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 Gsα 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.
- MeSH
- aktivace makrofágů MeSH
- AMP cyklický metabolismus MeSH
- analýza jednotlivých buněk * MeSH
- béžové tukové buňky metabolismus MeSH
- bílá tuková tkáň metabolismus MeSH
- denervace MeSH
- fenotyp MeSH
- hnědá tuková tkáň metabolismus MeSH
- makrofágy metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- neureguliny nedostatek metabolismus MeSH
- nízká teplota MeSH
- polarita buněk MeSH
- RNA metabolismus MeSH
- signální transdukce * MeSH
- syntázy mastných kyselin metabolismus MeSH
- termogeneze * MeSH
- uncoupling protein 1 genetika metabolismus MeSH
- upregulace genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
