{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:40:36Z","timestamp":1792431636470,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["F30CA254033"],"award-info":[{"award-number":["F30CA254033"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA217989"],"award-info":[{"award-number":["R01CA217989"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["K08CA245188"],"award-info":[{"award-number":["K08CA245188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, a devastating clinical entity characterized by decreased nutrition and progressive wasting. We demonstrate that LCN2 is robustly upregulated in murine models of pancreatic cancer, its expression is associated with reduced food consumption, and <jats:italic>Lcn2<\/jats:italic> deletion is protective from cachexia-anorexia. Consistent with LCN2\u2019s proposed MC4R-dependent role in cancer-induced anorexia, pharmacologic MC4R antagonism mitigates cachexia-anorexia, while restoration of <jats:italic>Lcn2<\/jats:italic> expression in the bone marrow is sufficient in restoring the anorexia feature of cachexia. Finally, we observe that LCN2 levels correlate with fat and lean mass wasting and is associated with increased mortality in patients with pancreatic cancer. Taken together, these findings implicate LCN2 as a pathologic mediator of appetite suppression during pancreatic cancer cachexia.<\/jats:p>","DOI":"10.1038\/s41467-021-22361-3","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T10:02:48Z","timestamp":1617703368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Lipocalin 2 mediates appetite suppression during pancreatic cancer cachexia"],"prefix":"10.1038","volume":"12","author":[{"given":"Brennan","family":"Olson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxia","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason A.","family":"Norgard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Levasseur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Buenafe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin G.","family":"Burfeind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3225-3649","authenticated-orcid":false,"given":"Katherine A.","family":"Michaelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine R.","family":"Pelz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Mendez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-3854","authenticated-orcid":false,"given":"Jared","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0507-4669","authenticated-orcid":false,"given":"Stephanie M.","family":"Krasnow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-4948","authenticated-orcid":false,"given":"Aaron J.","family":"Grossberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2675-7047","authenticated-orcid":false,"given":"Daniel L.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"22361_CR1","doi-asserted-by":"publisher","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","volume":"4","author":"VE Baracos","year":"2018","unstructured":"Baracos, V. E., Martin, L., Korc, M., Guttridge, D. C. & Fearon, K. C. H. Cancer-associated cachexia. Nat. Rev. Dis. Prim. 4, 17105 (2018).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"22361_CR2","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","volume":"12","author":"K Fearon","year":"2011","unstructured":"Fearon, K. et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 12, 489\u2013495 (2011).","journal-title":"Lancet Oncol."},{"key":"22361_CR3","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/ncpneph0273","volume":"2","author":"RH Mak","year":"2006","unstructured":"Mak, R. H., Cheung, W., Cone, R. D. & Marks, D. L. Mechanisms of disease: cytokine and adipokine signaling in uremic cachexia. Nat. Clin. Pract. Nephrol. 2, 527\u2013534 (2006).","journal-title":"Nat. Clin. Pract. Nephrol."},{"key":"22361_CR4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s13539-014-0164-8","volume":"5","author":"S von Haehling","year":"2014","unstructured":"von Haehling, S. & Anker, S. D. Prevalence, incidence and clinical impact of cachexia: facts and numbers-update 2014. J. Cachexia Sarcopenia Muscle 5, 261\u2013263 (2014).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"22361_CR5","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s11605-008-0505-z","volume":"12","author":"J Bachmann","year":"2008","unstructured":"Bachmann, J. et al. Cachexia worsens prognosis in patients with resectable pancreatic cancer. J. Gastrointest. Surg.: Off. J. Soc. Surg. Alimentary Trac. 12, 1193\u20131201 (2008).","journal-title":"J. Gastrointest. Surg.: Off. J. Soc. Surg. Alimentary Trac."},{"key":"22361_CR6","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.cmet.2016.10.010","volume":"24","author":"TR Flint","year":"2016","unstructured":"Flint, T. R. et al. Tumor-induced IL-6 reprograms host metabolism to suppress anti-tumor immunity. Cell Metab. 