{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:31:41Z","timestamp":1790865101811,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201806820029"],"award-info":[{"award-number":["201806820029"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rectus abdominis muscle biopsies were collected during surgery of patients with pancreatic ductal adenocarcinoma (<jats:italic>n<\/jats:italic>\u00a0=\u00a010 without cachexia, <jats:italic>n<\/jats:italic>\u00a0=\u00a020 cachectic without inflammation (CRP\u00a0&lt;\u00a010\u00a0mg\/L), <jats:italic>n<\/jats:italic>\u00a0=\u00a010 cachectic with inflammation (CRP\u00a0\u2265\u00a010\u00a0mg\/L). L3\u2010CT scans were analysed to assess body composition based on validated thresholds in Hounsfield units (HU). Muscle sections were stained with Oil\u2010Red O and H&amp;E to assess general lipid accumulation and atrophy. Untargeted lipidomic analyses were performed on laser\u2010microdissected myotubes using LC\u2013MS\/MS. The spatial distribution of intramyocellular lipids with differential abundance between groups was visualized by mass\u2010spectrometry imaging. Genes coding for inflammation markers and enzymes involved in <jats:italic>de novo<\/jats:italic> ceramide synthesis were studied by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Muscle radiation attenuation was lower in cachectic patients with inflammation (median 24.3 [18.6\u201330.8] HU) as compared with those without inflammation (34.2 [29.3\u201338.7] HU, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.033) or no cachexia (37.4 [33.9\u201342.9] HU, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012). Accordingly, intramyocellular lipid content was lower in non\u2010cachectic patients (1.9 [1.6\u20132.1]%) as compared with those with cachexia with inflammation (5.5 [4.5\u20137.3]%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) or without inflammation (4.8 [2.6\u20136.0]%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.017). Intramyocellular lipid accumulation was associated with both local IL\u20106 mRNA levels (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a00.57, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.015) and systemic CRP levels (<jats:italic>r<\/jats:italic><jats:sub><jats:italic>s<\/jats:italic><\/jats:sub>\u00a0=\u00a00.49, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.024). Compared with non\u2010cachectic subjects, cachectic patients had a higher relative abundance of intramyocellular glycerophospholipids and a lower relative abundance of glycerolipids. Furthermore, increases in several intramyocellular lipids such as SM(d36:1), PC(34:1), and TG(48:1) were found in cachectic patients with inflammation and correlated with specific cachexia features. Altered intramyocellular lipid species such as PC(34:1), LPC(18:2), and TG(48:1) showed an uneven distribution in muscle sections of cachectic and non\u2010cachectic patients, with areas featuring abundance of these lipids next to areas almost devoid of them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Intramyocellular lipid accumulation in patients with cachexia is associated with both local and systemic inflammation, and characterized by changes in defined lipid species such as glycerolipids and glycerophospholipids.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13474","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T04:39:28Z","timestamp":1715315968000},"page":"1283-1297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inflammation\u2010associated intramyocellular lipid alterations in human pancreatic cancer cachexia"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9337-3935","authenticated-orcid":false,"given":"Min","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Imaging Mass Spectrometry, Maastricht Multimodal Molecular Imaging (M4i) Institute Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"van der Kroft","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of General, Visceral and Transplantation Surgery RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.J.","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel R.","family":"Aberle","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Grgic","sequence":"additional","affiliation":[{"name":"Division of Imaging Mass Spectrometry, Maastricht Multimodal Molecular Imaging (M4i) Institute Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf P.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of General, Visceral and Transplantation Surgery RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Wiltberger","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Balluff","sequence":"additional","affiliation":[{"name":"Division of Imaging Mass Spectrometry, Maastricht Multimodal Molecular Imaging (M4i) Institute Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G.","family":"Schaap","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of General, Visceral and Transplantation Surgery RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron M.A.","family":"Heeren","sequence":"additional","affiliation":[{"name":"Division of Imaging Mass Spectrometry, Maastricht Multimodal Molecular Imaging (M4i) Institute Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.M.","family":"Olde Damink","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University  Maastricht The Netherlands"},{"name":"Department of General, Visceral and Transplantation Surgery RWTH University 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