{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:16:57Z","timestamp":1792343817637,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Postoperative sarcopenia is associated with poor outcomes in hospitalized patients. However, few studies have focused on short-term postoperative sarcopenia. Furthermore, the influence of nutritional management using amino acids (AAs) comprising a peripheral parenteral nutrition (PPN) solution and its combination with exercise (Exc) is unclear. Hence, we established a postoperative sarcopenic rat model to evaluate the effects of parenteral AA infusion combined with Exc on skeletal muscles and investigate the underlying mechanisms involved in the amelioration of muscle atrophy. Male F344 rats underwent surgery followed by hindlimb suspension (HS) for 5 days. The rats were divided into AA (\u2212), AA (+), AA (\u2212)-Exc, and AA (+)-Exc groups. They were continuously administered a PPN solution with or without AA at 98 kcal\/kg\/day. The Exc groups were subjected to intermittent loading for 1 h per day. Postoperative sarcopenic rats exhibited decreased muscle strength and mass and an upregulated ubiquitin\u2013proteasome system, autophagy\u2013lysosome system, and fast-twitch fiber-related genes, especially in the AA (\u2212) group. The AA (+)-Exc group exhibited attenuated decreased muscle strength, increased gastrocnemius mass, and a suppressed upregulation of muscle atrophy- and fast-twitch fiber-related genes. Therefore, parenteral AA infusion combined with Exc may be effective in preventing postoperative sarcopenia in hospitalized patients.<\/jats:p>","DOI":"10.3390\/nu16081218","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T06:28:09Z","timestamp":1713508089000},"page":"1218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combination of Parenteral Amino Acid Infusion and Intermittent Loading Exercise Ameliorates Progression of Postoperative Sarcopenia in Rat Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-5766","authenticated-orcid":false,"given":"Akira","family":"Wada","sequence":"first","affiliation":[{"name":"Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan"},{"name":"Department of Innovative Science and Technology for Bio-Industry, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Togashi","sequence":"additional","affiliation":[{"name":"Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arashi","family":"Muroi","sequence":"additional","affiliation":[{"name":"Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-5286","authenticated-orcid":false,"given":"Satoshi","family":"Kido","sequence":"additional","affiliation":[{"name":"Naruto Research Institute, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Furuya","sequence":"additional","affiliation":[{"name":"Department of Innovative Science and Technology for Bio-Industry, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Innovative Bio-Architecture Center, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Environmental Control Center for Experimental Biology, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1016\/S0140-6736(19)31138-9","article-title":"Sarcopenia","volume":"393","author":"Sayer","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.14336\/AD.2017.0315","article-title":"Acute sarcopenia secondary to hospitalisation\u2014An emerging condition affecting older adults","volume":"9","author":"Welch","year":"2018","journal-title":"Aging Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.clnu.2014.12.015","article-title":"Sarcopenia among hospitalized patients\u2014A cross-sectional study","volume":"34","author":"Sousa","year":"2015","journal-title":"Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1093\/gerona\/glw343","article-title":"Prevalence and clinical correlates of sarcopenia, identified according to the EWGSOP definition and diagnostic algorithm, in hospitalized older people: The GLISTEN study","volume":"72","author":"Bianchi","year":"2017","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1016\/j.clnu.2019.08.026","article-title":"Prognostic value of a rapid sarcopenia measure in acutely ill older adults","volume":"39","author":"Aliberti","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"zrad065","DOI":"10.1093\/bjsopen\/zrad065","article-title":"Consensus-defined sarcopenia predicts adverse outcomes after elective abdominal surgery: Meta-analysis","volume":"10","author":"Park","year":"2023","journal-title":"BJS Open."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.21037\/tgh-23-34","article-title":"Long-term impact of sarcopenia in older patients undergoing gastrectomy for gastric cancer: A systematic review and meta-analysis","volume":"26","author":"Terayama","year":"2023","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.surg.2014.04.027","article-title":"Sarcopenia is a predictor of outcomes in very elderly patients undergoing emergency surgery","volume":"156","author":"Du","year":"2014","journal-title":"Surgery"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1097\/TA.0000000000001657","article-title":"Sarcopenia increases risk of long-term mortality in elderly patients undergoing emergency abdominal surgery","volume":"83","author":"Rangel","year":"2017","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/ggi.14366","article-title":"Trajectories of muscle