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Addressing the mechanisms of white adipose tissue (WAT) browning in CAC, we now show that cachexigenic tumors activate type 2 immunity in cachectic WAT, generating a neuroprotective environment that increases peripheral sympathetic activity. Increased sympathetic activation, in turn, results in increased neuronal catecholamine synthesis and secretion, \u03b2-adrenergic activation of adipocytes, and induction of WAT browning. Two genetic mouse models validated this progression of events. 1) Interleukin-4 receptor deficiency impeded the alternative activation of macrophages, reduced sympathetic activity, and restrained WAT browning, and 2) reduced catecholamine synthesis in peripheral dopamine \u03b2-hydroxylase (DBH)\u2013deficient mice prevented cancer-induced WAT browning and adipose atrophy. Targeting the intraadipose macrophage-sympathetic neuron cross-talk represents a promising therapeutic approach to ameliorate cachexia in cancer patients.<\/jats:p>","DOI":"10.1073\/pnas.2112840119","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T16:10:37Z","timestamp":1645719037000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":81,"title":["An immune-sympathetic neuron communication axis guides adipose tissue browning in cancer-associated cachexia"],"prefix":"10.1073","volume":"119","author":[{"given":"Hao","family":"Xie","sequence":"first","affiliation":[{"name":"Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Heier","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, University of Graz, 8010 Graz, 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