Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity.
Beige and brown adipocytes generate heat in response to reductions in ambient temperature. When warmed, both beige and brown adipocytes exhibit morphological "whitening," but it is unknown whether or to what extent this represents a true shift in cellular identity. Using cell-type-specific profiling in vivo, we uncover a unique paradigm of temperature-dependent epigenomic plasticity of beige, but not brown, adipocytes, with conversion from a brown to a white chromatin state. Despite this profound shift in cellular identity, warm whitened beige adipocytes retain an epigenomic memory of prior cold exposure defined by an array of poised enhancers that prime thermogenic genes for rapid response during a second bout of cold exposure. We further show that a transcriptional cascade involving glucocorticoid receptor and Zfp423 can drive warm-induced whitening of beige adipocytes. These studies identify the epigenomic and transcriptional bases of an extraordinary example of cellular plasticity in response to environmental signals.
|Year of Publication||
2018 May 01
|PubMed Central ID||
R01 DK085171 / DK / NIDDK NIH HHS / United States
R01 DK102173 / DK / NIDDK NIH HHS / United States
P30 DK046200 / DK / NIDDK NIH HHS / United States
R01 DK104789 / DK / NIDDK NIH HHS / United States
R01 DK113669 / DK / NIDDK NIH HHS / United States
R01 DK102170 / DK / NIDDK NIH HHS / United States