quantity, quality and function measurements in hospitalized older adults","volume":"22","author":"Welch","year":"2022","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/jcsm.12224","article-title":"The incidence of sarcopenia among hospitalized older patients: Results from the Glisten study","volume":"8","author":"Martone","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.1245\/s10434-021-09623-6","article-title":"Relationship between early postoperative change in total psoas muscle area and long-term prognosis in esophagectomy for patients with esophageal cancer","volume":"28","author":"Matsui","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1111\/febs.12253","article-title":"Mechanisms regulating skeletal muscle growth and atrophy","volume":"280","author":"Schiaffino","year":"2013","journal-title":"FEBS J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E469","DOI":"10.1152\/ajpendo.00204.2014","article-title":"Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx\/atrogin-1","volume":"307","author":"Bodine","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1089\/ars.2019.8000","article-title":"Redox control of proteolysis during inactivity-induced skeletal muscle atrophy","volume":"33","author":"Powers","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.1038\/ncomms7670","article-title":"Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy","volume":"6","author":"Milan","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101463","DOI":"10.1016\/j.arr.2021.101463","article-title":"Shared and distinct mechanisms of skeletal muscle atrophy: A narrative review","volume":"71","author":"Wilburn","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.biocel.2013.05.016","article-title":"Muscle type and fiber type specificity in muscle wasting","volume":"45","author":"Ciciliot","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/1747-0080.12608","article-title":"Nutrition interventions implemented in hospital to lower risk of sarcopenia in older adults: A systematic review of randomised controlled trials","volume":"77","author":"Rus","year":"2020","journal-title":"Nutr. Diet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"zraa069","DOI":"10.1093\/bjsopen\/zraa069","article-title":"Interventions to prevent and treat sarcopenia in a surgical population: A systematic review and meta-analysis","volume":"5","author":"Tomassini","year":"2021","journal-title":"BJS Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s12876-023-02755-x","article-title":"Postoperative inpatient exercise facilitates recovery after laparoscopic surgery in colorectal cancer patients: A randomized controlled trial","volume":"23","author":"Min","year":"2023","journal-title":"BMC Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.clnesp.2021.04.006","article-title":"Perioperative peripheral parenteral nutrition to support major gastrointestinal surgery: Expert opinion on treating the right patients at the right time","volume":"43","author":"Senkal","year":"2021","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Berlana, D. (2022). Parenteral nutrition overview. Nutrients, 14.","DOI":"10.3390\/nu14214480"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.21873\/anticanres.15852","article-title":"Impact of amino acids nutrition following gastrectomy in gastric cancer patients","volume":"42","author":"Kikuchi","year":"2022","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/jpen.2472","article-title":"Effects of amino acids and albumin administration on albumin metabolism in surgically stressed rats: A basic nutritional study","volume":"47","author":"Wada","year":"2023","journal-title":"JPEN J. Parenter. Enteral. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1152\/japplphysiol.00969.2001","article-title":"Hindlimb unloading rodent model: Technical aspects","volume":"92","author":"Globus","year":"2002","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Miyatake, S., Hino, K., Natsui, Y., Ebisu, G., and Fujita, S. (2020). Protein supplementation enhances the effects of intermittent loading on skeletal muscles by activating the mTORC1 signaling pathway in a rat model of disuse atrophy. Nutrients, 12.","DOI":"10.3390\/nu12092729"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1113\/expphysiol.2014.079988","article-title":"Amelioration of capillary regression and atrophy of the soleus muscle in hindlimb-unloaded rats by astaxanthin supplementation and intermittent loading","volume":"99","author":"Kanazashi","year":"2014","journal-title":"Exp. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S0271-5317(02)00427-X","article-title":"The optimal nitrogen proportion to non-protein calories in normal rats receiving hypocaloric parenteral nutrition","volume":"22","author":"Nakayama","year":"2002","journal-title":"Nutr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1271\/bbb.120737","article-title":"Differential dose response of mTOR signaling to oral administration of leucine in skeletal muscle and liver of rats","volume":"77","author":"Yoshizawa","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mantuano, P., Boccanegra, B., Bianchini, G., Cappellari, O., Tulimiero, L., Conte, E., Cirmi, S., Sanarica, F., De Bellis, M., and Mele, A. (2023). Branched-chain amino acids and di-alanine supplementation in aged mice: A translational