Program in Molecular Medicine; Graduate School of Biomedical Sciences
Biochemistry | Biological Phenomena, Cell Phenomena, and Immunity | Cell Biology | Cellular and Molecular Physiology | Lipids | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Physiological Processes
The “browning” of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF activity. Thus, the strong induction of thermogenic adipocytes prompted by deletion of adipocyte fatty acid synthase (iAdFASNKO mice) was unaffected by denervation or the deletion of SNF modulator Neuregulin-4. However, browning of iWAT in iAdFASNKO mice does require adipocyte cAMP/protein kinase A signaling, as it was blocked in adipocyte- selective Fasn/Gsα double KO mice. Single-cell transcriptomic analysis of iAdFASNKO mouse adipose stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type. Mechanistically, depletion of such phagocytic immune cells in iAdFASNKO mice fully abrogated appearance of thermogenic adipocytes in iWAT. Altogether, these findings reveal an unexpected pathway of cAMP/PKA-dependent iWAT browning that is initiated by adipocyte signals and caused by macrophage-like cells independent of sympathetic neuron involvement.
beige adipocytes, de novo lipogenesis, sympathetic nerve fibers, stromal vascular fraction, macrophage polarization
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 2020.05.04.077529; doi: https://doi.org/10.1101/2020.05.04.077529. Link to preprint on bioRxiv service.
Henriques F, Bedard AH, Guilherme AL, Kelly M, Lifshitz LM, Bellve KD, Rowland L, Yenilmez B, Kumar S, Wang Y, Luban J, Czech MP. (2020). Single Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.05.04.077529. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1682
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