Unusual macrophages contribute to obesity

Immunometabolism The role of macrophages in the regulation of norepinephrine (NE)–mediated thermogenesis has been a topic of much recent debate. Pirzgalska et al. report a specialized subset of CX3CR1+ sympathetic nerve–associated macrophages (SAMs) in adipose tissue. SAMs display dynamic dendritiform processes but are closer to macrophages than microglia in their gene expression profile. However, SAMs uniquely possess the machinery for NE transport (SLC6A2) and degradation (MAOA) and are recruited and activated in mouse models of obesity. The lineage-specific deletion of Slc6a2 in SAMs results in increased NE levels, thermogenesis, browning of white fat, and weight loss. Given that human sympathetic ganglia are also infiltrated with NE-degrading SAMs, this work suggests an intriguing new target for managing the global obesity epidemic. Nat. Med. 10.1038/nm.4422 (2017).