study on sarcopenia. Nutrients, 15.","DOI":"10.3390\/nu15020330"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jamda.2019.12.012","article-title":"Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment","volume":"21","author":"Chen","year":"2020","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/apha.12190","article-title":"Substantial skeletal muscle loss occurs during only 5 days of disuse","volume":"210","author":"Wall","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"C422","DOI":"10.1152\/ajpcell.00240.2012","article-title":"Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle","volume":"304","author":"Vainshtein","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E899","DOI":"10.1152\/ajpendo.00161.2019","article-title":"Loss of mitochondrial energetics is associated with poor recovery of muscle function but not mass following disuse atrophy","volume":"317","author":"Trevino","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1113\/jphysiol.2012.240267","article-title":"The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms","volume":"590","author":"Brocca","year":"2012","journal-title":"J. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"638983","DOI":"10.3389\/fphys.2021.638983","article-title":"The role of autophagy in skeletal muscle diseases","volume":"12","author":"Xia","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.ajpath.2022.09.003","article-title":"Forkhead Box O signaling pathway in skeletal muscle atrophy","volume":"192","author":"Chen","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1700287","DOI":"10.1002\/mnfr.201700287","article-title":"Fast digestive, leucine-rich, soluble milk proteins improve muscle protein anabolism, and mitochondrial function in undernourished old rats","volume":"61","author":"Salles","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/270174a0","article-title":"Induction of autophagy by amino-acid deprivation in perfused rat liver","volume":"270","author":"Mortimore","year":"1977","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8192","DOI":"10.1021\/acs.jafc.5b03811","article-title":"Dietary L-lysine suppresses autophagic proteolysis and stimulates Akt\/mTOR signaling in the skeletal muscle of rats fed a low-protein diet","volume":"63","author":"Sato","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1002\/mnfr.201300758","article-title":"Dietary deprivation of each essential amino acid induces differential systemic adaptive responses in mice","volume":"58","author":"Kamata","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E594","DOI":"10.1152\/ajpendo.00257.2016","article-title":"Control of skeletal muscle atrophy in response to disuse: Clinical\/preclinical contentions and fallacies of evidence","volume":"311","author":"Atherton","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1113\/jphysiol.2003.044701","article-title":"Global analysis of gene expression patterns during disuse atrophy in rat skeletal muscle","volume":"551","author":"Stevenson","year":"2003","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E86","DOI":"10.1152\/ajpendo.00261.2018","article-title":"Acute recovery from disuse atrophy: The role of stretch-activated ion channels in the activation of anabolic signaling in skeletal muscle","volume":"316","author":"Mirzoev","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9806","DOI":"10.1038\/s41598-021-89362-6","article-title":"Plantar mechanical stimulation attenuates protein synthesis decline in disused skeletal muscle via modulation of nitric oxide level","volume":"11","author":"Tyganov","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1152\/japplphysiol.00137.2018","article-title":"Exercise preconditioning diminishes skeletal muscle atrophy after hindlimb suspension in mice","volume":"125","author":"Theilen","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Vilchinskaya, N., Altaeva, E., and Lomonosova, Y. (2022). Gaining insight into the role of FoxO1 in the progression of disuse-induced skeletal muscle atrophy. Adv. Biol. Regul., 85.","DOI":"10.1016\/j.jbior.2022.100903"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ijge.2018.03.003","article-title":"Plasma amino acid profile in severely frail elderly patients in Japan","volume":"12","author":"Adachi","year":"2018","journal-title":"Int. J. Gerontol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Toyoshima, K., Nakamura, M., Adachi, Y., Imaizumi, A., Hakamada, T., Abe, Y., Kaneko, E., Takahashi, S., and Shimokado, K. (2017). Increased plasma proline concentrations are associated with sarcopenia in the elderly. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185206"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s004180050341","article-title":"Fiber type composition of four hindlimb muscles of adult Fisher 344 rats","volume":"111","author":"Staron","year":"1999","journal-title":"Histochem Cell Biol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/8\/1218\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:30:54Z","timestamp":1760106654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/8\/1218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,19]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["nu16081218"],"URL":"https:\/\/doi.org\/10.3390\/nu16081218","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,19]]}}}