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Systemic inflammation is considered to be a key driver of cancer cachexia; however, clinical studies with anti\u2010inflammatory drugs failed to show distinct cachexia\u2010inhibiting effects. To address this contradiction, we investigated the functional importance of innate immune cells for hepatocellular carcinoma (HCC)\u2010associated cachexia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A transgenic HCC mouse model was intercrossed with mice harbouring a defect in myeloid cell\u2010mediated inflammation. Body composition of mice was analysed via nuclear magnetic resonance spectroscopy and microcomputed tomography. Quantitative PCR was used to determine adipose tissue browning and polarization of adipose tissue macrophages. The activation state of distinct areas of the hypothalamus was analysed via immunofluorescence. Multispectral immunofluorescence imaging and immunoblot were applied to characterize sympathetic neurons and macrophages in visceral adipose tissue. Quantification of pro\u2010inflammatory cytokines in mouse serum was performed with a multiplex immunoassay. Visceral adipose tissue of HCC patients was quantified via the L3 index of computed tomography scans obtained during routine clinical care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified robust cachexia in the HCC mouse model as evidenced by a marked loss of visceral fat and lean mass. Computed tomography\u2010based analyses demonstrated that a subgroup of human HCC patients displays reduced visceral fat mass, complementing the murine data. While the myeloid cell\u2010mediated inflammation defect resulted in reduced expression of pro\u2010inflammatory cytokines in the serum of HCC\u2010bearing mice, this unexpectedly did not translate into diminished but rather enhanced cachexia\u2010associated fat loss. Defective myeloid cell\u2010mediated inflammation was associated with decreased macrophage abundance in visceral adipose tissue, suggesting a role for local macrophages in the regulation of cancer\u2010induced fat loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Myeloid cell\u2010mediated inflammation displays a rather unexpected beneficial function in a murine HCC model. These results demonstrate that immune cells are capable of protecting the host against cancer\u2010induced tissue wasting, adding a further layer of complexity to the pathogenesis of cachexia and providing a potential explanation for the contradictory results of clinical studies with anti\u2010inflammatory drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12450","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T06:06:22Z","timestamp":1563429982000},"page":"1128-1142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Macrophages protect against loss of adipose tissue during cancer cachexia"],"prefix":"10.1002","volume":"10","author":[{"given":"Merve","family":"Erdem","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery University Hospital RWTH Aachen  Aachen Germany"},{"name":"Berlin School of Integrative 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