24, 672\u2013684 (2016).","journal-title":"Cell Metab."},{"key":"22361_CR7","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/s41586-018-0235-7","volume":"558","author":"LV Danai","year":"2018","unstructured":"Danai, L. V. et al. Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature 558, 600\u2013604 (2018).","journal-title":"Nature"},{"key":"22361_CR8","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1002\/cncr.31128","volume":"124","author":"N Katakami","year":"2018","unstructured":"Katakami, N. et al. Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer 124, 606\u2013616 (2018).","journal-title":"Cancer"},{"key":"22361_CR9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.lungcan.2017.07.023","volume":"112","author":"K Nishie","year":"2017","unstructured":"Nishie, K., Yamamoto, S., Nagata, C., Koizumi, T. & Hanaoka, M. Anamorelin for advanced non-small-cell lung cancer with cachexia: systematic review and meta-analysis. Lung Cancer 112, 25\u201334 (2017).","journal-title":"Lung Cancer"},{"key":"22361_CR10","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.2217\/fon-2017-0141","volume":"13","author":"DC Currow","year":"2017","unstructured":"Currow, D. C. & Skipworth, R. J. The emerging role of anamorelin hydrochloride in the management of patients with cancer anorexia-cachexia. Future Oncol. 13, 1767\u20131783 (2017).","journal-title":"Future Oncol."},{"key":"22361_CR11","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.tem.2017.01.003","volume":"28","author":"AR Moschen","year":"2017","unstructured":"Moschen, A. R., Adolph, T. E., Gerner, R. R., Wieser, V. & Tilg, H. Lipocalin-2: a master mediator of Intestinal and metabolic Inflammation. Trends Endocrinol. Metab. 28, 388\u2013397 (2017).","journal-title":"Trends Endocrinol. Metab."},{"key":"22361_CR12","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1158\/0008-5472.CAN-16-1986","volume":"77","author":"SB Gomez-Chou","year":"2017","unstructured":"Gomez-Chou, S. B. et al. Lipocalin-2 promotes pancreatic ductal adenocarcinoma by regulating inflammation in the tumor microenvironment. Cancer Res. 77, 2647\u20132660 (2017).","journal-title":"Cancer Res."},{"key":"22361_CR13","doi-asserted-by":"publisher","first-page":"4065","DOI":"10.1172\/JCI42004","volume":"120","author":"A Viau","year":"2010","unstructured":"Viau, A. et al. Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J. Clin. Investig. 120, 4065\u20134076 (2010).","journal-title":"J. Clin. Investig."},{"key":"22361_CR14","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1093\/eurheartj\/ehp088","volume":"30","author":"A Yndestad","year":"2009","unstructured":"Yndestad, A. et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur. Heart J. 30, 1229\u20131236 (2009).","journal-title":"Eur. Heart J."},{"key":"22361_CR15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nature21697","volume":"543","author":"I Mosialou","year":"2017","unstructured":"Mosialou, I. et al. MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature 543, 385\u2013390 (2017).","journal-title":"Nature"},{"key":"22361_CR16","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/nn1455","volume":"8","author":"RD Cone","year":"2005","unstructured":"Cone, R. D. Anatomy and regulation of the central melanocortin system. Nat. Neurosci. 8, 571\u2013578 (2005).","journal-title":"Nat. Neurosci."},{"key":"22361_CR17","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1002\/jcsm.12225","volume":"8","author":"KA Michaelis","year":"2017","unstructured":"Michaelis, K. A. et al. Establishment and characterization of a novel murine model of pancreatic cancer cachexia. J. Cachexia Sarcopenia Muscle 8, 824\u2013838 (2017).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"22361_CR18","doi-asserted-by":"publisher","first-page":"5960","DOI":"10.1074\/jbc.M113.532234","volume":"289","author":"P Zhao","year":"2014","unstructured":"Zhao, P., Elks, C. M. & Stephens, J. M. The induction of lipocalin-2 protein expression in vivo and in vitro. J. Biol. Chem. 289, 5960\u20135969 (2014).","journal-title":"J. Biol. Chem."},{"key":"22361_CR19","doi-asserted-by":"publisher","first-page":"e96997","DOI":"10.1371\/journal.pone.0096997","volume":"9","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. Lipocalin 2 expression and secretion is highly regulated by metabolic stress, cytokines, and nutrients in adipocytes. PLoS ONE 9, e96997 (2014).","journal-title":"PLoS ONE"},{"key":"22361_CR20","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/hep.27447","volume":"61","author":"MJ Xu","year":"2015","unstructured":"Xu, M. J. et al. