Editors' ChoiceMetabolism

Fat expansion through norepinephrine catabolism

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Sci. Signal.  14 Nov 2017:
Vol. 10, Issue 505, eaar4569
DOI: 10.1126/scisignal.aar4569

Certain macrophage populations limit norepinephrine-induced lipolysis in adipose tissues in response to aging or obesity.

Fasting or cold exposure triggers the release of the catecholamine norepinephrine from sympathetic neurons that innervate adipose tissues. Norepinephrine promotes the lipolysis of triglycerides, a process that reduces white adipose tissue mass and overall adiposity and enables brown adipose tissue to produce heat. Fasting-induced lipolysis is impaired in adipose tissue in the elderly, which Camell et al. (see also Czech) found was due to the degradation of norepinephrine by adipose tissue macrophages (ATMs). Aging increased the expression of genes encoding norepinephrine-degrading enzymes, such as monoamine oxidase A (MAOA), in ATMs, an effect that depended on the NLRP3 inflammasome and GDF-3 (growth differentiation factor 3), a transforming growth factor–family member. Treating aged mice with an MAOA inhibitor increased adipose tissue concentrations of norepinephrine and rescued fasting-induced lipolysis. In another paper, Pirzgalska et al. characterized a population of macrophages associated with sympathetic neurons that were distinct from ATMs (and that was also identified by Camell et al.). These macrophages, which the authors called SAMs (sympathetic neuron–associated macrophages), took up norepinephrine through the transporter SLC6A2 and catabolized it through MAOA. Diet- or genetically induced obesity in mice increased the number of SAMs, which expressed genes encoding proinflammatory cytokines at sympathetic fibers. Of the cells in the hematopoietic lineage, Slc6a2 expression was specific to SAMs, and ob/ob mice that received Slc6a2–/– bone marrow cells had increased circulating concentrations of norepinephrine and weighed less than did ob/ob mice that received control bone marrow cells. Immunohistochemistry analysis showed the presence of macrophages that were positive for SLC6A2 and MAOA in human sympathetic ganglia. Thus, certain macrophage populations limit lipolysis in adipose tissue in response to aging or obesity by acting as a sink for norepinephrine.

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