LAUSR

© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Nature reviews | Endocrinology Original article Jun, H. et al. An immune–beige adipocyte communication via nicotinic acetylcholine receptor signaling. Nat. Med. https://doi.org/10.1038/ s41591-018-0032-8 (2018) Beige fat cells are a potential therapeutic target for the prevention and treatment of human obesity, but little is known about the mechanisms underlying beige fat activation. Now, Jun wu and colleagues have moved us one step closer towards this goal by showing that the α2 subunit of the nicotinic acetylcholine receptor (CHrNa2) is upregulated in beige fat cells following their activation. “the therapeutic potential of beige fat cells is clear: genetic manipulations that create more beige fat in mice have strong antiobesity and antidiabetic effects and cumulative evidence supports a protective role of activated thermogenic fat in maintaining systemic metabolic homeostasis in humans,” explains wu. “in our study we used a calciumimaging assay in combination with Ucp1–Cre–rFP primary inguinal fat cell culture and flow cytometric analysis using Chat–GFP reporter mice to investigate the molecular mechanisms and signalling networks that regulate beige fat development and activation.” the authors found that the expression of CHrNa2 is upregulated in activated beige fat cells from subcutaneous adipose depots. they demonstrated that that a subgroup of acetylcholineproducing CD45+ haematopoietic lineage cells within these depots mediate CHrNa2 signalling in beige adipocytes. wu and colleagues then went on to investigate how this immune cell–beige adipocyte communication process is regulated during cold exposure and obesity. “we found that Chrna2-knockout mice (in which the canonical βadrenergic regulation of the beige fat remains intact) demonstrate a compromised adaptation to cold and exacerbated dietinduced obesity,” adds wu. “these results not only further confirm the physiological significance of beige adipocytes as an important metabolic regulator, but also highlight the essential role of catecholamineindependent, acetylcholine–CHrNa2 signalling in energy metabolism.” wu and colleagues now want to investigate whether any of the acetylcholineproducing CD45+ cells within the subcutaneous fat tissue have a dominant role in regulating the activation of beige adipocytes that is mediated by CHrNa2. “the identification of such a subset would help to incorporate the acetylcholine–beige fat signalling pathway into the already identified signalling network between immune cells and adipocytes and place this newly defined pathway within the interconnected metabolic matrix,” concludes wu. Alan Morris C re di t: S te ve G sc hm ei ss ne r/ Sc ie nc e Ph ot o Li br ar y