Adipo-epithelial transdifferentiation: old data and new perspectives

White and brown adipose tissues are organized to form a true organ. White adipose tissues store energy that is provided to the organism in the intervals between meals and brown adipose tissues burn lipids to produce heat. When the cold exposure is chronic, white converts into brown (browning) to help thermogenesis and when the energy balance is chronically positive, brown converts into white (whitening) to help store energy. The plastic property of the adipose organ also allows a reversible formation of milk-producing alveolar cells in the mammary fat during pregnancy and lactation (pinking, because the organ is pink during pregnancy). This last striking property of the adipose organ is challenged by other authors, but our data, based on morphology (including electron microscopy), immunohistochemistry, lineage tracing, explants, and in vitro data described here, support this phenomenon. Our experiments, including microarray data comparing cleared fat pad with normal glands in pregnant mice, allowed us to detect four molecular players in the pinking phenomenon: E74-like ETS transcription factor (ELF5), osteopontin, GATA binding protein 3 (GATA3), and Mir200c. Another molecular player could be the parathyroid hormone-related protein (PTHrP). Mice lacking each of these molecules have impaired alveologenesis during pregnancy. Finally, several data seem to suggest a strong functional relationship between the onco-suppressor gene breast cancer gene 1 (BRCA1) and the reversible adipo-epithelial transdifferentiation phenomenon, opening new avenues for future studies in the connection between pinking and breast cancer.