{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:24:01Z","timestamp":1790767441009,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000033","name":"Institute of Musculoskeletal Health and Arthritis","doi-asserted-by":"publisher","award":["PJT156060"],"award-info":[{"award-number":["PJT156060"]}],"id":[{"id":"10.13039\/501100000033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002160","name":"Jain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Most mouse models of muscular dystrophy (MD) show mild phenotypes, which limits the translatability of experimental therapies to patients. A growing body of evidence suggests that MD is accompanied by metabolic abnormalities that could potentially exacerbate the primary muscle wasting process. Since thermoneutral (TN) housing of mice (~30\u00b0C) has been shown to affect many metabolic parameters, particularly when combined with a Western diet (WD), our aim was to determine whether the combination of TN and WD exacerbates muscle wasting in dysferlin\u2010deficient BLAJ mice, a common model of limb\u2010girdle MD type 2b (LGMD2b).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 2\u2010mo\u2010old wild\u2010type (WT) and BLAJ mice were housed at TN or room temperature (RT) and fed a WD or regular chow for 9\u2009mo. Ambulatory function, muscle histology, and protein immunoblots of skeletal muscle were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BLAJ mice at RT and fed a chow diet showed normal ambulation function similar to WT mice, whereas 90% of BLAJ mice under WD and TN combination showed ambulatory dysfunction (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and an up to 4.1\u2010fold increase in quadriceps and gastrocnemius fat infiltration. Western blotting revealed decreased autophagy marker microtubules\u2010associated protein 1 light chain 3\u2010B (LC3BII\/LC3BI) ratio and up\u2010regulation of protein kinase B\/AKT and ribosomal protein S6 phosphorylation, suggesting inefficient cellular debris and protein clearance in TN BLAJ mice fed a WD. Male and female BLAJ mice under TN and WD combination showed heterogenous fibro\u2010fatty infiltrate composition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>TN and WD combination exacerbates rodent LGMD2b without affecting WT mice. This improves rodent modeling of human MD and helps elucidate how metabolic abnormalities may play a causal role in muscle wasting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27680","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T05:39:08Z","timestamp":1658381948000},"page":"513-522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Thermoneutral Housing and a Western Diet Combination Exacerbates <scp>Dysferlin\u2010Deficient<\/scp> Muscular Dystrophy"],"prefix":"10.1002","volume":"66","author":[{"given":"Graham S.","family":"Donen","sequence":"first","affiliation":[{"name":"University of British Columbia (UBC) Department of Anesthesiology, Pharmacology &amp; Therapeutics  Vancouver Canada"},{"name":"UBC Centre for Heart Lung Innovation St. Paul's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"White","sequence":"additional","affiliation":[{"name":"University of British Columbia (UBC) Department of Anesthesiology, Pharmacology &amp; Therapeutics  Vancouver Canada"},{"name":"UBC Centre for Heart Lung Innovation St. Paul's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Sauge","sequence":"additional","affiliation":[{"name":"University of British Columbia (UBC) Department of Anesthesiology, Pharmacology &amp; Therapeutics  Vancouver Canada"},{"name":"UBC Centre for Heart Lung Innovation St. Paul's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Ritso","sequence":"additional","affiliation":[{"name":"The Biomedical Research Centre UBC  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Theret","sequence":"additional","affiliation":[{"name":"The Biomedical Research Centre UBC  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Boyd","sequence":"additional","affiliation":[{"name":"UBC Centre for Heart Lung Innovation St. Paul's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Devlin","sequence":"additional","affiliation":[{"name":"University of British Columbia (UBC) Department of Pediatrics, BC Children's Hospital Research Institute  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio M. V.","family":"Rossi","sequence":"additional","affiliation":[{"name":"The Biomedical Research Centre UBC  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3198-1548","authenticated-orcid":false,"given":"Pascal","family":"Bernatchez","sequence":"additional","affiliation":[{"name":"University of British Columbia (UBC) Department of Anesthesiology, Pharmacology &amp; Therapeutics  Vancouver Canada"},{"name":"UBC Centre for Heart Lung Innovation St. Paul's Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01573"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M079459"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-017-0135-9"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.48"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2016.09.008"},{"key":"e_1_2_12_7_1","article-title":"Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality","volume":"294","author":"Swoap SJ","year":"2008","journal-title":"Am J Physiol"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278221"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.675322"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.112.171967"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-157-4_4"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031057"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.02.004"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5704"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108624"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a071674"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.RA119000399"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2672"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.04.024"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.159"},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2014.00230","article-title":"The intriguing regulators of muscle mass in sarcopenia and muscular dystrophy","volume":"6","author":"Sakuma K","year":"2014","journal-title":"Front Aging Neurosci"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00075197-200111000-00006"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.10.018"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27680","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.27680","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27680","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T14:05:04Z","timestamp":1692626704000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.27680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/mus.27680"],"URL":"https:\/\/doi.org\/10.1002\/mus.27680","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]},"assertion":[{"value":"2021-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}