{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:37:50Z","timestamp":1792442270464,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Systemic inflammation is associated with skeletal muscle atrophy and metabolic dysfunction. Although the nucleotide\u2010binding oligomerization domain\u2010like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cytokine production in immune cells, its role in skeletal muscle is poorly understood. Here, we studied the link between inflammation, NLRP3, muscle morphology, and metabolism in\n                      <jats:italic>in vitro<\/jats:italic>\n                      cultured C2C12 myotubes, independent of immune cell involvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentiated C2C12 myotubes were treated with lipopolysaccharide (LPS; 0, 10, and 100\u2013200\u00a0ng\/mL) to induce activation of the NLRP3 inflammasome with and without MCC950, a pharmacological inhibitor of NLRP3\u2010induced IL\u20101\u03b2 production. We assessed markers of the NLRP3 inflammasome, cell diameter, reactive oxygen species, and mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NLRP3 gene expression and protein concentrations increased in a time\u2010dependent and dose\u2010dependent manner. Intracellular IL\u20101\u03b2 concentration significantly increased (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001), but significantly less with MCC950 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03), suggestive of moderate activation of the NLRP3 inflammasome in cultured myotubes upon LPS stimulation. LPS suppressed myotube growth after 24\u00a0h (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03), and myotubes remained smaller up to 72\u00a0h (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0009). Exposure of myotubes to IL\u20101\u03b2 caused similar alterations in cell morphology, and\u00a0MCC950 mitigated these LPS\u2010induced differences in cell diameter. NLRP3 appeared to co\u2010localize with mitochondria, more so upon exposure to LPS. Mitochondrial reactive oxygen species were higher after LPS (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03), but not after addition of MCC950. Myotubes had higher glycolytic rates, and mitochondria were more fragmented upon LPS exposure, which was not altered by MCC950 supplementation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LPS\u2010induced activation of the NLRP3 inflammasome in cultured myotubes contributes to morphological and metabolic alterations, likely due to its mitochondrial association.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13062","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T23:20:17Z","timestamp":1660778417000},"page":"3048-3061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["The NLRP3 inflammasome contributes to inflammation\u2010induced morphological and metabolic alterations in skeletal muscle"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-4063","authenticated-orcid":false,"given":"Moritz","family":"Eggelbusch","sequence":"first","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"},{"name":"Department of Nutrition and Dietetics, Amsterdam UMC location VUmc Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"},{"name":"Faculty of Sports and Nutrition, Center of Expertise Urban Vitality Amsterdam University of Applied Sciences  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi","family":"Shi","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"},{"name":"Department of Oral and Maxillofacial Surgery\/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"},{"name":"Department of Prosthodontics Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie C.","family":"Broeksma","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"V\u00e1zquez\u2010Cruz","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madu N.","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard M. J.","family":"de Wit","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-5131","authenticated-orcid":false,"given":"Bart","family":"Everts","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center University of Leiden  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-0952","authenticated-orcid":false,"given":"Richard T.","family":"Jaspers","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"},{"name":"Department of Prosthodontics Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-5177","authenticated-orcid":false,"given":"Rob C.I.","family":"W\u00fcst","sequence":"additional","affiliation":[{"name":"Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"42","article-title":"Regular physical exercise mediates the immune response in 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