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Nat Commun. 2018 Sep 4;9(1):3592. doi: 10.1038/s41467-018-05911-0.

Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT, 06520, USA.
2
Division of Endocrinology, Metabolism, and Diabetes, University of Colorado, Mail Stop F-8305; RC1 North, 12800 E. 19th Avenue P18-5107, Aurora, CO, 80045, USA.
3
WELBIO, Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles (ULB), 808, route de Lennik, BatC, C6-130, 1070, Brussels, Belgium.
4
Department of Population Sciences and Bekman Institute, City of Hope, 1500 East Duarte Rd., Duarte, CA, 91010, USA.
5
Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale University, 333 Ceder St., New Haven, CT, 06510, USA.
6
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University, 333 Ceder St., New Haven, CT, 06510, USA.
7
Department of Comparative Medicine, Yale University, 333 Ceder St., New Haven, CT, 06510, USA.
8
Department of Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect St., New Haven, CT, 06520, USA. valerie.horsley@yale.edu.
9
Department of Dermatology, Yale University, 333 Ceder St., New Haven, CT, 06510, USA. valerie.horsley@yale.edu.

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.

PMID:
30181538
PMCID:
PMC6123393
DOI:
10.1038/s41467-018-05911-0
[Indexed for MEDLINE]
Free PMC Article

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