University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine; Graduate School of Biomedical Sciences
Publication Date
2020-05-05
Document Type
Article Preprint
Disciplines
Biochemistry | Biological Phenomena, Cell Phenomena, and Immunity | Cell Biology | Cellular and Molecular Physiology | Lipids | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Physiological Processes
Abstract
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.
Keywords
beige adipocytes, de novo lipogenesis, sympathetic nerve fibers, stromal vascular fraction, macrophage polarization
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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
10.1101/2020.05.04.077529
Source
bioRxiv 2020.05.04.077529; doi: https://doi.org/10.1101/2020.05.04.077529. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
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
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Biochemistry Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Lipids Commons, Molecular Biology Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Physiological Processes Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.