{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:46:08Z","timestamp":1784252768987,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011878","name":"Vlaamse regering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011878","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":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Muscle weakness is a frequently occurring complication of sepsis, associated with increased morbidity and mortality. Interestingly, obesity attenuates sepsis\u2010induced muscle wasting and weakness. As the adipokine leptin is strongly elevated in obesity and has been shown to affect muscle homeostasis in non\u2010septic conditions, we aimed to investigate whether leptin mediates the protective effect of obesity on sepsis\u2010induced muscle weakness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a mouse model of sepsis, we investigated the effects of genetic leptin inactivation in obese mice (leptin\u2010deficient obese mice vs. diet\u2010induced obese mice) and of leptin supplementation in lean mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a0110). We assessed impact on survival, body weight and composition, markers of muscle wasting and weakness, inflammation, and lipid metabolism. In human lean and overweight\/obese intensive care unit (ICU) patients, we assessed markers of protein catabolism (<jats:italic>n<\/jats:italic>\u00a0=\u00a01388) and serum leptin (<jats:italic>n<\/jats:italic>\u00a0=\u00a0150).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sepsis mortality was highest in leptin\u2010deficient obese mice (53% vs. 23% in diet\u2010induced obese mice and 37% in lean mice, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). Irrespective of leptin, after 5\u00a0days of sepsis, lean mice lost double the amount of lean body mass than obese mice (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0005). Also, irrespective of leptin, obese mice maintained specific muscle force up to healthy levels (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.3) whereas lean mice suffered from reduced specific muscle force (72% of healthy controls, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0002). As compared with lean septic mice, both obese septic groups had less muscle atrophy, liver amino acid catabolism, and inflammation with a 50% lower plasma TNF\u03b1 increase (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005). Conversely, again mainly irrespective of leptin, obese mice lost double amount of fat mass than lean mice after 5\u00a0days of sepsis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), showed signs of increased lipolysis and ketogenesis, and had higher plasma HDL and LDL lipoprotein concentrations (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01 for all). Muscle fibre type composition was not altered during sepsis, but a higher atrophy sensitivity of type IIb fibres compared with IIa and IIx fibres was observed, independent of obesity or leptin. After 5\u00a0days of critical illness, serum leptin was higher (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and the net waste of nitrogen (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.006) and plasma urea\u2010to\u2010creatinine ratio (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) was lower in overweight\/obese compared with lean ICU human patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Leptin did not mediate the protective effect of obesity against sepsis\u2010induced muscle wasting and weakness in mice. Instead, obesity\u2014independent of leptin\u2014attenuated inflammation, protein catabolism, and dyslipidaemia, pathways that may play a role in the observed muscle protection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12904","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T08:45:30Z","timestamp":1641545130000},"page":"418-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-043X","authenticated-orcid":false,"given":"Wouter","family":"Vankrunkelsven","sequence":"first","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Derde","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-6393","authenticated-orcid":false,"given":"Jan","family":"Gunst","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Vander Perre","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiel","family":"Declerck","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lies","family":"Pauwels","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Derese","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5320-1362","authenticated-orcid":false,"given":"Greet","family":"Van den Berghe","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-6809","authenticated-orcid":false,"given":"Lies","family":"Langouche","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12620"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.278481"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12131"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001310"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31828a2aa1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2506-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12144"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/382250a0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.1.182"},{"key":"e_1_2_8_11_1","first-page":"R136","article-title":"Leptin deficiency enhances sensitivity to endotoxin\u2010induced lethality","volume":"276","author":"Faggioni R","year":"1999","journal-title":"Am J Physiol"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4875-09.2010"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000837"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903975"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006808"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.09.029"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2014.166"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1102662"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012070732"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2809"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.16.3439"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.054"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002520"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602780"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012260605910"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-164152"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.10.008"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2563"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5934"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2364com"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-0014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc12794"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118421"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-019-05760-5"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201702-0354OC"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0715"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31823295e6"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037890"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-211073"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03688-1"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-02860-3"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13081"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12501"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12904","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12904","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12904","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T23:57:04Z","timestamp":1692489424000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1002\/jcsm.12904"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12904","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,7]]},"assertion":[{"value":"2021-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}