{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:58:23Z","timestamp":1791845903337,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["POST903198"],"award-info":[{"award-number":["POST903198"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["POST836216"],"award-info":[{"award-number":["POST836216"]}],"id":[{"id":"10.13039\/100000968","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":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle\u2010specific AHR knockout mice exposed to chronic repeated (5\u00a0days per week for 16\u00a0weeks) cigarette smoke and skeletal muscle\u2010specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Skeletal muscle from COPD patients (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a079, age\u00a0=\u00a067.0\u00a0\u00b1\u00a08.4\u00a0years) had higher levels of\n                      <jats:italic>AHR<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0451) and\n                      <jats:italic>CYP1B1<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) compared to healthy adult controls (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a016, age\u00a0=\u00a066.5\u00a0\u00b1\u00a06.5\u00a0years). Mice exposed to cigarette smoke displayed higher expression of\n                      <jats:italic>Ahr<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.008),\n                      <jats:italic>Cyp1b1<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001), and\n                      <jats:italic>Cyp1a1<\/jats:italic>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) in skeletal muscle compared to air controls. Cigarette smoke exposure was found to impair skeletal muscle mitochondrial oxidative phosphorylation by ~50% in littermate controls (Treatment effect,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), which was attenuated by deletion of the AHR in muscle in male (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001), but not female, mice (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.37), indicating there are sex\u2010dependent pathological effects of smoking\u2010induced AHR activation in skeletal muscle. Viral mediated expression of a constitutively active mutant AHR in the muscle of healthy mice recapitulated the effects of cigarette smoking by decreasing muscle mitochondrial oxidative phosphorylation by ~40% (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings provide evidence linking chronic AHR activation secondary to cigarette smoke exposure to skeletal muscle bioenergetic deficits in male, but not female, mice. AHR activation is a likely contributor to the decline in muscle oxidative capacity observed in smokers and AHR antagonism may provide a therapeutic avenue aimed to improve muscle function in COPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13439","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T04:13:53Z","timestamp":1707452033000},"page":"646-659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Chronic aryl hydrocarbon receptor activity impairs muscle mitochondrial function with tobacco smoking"],"prefix":"10.1002","volume":"15","author":[{"given":"Liam F.","family":"Fitzgerald","sequence":"first","affiliation":[{"name":"Department of Physical Therapy University of Florida  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Lackey","sequence":"additional","affiliation":[{"name":"Department of Applied 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