Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation

Rachel K. Zwick, Michael C. Rudolph, Brett A. Shook, Brandon Holtrup, Eve Roth, Vivian Lei, Alexandra Keymeulen, Victoria Seewaldt, Stephanie Kwei, John Wysolmerski, Matthew S. Rodeheffer and Valerie Horsley ()
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Rachel K. Zwick: Yale University
Michael C. Rudolph: University of Colorado
Brett A. Shook: Yale University
Brandon Holtrup: Yale University
Eve Roth: Yale University
Vivian Lei: Yale University
Alexandra Keymeulen: Université Libre de Bruxelles (ULB)
Victoria Seewaldt: City of Hope
Stephanie Kwei: Yale University
John Wysolmerski: Yale University
Matthew S. Rodeheffer: Yale University
Valerie Horsley: Yale University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Adipocytes undergo pronounced changes in size and behavior to support diverse tissue functions, but the mechanisms that control these changes are not well understood. Mammary gland-associated white adipose tissue (mgWAT) regresses in support of milk fat production during lactation and expands during the subsequent involution of milk-producing epithelial cells, providing one of the most marked physiological examples of adipose growth. We examined cellular mechanisms and functional implications of adipocyte and lipid dynamics in the mouse mammary gland (MG). Using in vivo analysis of adipocyte precursors and genetic tracing of mature adipocytes, we find mature adipocyte hypertrophy to be a primary mechanism of mgWAT expansion during involution. Lipid tracking and lipidomics demonstrate that adipocytes fill with epithelial-derived milk lipid. Furthermore, ablation of mgWAT during involution reveals an essential role for adipocytes in milk trafficking from, and proper restructuring of, the mammary epithelium. This work advances our understanding of MG remodeling and tissue-specific roles for adipocytes.

Date: 2018
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DOI: 10.1038/s41467-018-05911-0

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