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6\/STAT3. Hepatology 61, 692\u2013702 (2015).","journal-title":"Hepatology"},{"key":"22361_CR21","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/jcsm.12377","volume":"10","author":"X Zhu","year":"2019","unstructured":"Zhu, X. et al. MyD88 signalling is critical in the development of pancreatic cancer cachexia. J. Cachexia Sarcopenia Muscle 10, 378\u2013390 (2019).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"22361_CR22","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1182\/blood.V83.3.799.799","volume":"83","author":"L Kjeldsen","year":"1994","unstructured":"Kjeldsen, L., Bainton, D. F., Sengelov, H. & Borregaard, N. Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood 83, 799\u2013807 (1994).","journal-title":"Blood"},{"key":"22361_CR23","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41590-019-0397-y","volume":"20","author":"H Baazim","year":"2019","unstructured":"Baazim, H. et al. CD8(+) T cells induce cachexia during chronic viral infection. Nat. Immunol. 20, 701\u2013710 (2019).","journal-title":"Nat. Immunol."},{"key":"22361_CR24","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1139\/H08-075","volume":"33","author":"M Mourtzakis","year":"2008","unstructured":"Mourtzakis, M. et al. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl. Physiol. Nutr. Metab. 33, 997\u20131006 (2008).","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"22361_CR25","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cmpb.2019.05.023","volume":"177","author":"M Ogluszka","year":"2019","unstructured":"Ogluszka, M., Orzechowska, M., Jedroszka, D., Witas, P. & Bednarek, A. K. Evaluate cutpoints: adaptable continuous data distribution system for determining survival in Kaplan\u2013Meier estimator. Comput Methods Prog. Biomed. 177, 133\u2013139 (2019).","journal-title":"Comput Methods Prog. Biomed."},{"key":"22361_CR26","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nature03104","volume":"432","author":"TH Flo","year":"2004","unstructured":"Flo, T. H. et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917\u2013921 (2004).","journal-title":"Nature"},{"key":"22361_CR27","doi-asserted-by":"publisher","unstructured":"Burfeind, K. G. et al. Microglia in the hypothalamus respond to tumor-derived factors and are protective against cachexia during pancreatic cancer. Glia, https:\/\/doi.org\/10.1002\/glia.23796 (2020).","DOI":"10.1002\/glia.23796"},{"key":"22361_CR28","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.3748\/wjg.v20.i7.1807","volume":"20","author":"SM Alwahsh","year":"2014","unstructured":"Alwahsh, S. M. et al. Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty liver. World J. Gastroenterol. 20, 1807\u20131821 (2014).","journal-title":"World J. Gastroenterol."},{"key":"22361_CR29","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1126\/science.1065874","volume":"294","author":"SC Bodine","year":"2001","unstructured":"Bodine, S. C. et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294, 1704\u20131708 (2001).","journal-title":"Science"},{"key":"22361_CR30","doi-asserted-by":"publisher","first-page":"14440","DOI":"10.1073\/pnas.251541198","volume":"98","author":"MD Gomes","year":"2001","unstructured":"Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A. & Goldberg, A. L. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc. Natl Acad. Sci. U. S. A. 98, 14440\u201314445 (2001).","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"22361_CR31","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/S1097-2765(04)00211-4","volume":"14","author":"TN Stitt","year":"2004","unstructured":"Stitt, T. N. et al. The IGF-1\/PI3K\/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell 14, 395\u2013403 (2004).","journal-title":"Mol. Cell"},{"key":"22361_CR32","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/S0092-8674(04)00400-3","volume":"117","author":"M Sandri","year":"2004","unstructured":"Sandri, M. et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117, 399\u2013412 (2004).","journal-title":"Cell"},{"key":"22361_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7670","volume":"6","author":"G Milan","year":"2015","unstructured":"Milan, G. et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat. Commun. 6, 6670 (2015).","journal-title":"Nat. Commun."