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This concept is well studied in the context of high fat diet induced obesity (HFDO), yet has not been investigated in the context of cachexia, a devastating metabolic syndrome characterized by anorexia, fatigue, and muscle catabolism. We show that microglia accumulate specifically in the MBH early in pancreatic ductal adenocarcinoma (PDAC)\u2010associated cachexia and assume an activated morphology. Furthermore, we observe astrogliosis in the MBH and hippocampus concurrent with cachexia initiation. We next show that circulating immune cells resembling macrophages infiltrate the MBH. PDAC\u2010derived factors induced microglia to express a transcriptional profile in vitro that was distinct from that induced by lipopolysaccharide (LPS). Microglia depletion through CSF1\u2010R antagonism resulted in accelerated cachexia onset and increased anorexia, fatigue, and muscle catabolism during PDAC. This corresponded with increased hypothalamic\u2013pituitary\u2013adrenal (HPA) axis activation. CSF1\u2010R antagonism had little effect on inflammatory response in the circulation, liver, or tumor. These findings demonstrate that microglia are protective against PDAC cachexia and provide mechanistic insight into this function.<\/jats:p>","DOI":"10.1002\/glia.23796","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T12:58:10Z","timestamp":1581339490000},"page":"1479-1494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Microglia in the hypothalamus respond to tumor\u2010derived factors and are protective against cachexia during pancreatic cancer"],"prefix":"10.1002","volume":"68","author":[{"given":"Kevin G.","family":"Burfeind","sequence":"first","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"},{"name":"Medical Scientist Training Program, Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason A.","family":"Norgard","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Levasseur","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Huisman","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"},{"name":"Medical Scientist Training Program, Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennan","family":"Olson","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"},{"name":"Medical Scientist Training Program, Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2675-7047","authenticated-orcid":false,"given":"Daniel L.","family":"Marks","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland Oregon"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University  Portland Oregon"},{"name":"Brenden\u2010Colson Center for Pancreatic Care Oregon Health and &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-008-0505-z"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1595-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00032"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00015-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111020"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.10.038"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.05.021"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205858109"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0764"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130875"},{"issue":"1","key":"e_1_2_7_13_1","first-page":"H342","article-title":"Arginase modulates nitric oxide production in activated macrophages","volume":"274","author":"Chang C. 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