Program in Molecular Medicine; Graduate School of Biomedical Sciences
Cell Biology | Cells | Cellular and Molecular Physiology | Lipids | Physiological Processes
Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate SNFs, and require adipocyte cyclic AMP/protein kinase A (cAMP/PKA) signaling for beige adipocyte appearance, as it is blocked by adipocyte Gsalpha deficiency. Surprisingly, however, in contrast to cold-exposed mice, neither iWAT denervation nor Nrg4 loss attenuated adipocyte browning in iAdFASNKO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type in iAdFASNKO mice, and their depletion abrogated iWAT beiging. Altogether, these findings reveal that divergent cellular pathways are sufficient to cause adipocyte browning. Importantly, adipocyte signaling to enhance alternatively activated macrophages in iAdFASNKO mice is associated with enhanced adipose thermogenesis independent of the sympathetic neuron involvement this process requires in the cold.
beige adipocytes, de novo lipogenesis, macrophage polarization, stromal vascular fraction, sympathetic nerve fibers
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Copyright 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Henriques F, Bedard AH, Guilherme A, Kelly M, Chi J, Zhang P, Lifshitz LM, Bellvé K, Rowland LA, Yenilmez B, Kumar S, Wang Y, Luban J, Weinstein LS, Lin JD, Cohen P, Czech MP. Single-Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis. Cell Rep. 2020 Aug 4;32(5):107998. doi: 10.1016/j.celrep.2020.107998. PMID: 32755590; PMCID: PMC7433376. Link to article on publisher's site
Henriques F, Bedard AH, Guilherme AL, Kelly M, Lifshitz LM, Bellve KD, Rowland LA, Yenilmez B, Kumar S, Wang Y, Luban J, Czech MP. (2020). Single-Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.celrep.2020.107998. Retrieved from https://escholarship.umassmed.edu/oapubs/4321
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