Skip to main content
. Author manuscript; available in PMC: 2017 Oct 4.
Published in final edited form as: Nat Rev Mol Cell Biol. 2016 Aug 24;17(11):691–702. doi: 10.1038/nrm.2016.96

Fig. 4. Crosstalk between brown/beige adipocytes and other adipose-resident cells.

Fig. 4

(a) Adipocytes and nerve cells. Parenchymal sympathetic nerve fibers secrete catecholamines to regulate the development and the thermogenic function of brown/beige adipocytes. Conversely, brown/beige adipocytes might also promote nerve remodeling by producing neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neuregulin 4 (NRG4).

(b) Brown/beige adipocytes and vasculature. Adipocytes secrete vascular endothelial growth factor (VEGF) to stimulate angiogenesis. The enhanced vasculature provides increased nutrition and oxygen to sustain thermogenesis in brown/beige adipocytes, thereby promoting energy expenditure and insulin sensitivity.

(c) Brown/beige adipocytes and immune cells. Interleukin (IL)-33 activates group 2 innate lymphoid cells (ILC2s), which secrete IL-13 and IL-5. IL-5 activates eosinophils, which produce IL-4. IL-4, in turn, induces the differentiation of M2 macrophages, which provide a critical source of catecholamines for beige fat activation. IL-4 (from eosinophils or ILC2s) also acts directly on Pdgfrα+ precursors to increase their proliferation and differentiation into beige adipocytes. Furthermore, ILC2s secrete met-enkephalin peptides to promote beige adipocyte differentiation. METRNL (Meteorin-like), secreted by muscle and adipose, activates eosinophils and type II cytokine signaling to drive beige adipocyte development.