THE PAPER
Q.A. Wang et al., “Reversible de-differentiation of mature white
adipocytes into preadipocyte-like precursors during lactation,” Cell,
28:P282–88.E3, 2018.Breast tissue undergoes a remarkable transformation to allow for
breastfeeding—and the process reverses after weaning. Lipid-filled
fat cells essentially disappear to make room for milk production, and
once an animal is done lactating, the cells come back again.
While the phenomenon of the disappearing-reappearing fat cell is
well documented, the fate of these cells, called adipocytes, during the
cycle was a subject of debate. Do the cells die off, or turn into another
cell type? And in either scenario, how do they make a comeback after
lactation ceases?
To find out, Philipp Scherer’s group at the University of Texas
Southwestern Medical Center took advantage of the lab’s AdipoChaser
mouse, in which mature fat cells that are stained blue retain their color
permanently. The investigators found that during pregnancy and lac-
tation, these big, blue fat cells shed their lipids, change shape, and
become much, much smaller. “Morphologically, it’s a very dramatic
alteration,” says coauthor Annabel Wang, a former postdoc of Scherer
who now runs her own lab at City of Hope, a hospital and research
center in California.
The adipocytes also change their gene expression and identity:
Wang’s analysis of single-cell RNA sequencing indicates they de-
differentiate into fat-cell precursors. Then, when the mammary
tissue reverts to its pre-pregnancy configuration as the pups wean,
these precursors give rise to differentiated adipocytes.
“All the fat cells in the regenerated fat are labeled in the original
color,” says Scherer, indicating that they don’t die off, nor do they trans-
differentiate from milk-producing cell types, as other scientists had
proposed. The researchers watched this shrinkage and expansion of
the blue-colored cells over several cycles of pregnancy and lactation.
Shortly after Wang published her results this summer, Valerie
Horsley’s team at Yale University reported complementary observa-
tions. In mice, the researchers found, fat cells shrink by losing lipids
to make room for milk-producing tissue, then regain their composi-
tion when that epithelial tissue recedes (Nat Commun, 9:3592, 2018).
Horsley and her colleagues also discovered that the fat cells, as they’re
bulking up again, pull lipids from those regressing milk-producing
cells. “It’s kind of recycling the milk, which is really cool,” Horsley says.
“Both papers seem to have settled the long-standing ques-
tion of whether adipocytes disappear during pregnancy and lacta-tion or remain present during these phases as smaller, compressed
cells,” says Jane Visvader, the joint head of the Breast Cancer Labo-
ratory at the Walter and Eliza Hall Institute of Medical Research in
Australia, in an email to The Scientist.
What isn’t settled are the signals that control adipocytes’ shape-
shifting, both upon losing lipids and regaining them. “We wish we
knew,” says Scherer. “That will be now the next obvious step, trying to
identify what these factors actually are.” —Kerry Grens © IKUMI KAYAMA, STUDIO KAYAMA52 THE SCIENTIST | the-scientist.com
The Literature
EDITOR’S CHOICE PAPERSADIPOCYTE RECYCLING MODEL: Before pregnancy 1 , mouse mammary
tissue contains large fat cells filled with lipids. To follow the adipocytes’ fate
through lactation, researchers stained them blue. During breastfeeding 2 , these
labeled cells lose their lipids and shrink dramatically. They also show signs of
reprogramming to a precursor state. After lactation 3 , when milk-producing cells
die off in a process called involution, these same blue cells fill back up with lipids
and redifferentiate into adipocytes.Adipocyte
precursorRedifferentiated
adipocyteFEMALE MOUSEAdipocyteMilk-producing
cellsCELL & MOLECULAR BIOLOGYMake Room for Milk
Doxycycline that induces adipocyte labelingLipidsMAMMARY TISSUE