lactation. Amsterdam: Elsevier, 1983; pp 141–157.Google Scholar
- Fleet IR, Goode JA, Hamon MH, Laurie MS, Linzell JL, Peaker M. Secretory activity of goat mammary glands during pregnancy and the onset of lactation. J Physiol 1975;251:763–773.Google Scholar
- Hollman KH. Cytology and fine structure of the mammary gland. In: Larson BL, Smith VR, editors. Lactation. New York: Academic Press, 1974; pp 3–95.Google Scholar
- Lund LR, Romer J, Thomasset N, Solberg H, Pyke C, Bissell MJ, Dano K, Werb Z. Two distinct phases of apoptosis in mammary gland involution: Proteinase-independent and -dependent pathways. Development 1999;122:181–193.Google Scholar
- Miura S, Gan JW, Brzostowski J, Parisi MJ, Schultz CJ, Londos C, Oliver B, Kimmel AR. Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. J Biol Chem 2002;277:32253–32257.PubMedCrossRefGoogle Scholar
- Neville MC, Neifert MR, editors. Lactation: Physiology, Nutrition, and Breast-Feeding. New York: Plenum Press, 1983.Google Scholar
- Souza SC, Muliro KV, Liscum L, Lien P, Yamamoto MT, Schaffer JE, Dallai GE, Wang X, Kraemer FB, Obin M, Greenberg AS. Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system. J Biol Chem 2002;277:8267–8272.PubMedCrossRefGoogle Scholar
- Wellings SR. Ultrastructural basis of lactogenesis. In: Reynolds M, Folley SJ, editors. Lactogenesis. Philadelphia: University of Pennsylvania Press, 1969; pp 5–25.Google Scholar