},{"key":"22361_CR34","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1007\/s00213-019-05190-7","volume":"236","author":"EG Vichaya","year":"2019","unstructured":"Vichaya, E. G. et al. Lipocalin-2 is dispensable in inflammation-induced sickness and depression-like behavior. Psychopharmacology 236, 2975\u20132982 (2019).","journal-title":"Psychopharmacology"},{"key":"22361_CR35","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/mp.2016.243","volume":"23","author":"SS Kang","year":"2018","unstructured":"Kang, S. S. et al. Lipocalin-2 protects the brain during inflammatory conditions. Mol. Psychiatry 23, 344\u2013350 (2018).","journal-title":"Mol. Psychiatry"},{"key":"22361_CR36","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.bbadis.2013.01.014","volume":"1832","author":"E Borkham-Kamphorst","year":"2013","unstructured":"Borkham-Kamphorst, E. et al. Protective effects of lipocalin-2 (LCN2) in acute liver injury suggest a novel function in liver homeostasis. Biochim Biophys. Acta 1832, 660\u2013673 (2013).","journal-title":"Biochim Biophys. Acta"},{"key":"22361_CR37","doi-asserted-by":"publisher","first-page":"e67693","DOI":"10.1371\/journal.pone.0067693","volume":"8","author":"K Eller","year":"2013","unstructured":"Eller, K. et al. Lipocalin-2 expressed in innate immune cells is an endogenous inhibitor of inflammation in murine nephrotoxic serum nephritis. PLoS ONE 8, e67693 (2013).","journal-title":"PLoS ONE"},{"key":"22361_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12973","volume":"7","author":"J Barasch","year":"2016","unstructured":"Barasch, J. et al. Disposal of iron by a mutant form of lipocalin 2. Nat. Commun. 7, 12973 (2016).","journal-title":"Nat. Commun."},{"key":"22361_CR39","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1073\/pnas.1720570115","volume":"115","author":"E Song","year":"2018","unstructured":"Song, E. et al. Holo-lipocalin-2-derived siderophores increase mitochondrial ROS and impair oxidative phosphorylation in rat cardiomyocytes. Proc. Natl Acad. Sci. U. S. A. 115, 1576\u20131581 (2018).","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"22361_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15825-4","volume":"7","author":"A Ishii","year":"2017","unstructured":"Ishii, A. et al. Obesity-promoting and anti-thermogenic effects of neutrophil gelatinase-associated lipocalin in mice. Sci. Rep. 7, 15501 (2017).","journal-title":"Sci. Rep."},{"key":"22361_CR41","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.2337\/db09-1735","volume":"59","author":"H Guo","year":"2010","unstructured":"Guo, H. et al. Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice. Diabetes 59, 1376\u20131385 (2010).","journal-title":"Diabetes"},{"key":"22361_CR42","doi-asserted-by":"publisher","first-page":"872","DOI":"10.2337\/db09-1541","volume":"59","author":"IK Law","year":"2010","unstructured":"Law, I. K. et al. Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes 59, 872\u2013882 (2010).","journal-title":"Diabetes"},{"key":"22361_CR43","doi-asserted-by":"publisher","first-page":"E825","DOI":"10.1152\/ajpendo.00147.2011","volume":"301","author":"LS Jun","year":"2011","unstructured":"Jun, L. S., Siddall, C. P. & Rosen, E. D. A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance. Am. J. Physiol. Endocrinol. Metab. 301, E825\u2013E835 (2011).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"22361_CR44","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.cmet.2012.04.019","volume":"15","author":"M Hatori","year":"2012","unstructured":"Hatori, M. et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 15, 848\u2013860 (2012).","journal-title":"Cell Metab."},{"key":"22361_CR45","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.cmet.2014.11.001","volume":"20","author":"A Chaix","year":"2014","unstructured":"Chaix, A., Zarrinpar, A., Miu, P. & Panda, S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 20, 991\u20131005 (2014).","journal-title":"Cell Metab."},{"key":"22361_CR46","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.cmet.2015.05.012","volume":"22","author":"S Brandhorst","year":"2015","unstructured":"Brandhorst, S. et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 22, 86\u201399 (2015).","journal-title":"Cell Metab."},{"key":"22361_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/srep11026","volume":"5","author":"H Cheng","year":"2015","unstructured":"Cheng, H. et al. Prognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: a meta-analysis. Sci. Rep. 5, 11026 (2015).","journal-title":"Sci. Rep."},{"key":"22361_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00859-5","volume":"7","author":"Y Chen","year":"2017","unstructured":"Chen, Y., Yan, H., Wang, Y., Shi, Y. & Dai, G. Significance of baseline and change in neutrophil-to-lymphocyte ratio in predicting prognosis: a retrospective analysis in advanced pancreatic ductal adenocarcinoma. Sci. Rep. 7, 753 (2017).","journal-title":"Sci. Rep."},{"key":"22361_CR49","doi-asserted-by":"publisher","unstructured":"Prado, C. M., Purcell, S. A. & Laviano, A. Nutrition interventions to treat low muscle mass in cancer. J. Cachexia Sarcopenia Muscle, https:\/\/doi.org\/10.1002\/jcsm.12525 (2020).","DOI":"10.1002\/jcsm.12525"},{"key":"22361_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75745-8","volume":"10","author":"N Iwai","year":"2020","unstructured":"Iwai, N. et al. Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer. Sci. Rep. 10, 18758 (2020).","journal-title":"Sci. Rep."},{"key":"22361_CR51","doi-asserted-by":"publisher","first-page":"197","DOI":"10.14701\/ahbps.2018.22.3.197","volume":"22","author":"A Giakoustidis","year":"2018","unstructured":"Giakoustidis, A. et al. Identifying the role of neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio as prognostic markers in patients undergoing resection of pancreatic ductal adenocarcinoma. Ann. Hepatobiliary Pancreat. Surg. 22, 197\u2013207 (2018).","journal-title":"Ann. Hepatobiliary Pancreat. Surg."},{"key":"22361_CR52","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nature14282","volume":"522","author":"SB Coffelt","year":"2015","unstructured":"Coffelt, S. B. et al. IL-17-producing \u03b3\u03b4 T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522, 345\u2013348 (2015).","journal-title":"Nature"},{"key":"22361_CR53","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S1470-2045(08)70153-0","volume":"9","author":"CM Prado","year":"2008","unstructured":"Prado, C. M. et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 9, 629\u2013635 (2008).","journal-title":"Lancet Oncol."},{"key":"22361_CR54","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1038\/mt.2013.36","volume":"21","author":"TJ Hofmann","year":"2013","unstructured":"Hofmann, T. J. et al. Transplanted murine long-term repopulating hematopoietic cells can differentiate to osteoblasts in the marrow stem cell niche. Mol. Ther.: J. Am. Soc. Gene Ther. 21, 1224\u20131231 (2013).","journal-title":"Mol. Ther.: J. Am. Soc. Gene Ther."},{"key":"22361_CR55","doi-asserted-by":"publisher","first-page":"11761","DOI":"10.1073\/pnas.0404626101","volume":"101","author":"M Dominici","year":"2004","unstructured":"Dominici, M. et al. Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation. Proc. Natl Acad. Sci. U. S. A. 101, 11761\u201311766 (2004).","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"22361_CR56","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1136\/hrt.24.3.257","volume":"24","author":"AM Katz","year":"1962","unstructured":"Katz, A. M. & Katz, P. B. Diseases of the heart in the works of Hippocrates. Br. Heart J. 24, 257\u2013264 (1962).","journal-title":"Br. Heart J."},{"key":"22361_CR57","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.bbi.2018.05.021","volume":"73","author":"KG Burfeind","year":"2018","unstructured":"Burfeind, K. G. et al. TRIF is a key inflammatory mediator of acute sickness behavior and cancer cachexia. Brain Behav. Immun. 73, 364\u2013374 (2018).","journal-title":"Brain Behav. Immun."},{"key":"22361_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12657-w","volume":"10","author":"KA Michaelis","year":"2019","unstructured":"Michaelis, K. A. et al. The TLR7\/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer. Nat. Commun. 10, 4682 (2019).","journal-title":"Nat. Commun."},{"key":"22361_CR59","doi-asserted-by":"crossref","first-page":"e1375","DOI":"10.21769\/BioProtoc.1375","volume":"5","author":"D Kraus","year":"2015","unstructured":"Kraus, D., Yang, Q. & Kahn, B. B. Lipid extraction from mouse feces. Bio Protoc. 5, e1375 (2015).","journal-title":"Bio Protoc."},{"key":"22361_CR60","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1109\/TMI.2015.2479252","volume":"35","author":"K Popuri","year":"2016","unstructured":"Popuri, K., Cobzas, D., Esfandiari, N., Baracos, V. & Jagersand, M. Body composition assessment in axial CT images using FEM-based automatic segmentation of skeletal muscle. IEEE Trans. Med. Imaging 35, 512\u2013520 (2016).","journal-title":"IEEE Trans. Med. Imaging"},{"key":"22361_CR61","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/SPC.0b013e328331124a","volume":"3","author":"CM Prado","year":"2009","unstructured":"Prado, C. M., Birdsell, L. A. & Baracos, V. E. The emerging role of computerized tomography in assessing cancer cachexia. Curr. Opin. Support. Palliat. Care 3, 269\u2013275 (2009).","journal-title":"Curr. Opin. Support. Palliat. Care"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22361-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22361-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22361-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T11:52:46Z","timestamp":1669981966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22361-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["22361"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-22361-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]},"assertion":[{"value":"15 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"D.L.M. is a consultant for Pfizer, Inc. and Alkermes, Inc. D.L.M. is a consultant, has received grant funding, and has equity in Tensive Controls, Inc. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2057"}}