{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:20Z","timestamp":1787028920409,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Chronic stress induces psychological and physiological changes that may have negative sequelae for health and well-being. In this study, the skeletal muscles of male C57BL\/6 mice subjected to repetitive water-immersion restraint stress to model chronic stress were examined. In chronically stressed mice, serum corticosterone levels significantly increased, whereas thymus volume and bone mineral density decreased. Further, body weight, skeletal muscle mass, and grip strength were significantly decreased. Histochemical analysis of the soleus muscles revealed a significant decrease in the cross-sectional area of type 2b muscle fibers. Although type 2a fibers also tended to decrease, chronic stress had no impact on type 1 muscle fibers. Chronic stress increased the expression of REDD1, FoxO1, FoxO3, KLF15, Atrogin1, and FKBP5, but did not affect the expression of myostatin or myogenin. In contrast, chronic stress resulted in a decrease in p-S6 and p-4E-BP1 levels in the soleus muscle. Taken together, these results indicate that chronic stress promotes muscle atrophy by inhibiting mammalian targets of rapamycin complex 1 activity due to the upregulation of its inhibitor, REDD1.<\/jats:p>","DOI":"10.3390\/medsci11010019","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:33:27Z","timestamp":1675996407000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chronic Stress Induces Type 2b Skeletal Muscle Atrophy via the Inhibition of mTORC1 Signaling in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Shigeko","family":"Fushimi","sequence":"first","affiliation":[{"name":"Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-5603","authenticated-orcid":false,"given":"Tsutomu","family":"Nohno","sequence":"additional","affiliation":[{"name":"Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7387-3089","authenticated-orcid":false,"given":"Hironobu","family":"Katsuyama","sequence":"additional","affiliation":[{"name":"Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","first-page":"36","article-title":"Mechanisms of muscle atrophy induced by glucocorticoids","volume":"72","author":"Schakman","year":"2009","journal-title":"Horm. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C834","DOI":"10.1152\/ajpcell.00579.2003","article-title":"The molecular basis of skeletal muscle atrophy","volume":"287","author":"Jackman","year":"2004","journal-title":"Am. J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1123S","DOI":"10.3945\/ajcn.2010.28608A","article-title":"Skeletal muscle loss: Cachexia, sarcopenia, and inactivity","volume":"91","author":"Evans","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1096\/fba.2018-00080","article-title":"Molecular regulation of skeletal muscle mass and the contribution of nitric oxide: A review","volume":"1","author":"Kobayashi","year":"2019","journal-title":"FASEB BioAdvances"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.1038\/s41467-022-32905-w","article-title":"Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF\/PI3K\/AKT signaling","volume":"13","author":"Mishra","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/jcsm.12677","article-title":"Obestatin signaling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4\/KLF15 axis","volume":"12","author":"Mosteiro","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1152\/japplphysiol.00946.2002","article-title":"Physical performance and soleus muscle fiber composition in wild-derived and laboratory inbred mouse strain","volume":"95","author":"Totsuka","year":"2003","journal-title":"J. Appl. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bone.2016.06.012","article-title":"Evaluating the relationship between muscle and bone modeling response in older adults","volume":"90","author":"Reider","year":"2016","journal-title":"Bone"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"843","DOI":"10.3892\/etm.2015.2621","article-title":"Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain","volume":"10","author":"Katsuyama","year":"2015","journal-title":"Exper. Ther. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s12576-016-0467-y","article-title":"Effect of water-immersion restraint stress on tryptophan catabolism through the kynurenine pathway in rat tissues","volume":"67","author":"Ohta","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s12576-016-0469-9","article-title":"The role of apelin in the healing of water-immersion and restraint stress-induced gastric damage","volume":"67","author":"Birsen","year":"2017","journal-title":"J. Physiol. Sci"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.3389\/fnins.2019.01072","article-title":"Effects of 3 weeks of water immersion and restraint stress on sleep in mice","volume":"13","author":"Yasugaki","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1196\/annals.1410.043","article-title":"Corticotropin-releasing hormone receptor subtypes in the rat anterior pituitary after two types of restraint stress","volume":"1148","author":"Klenerova","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3892\/ijmm_00000360","article-title":"The effect of CAG repeat polymorphism in the glucocorticoid receptor on stress response of mice exposed to water-immersion restraint stress","volume":"25","author":"Tomita","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/gtc.12591","article-title":"Involvement of miR-140-3p in Wnt3a and TGFb3 signaling pathways during osteoblast differentiation in MC3T3-E1 cells","volume":"23","author":"Fushimi","year":"2018","journal-title":"Genes Cells"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1210\/endo.136.12.7588279","article-title":"A long-term increase in basal levels of corticosterone and a decrease in corticosteroid-binding globulin after acute stressor exposure","volume":"136","author":"Fleshner","year":"2015","journal-title":"Endocrinology"},{"key":"ref_17","first-page":"53","article-title":"Forty years of stress research: Principal remaining problems and misconceptions","volume":"115","author":"Selye","year":"1976","journal-title":"Can. Med. Assoc. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1242\/dmm.010389","article-title":"Cellular and molecular mechanisms of muscle atrophy","volume":"6","author":"Bonald","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ncb1101-1014","article-title":"Akt\/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo","volume":"3","author":"Bordine","year":"2001","journal-title":"Nature Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.biocel.2013.05.036","article-title":"Glucocorticoid-induced skeletal muscle atrophy","volume":"45","author":"Schakman","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kang, W., Tong, T., and Park, T. (2020). Corticotropin releasing factor-overexpressing mouse is a model of chronic stress-induced muscle atrophy. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229048"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/ijo.2009.100","article-title":"Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob\/ob) mouse","volume":"33","author":"Kemp","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cbpc.2004.09.021","article-title":"Seven skeletal muscles rich in slow muscle fibers may function to sustain neural position in the rodent hindlimb","volume":"140","author":"Hitomi","year":"2005","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41114","DOI":"10.1074\/jbc.M400674200","article-title":"Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated type I (slow twitch\/red muscle) fiber genes, and impaired glycemic control","volume":"279","author":"Kamei","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nm.3917","article-title":"Myostain is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice","volume":"21","author":"Dankbar","year":"2015","journal-title":"Nature Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R889","DOI":"10.1152\/ajpregu.00296.2010","article-title":"Acute daily psychological stress causes increased atrophic gene expression and myostatin-dependent muscle atrophy","volume":"299","author":"Allen","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1038\/s41467-018-06583-6","article-title":"Myogenin promotes myocyte fusion to balance fibre number and size","volume":"9","author":"Ganassi","year":"2018","journal-title":"Nat. Comm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1210\/en.2008-0038","article-title":"Hypermetabolic syndrome as a consequence of repeated psychological stress in mice","volume":"149","author":"Depke","year":"2008","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1210\/jc.2006-0651","article-title":"Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress","volume":"91","author":"Cree","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.bone.2017.04.006","article-title":"Molecular basis of the crosstalk between bone and muscle","volume":"115","author":"Karsenty","year":"2018","journal-title":"Bone"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/11\/1\/19\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:29:50Z","timestamp":1760120990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/11\/1\/19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["medsci11010019"],"URL":"https:\/\/doi.org\/10.3390\/medsci11010019","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}