{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:00:32Z","timestamp":1779177632223,"version":"3.51.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T00:00:00Z","timestamp":1480982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T00:00:00Z","timestamp":1480982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-\u03baB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-\u03baB) pathway activation by infusion of an inhibitor (PS1145) can efficiently reduce muscle wasting as well as attenuate hypothalamic neuropeptides alteration. Furthermore, knockdown the expression of anorexigenic neuropeptide proopiomelanocortin (POMC) expression with a lentiviral vector containing shRNA can significantly alleviate LPS-induced muscle wasting, whereas hypothalamic inflammation or NF-\u03baB pathway was barely affected. Taken together, these results suggest activation of hypothalamic POMC is pivotal for acute muscle wasting caused by endotoxemia. Neuropeptide POMC expression may have mediated the contribution of hypothalamic inflammation to peripheral muscle wasting. Pharmaceuticals with the ability of inhibiting hypothalamic NF-\u03baB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.<\/jats:p>","DOI":"10.1038\/srep38544","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T10:20:44Z","timestamp":1481019644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting"],"prefix":"10.1038","volume":"6","author":[{"given":"Kaipeng","family":"Duan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minhua","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiliang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanjun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengchan","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialiang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanhong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenkui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieshou","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,6]]},"reference":[{"key":"BFsrep38544_CR1","doi-asserted-by":"publisher","first-page":"S69","DOI":"10.1086\/367561","volume":"36","author":"S Grinspoon","year":"2003","unstructured":"Grinspoon, S. et al. Weight loss and wasting in patients infected with human immunodeficiency virus. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 36, S69\u201378, doi: 10.1086\/367561 (2003).","journal-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America"},{"key":"BFsrep38544_CR2","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1056\/NEJMoa1102662","volume":"365","author":"MP Casaer","year":"2011","unstructured":"Casaer, M. P. et al. Early versus late parenteral nutrition in critically ill adults. The New England journal of medicine 365, 506\u2013517, doi: 10.1056\/NEJMoa1102662 (2011).","journal-title":"The New England journal of medicine"},{"key":"BFsrep38544_CR3","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1001\/jama.2012.137","volume":"307","author":"L National Heart","year":"2012","unstructured":"National Heart, L. et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA: the journal of the American Medical Association 307, 795\u2013803, doi: 10.1001\/jama.2012.137 (2012).","journal-title":"JAMA: the journal of the American Medical Association"},{"key":"BFsrep38544_CR4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S2213-2600(13)70262-5","volume":"2","author":"DE Bear","year":"2014","unstructured":"Bear, D. E., Puthucheary, Z. A. & Hart, N. Early feeding during critical illness. The lancet. Respiratory medicine 2, 15\u201317, doi: 10.1016\/S2213-2600(13)70262-5 (2014).","journal-title":"The lancet. Respiratory medicine"},{"key":"BFsrep38544_CR5","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/S2213-2600(13)70183-8","volume":"1","author":"G Hermans","year":"2013","unstructured":"Hermans, G. et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. The lancet. Respiratory medicine 1, 621\u2013629, doi: 10.1016\/S2213-2600(13)70183-8 (2013).","journal-title":"The lancet. Respiratory medicine"},{"key":"BFsrep38544_CR6","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1001\/jama.2013.278481","volume":"310","author":"ZA Puthucheary","year":"2013","unstructured":"Puthucheary, Z. A. et al. Acute skeletal muscle wasting in critical illness. Jama 310, 1591\u20131600, doi: 10.1001\/jama.2013.278481 (2013).","journal-title":"Jama"},{"key":"BFsrep38544_CR7","doi-asserted-by":"publisher","first-page":"R12","DOI":"10.1186\/cc13189","volume":"18","author":"PJ Weijs","year":"2014","unstructured":"Weijs, P. J. et al. Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients. Critical care 18, R12, doi: 10.1186\/cc13189 (2014).","journal-title":"Critical care"},{"key":"BFsrep38544_CR8","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.cell.2010.07.011","volume":"142","author":"X Zhou","year":"2010","unstructured":"Zhou, X. et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 142, 531\u2013543, doi: 10.1016\/j.cell.2010.07.011 (2010).","journal-title":"Cell"},{"key":"BFsrep38544_CR9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1242\/dmm.010389","volume":"6","author":"P Bonaldo","year":"2013","unstructured":"Bonaldo, P. & Sandri, M. Cellular and molecular mechanisms of muscle atrophy. Disease models & mechanisms 6, 25\u201339, doi: 10.1242\/dmm.010389 (2013).","journal-title":"Disease models & mechanisms"},{"key":"BFsrep38544_CR10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.cell.2008.07.043","volume":"135","author":"X Zhang","year":"2008","unstructured":"Zhang, X. et al. Hypothalamic IKKbeta\/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135, 61\u201373, doi: 10.1016\/j.cell.2008.07.043 (2008).","journal-title":"Cell"},{"key":"BFsrep38544_CR11","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1111\/j.1749-6632.2011.06388.x","volume":"1243","author":"D Cai","year":"2011","unstructured":"Cai, D. & Liu, T. Hypothalamic inflammation: a double-edged sword to nutritional diseases. Annals of the New York Academy of Sciences 1243, E1\u201339, doi: 10.1111\/j.1749-6632.2011.06388.x (2011).","journal-title":"Annals of the New York Academy of Sciences"},{"key":"BFsrep38544_CR12","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nature05026","volume":"443","author":"GJ Morton","year":"2006","unstructured":"Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S. & Schwartz, M. W. Central nervous system control of food intake and body weight. Nature 443, 289\u2013295, doi: 10.1038\/nature05026 (2006).","journal-title":"Nature"},{"key":"BFsrep38544_CR13","first-page":"1432","volume":"61","author":"DL Marks","year":"2001","unstructured":"Marks, D. L., Ling, N. & Cone, R. D. Role of the central melanocortin system in cachexia. Cancer research 61, 1432\u20131438 (2001).","journal-title":"Cancer research"},{"key":"BFsrep38544_CR14","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1084\/jem.20111020","volume":"208","author":"TP Braun","year":"2011","unstructured":"Braun, T. P. et al. Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. The Journal of experimental medicine 208, 2449\u20132463, doi: 10.1084\/jem.20111020 (2011).","journal-title":"The Journal of experimental medicine"},{"key":"BFsrep38544_CR15","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.physbeh.2010.03.011","volume":"100","author":"AJ Grossberg","year":"2010","unstructured":"Grossberg, A. J., Scarlett, J. M. & Marks, D. L. Hypothalamic mechanisms in cachexia. Physiology & behavior 100, 478\u2013489, doi: 10.1016\/j.physbeh.2010.03.011 (2010).","journal-title":"Physiology & behavior"},{"key":"BFsrep38544_CR16","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.nut.2009.07.003","volume":"26","author":"MD DeBoer","year":"2010","unstructured":"DeBoer, M. D. Update on melanocortin interventions for cachexia: progress toward clinical application. Nutrition 26, 146\u2013151, doi: 10.1016\/j.nut.2009.07.003 (2010).","journal-title":"Nutrition"},{"key":"BFsrep38544_CR17","doi-asserted-by":"publisher","first-page":"F1315","DOI":"10.1152\/ajprenal.00341.2012","volume":"303","author":"WW Cheung","year":"2012","unstructured":"Cheung, W. W. & Mak, R. H. Melanocortin antagonism ameliorates muscle wasting and inflammation in chronic kidney disease. American journal of physiology. Renal physiology 303, F1315\u20131324, doi: 10.1152\/ajprenal.00341.2012 (2012).","journal-title":"American journal of physiology. Renal physiology"},{"key":"BFsrep38544_CR18","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","volume":"132","author":"MS Hayden","year":"2008","unstructured":"Hayden, M. S. & Ghosh, S. Shared principles in NF-kappaB signaling. Cell 132, 344\u2013362, doi: 10.1016\/j.cell.2008.01.020 (2008).","journal-title":"Cell"},{"key":"BFsrep38544_CR19","doi-asserted-by":"publisher","first-page":"9706","DOI":"10.1074\/jbc.M109.070706","volume":"285","author":"PG Jang","year":"2010","unstructured":"Jang, P. G. et al. NF-kappaB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia. The Journal of biological chemistry 285, 9706\u20139715, doi: 10.1074\/jbc.M109.070706 (2010).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep38544_CR20","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1042\/CS20070105","volume":"113","author":"AP Coll","year":"2007","unstructured":"Coll, A. P. Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential? Clinical science 113, 171\u2013182, doi: 10.1042\/CS20070105 (2007).","journal-title":"Clinical science"},{"key":"BFsrep38544_CR21","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.yfrne.2009.10.002","volume":"31","author":"JP Thaler","year":"2010","unstructured":"Thaler, J. P., Choi, S. J., Schwartz, M. W. & Wisse, B. E. Hypothalamic inflammation and energy homeostasis: resolving the paradox. Frontiers in neuroendocrinology 31, 79\u201384, doi: 10.1016\/j.yfrne.2009.10.002 (2010).","journal-title":"Frontiers in neuroendocrinology"},{"key":"BFsrep38544_CR22","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1097\/SPC.0b013e32833e48e7","volume":"4","author":"SM Krasnow","year":"2010","unstructured":"Krasnow, S. M. & Marks, D. L. Neuropeptides in the pathophysiology and treatment of cachexia. Current opinion in supportive and palliative care 4, 266\u2013271, doi: 10.1097\/SPC.0b013e32833e48e7 (2010).","journal-title":"Current opinion in supportive and palliative care"},{"key":"BFsrep38544_CR23","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1210\/en.2009-0865","volume":"151","author":"AP Arruda","year":"2010","unstructured":"Arruda, A. P. et al. Hypothalamic actions of tumor necrosis factor alpha provide the thermogenic core for the wastage syndrome in cachexia. Endocrinology 151, 683\u2013694, doi: 10.1210\/en.2009-0865 (2010).","journal-title":"Endocrinology"},{"key":"BFsrep38544_CR24","doi-asserted-by":"publisher","first-page":"5230","DOI":"10.1210\/en.2007-0394","volume":"148","author":"BE Wisse","year":"2007","unstructured":"Wisse, B. E. et al. Evidence that lipopolysaccharide-induced anorexia depends upon central, rather than peripheral, inflammatory signals. Endocrinology 148, 5230\u20135237, doi: 10.1210\/en.2007-0394 (2007).","journal-title":"Endocrinology"},{"key":"BFsrep38544_CR25","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1523\/JNEUROSCI.4268-04.2005","volume":"25","author":"S Chakravarty","year":"2005","unstructured":"Chakravarty, S. & Herkenham, M. Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. The Journal of neuroscience: the official journal of the Society for Neuroscience 25, 1788\u20131796, doi: 10.1523\/JNEUROSCI.4268-04.2005 (2005).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep38544_CR26","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","volume":"27","author":"WJ Evans","year":"2008","unstructured":"Evans, W. J. et al. Cachexia: a new definition. Clinical nutrition 27, 793\u2013799, doi: 10.1016\/j.clnu.2008.06.013 (2008).","journal-title":"Clinical nutrition"},{"key":"BFsrep38544_CR27","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.cell.2004.09.027","volume":"119","author":"D Cai","year":"2004","unstructured":"Cai, D. et al. IKKbeta\/NF-kappaB activation causes severe muscle wasting in mice. Cell 119, 285\u2013298, doi: 10.1016\/j.cell.2004.09.027 (2004).","journal-title":"Cell"},{"key":"BFsrep38544_CR28","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.peptides.2007.03.006","volume":"28","author":"T Romanatto","year":"2007","unstructured":"Romanatto, T. et al. TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient\u2013effects on leptin and insulin signaling pathways. Peptides 28, 1050\u20131058, doi: 10.1016\/j.peptides.2007.03.006 (2007).","journal-title":"Peptides"},{"key":"BFsrep38544_CR29","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/cen.12610","volume":"82","author":"K Duan","year":"2015","unstructured":"Duan, K. et al. Insulin ameliorating endotoxaemia-induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats. Clinical endocrinology 82, 695\u2013703, doi: 10.1111\/cen.12610 (2015).","journal-title":"Clinical endocrinology"},{"key":"BFsrep38544_CR30","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0092-8674(00)81865-6","volume":"88","author":"D Huszar","year":"1997","unstructured":"Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131\u2013141 (1997).","journal-title":"Cell"},{"key":"BFsrep38544_CR31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/79254","volume":"26","author":"AS Chen","year":"2000","unstructured":"Chen, A. S. et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nature genetics 26, 97\u2013102, doi: 10.1038\/79254 (2000).","journal-title":"Nature genetics"},{"key":"BFsrep38544_CR32","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1677\/JOE-09-0397","volume":"206","author":"JM Scarlett","year":"2010","unstructured":"Scarlett, J. M. et al. Genetic and pharmacologic blockade of central melanocortin signaling attenuates cardiac cachexia in rodent models of heart failure. The Journal of endocrinology 206, 121\u2013130, doi: 10.1677\/JOE-09-0397 (2010).","journal-title":"The Journal of endocrinology"},{"key":"BFsrep38544_CR33","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.npep.2014.10.002","volume":"48","author":"K Duan","year":"2014","unstructured":"Duan, K. et al. Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats. Neuropeptides 48, 379\u2013386, doi: 10.1016\/j.npep.2014.10.002 (2014).","journal-title":"Neuropeptides"},{"key":"BFsrep38544_CR34","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.mce.2009.08.007","volume":"314","author":"EA Roman","year":"2010","unstructured":"Roman, E. A. et al. Central leptin action improves skeletal muscle AKT, AMPK, and PGC1 alpha activation by hypothalamic PI3K-dependent mechanism. Molecular and cellular endocrinology 314, 62\u201369, doi: 10.1016\/j.mce.2009.08.007 (2010).","journal-title":"Molecular and cellular endocrinology"},{"key":"BFsrep38544_CR35","doi-asserted-by":"publisher","first-page":"3572","DOI":"10.1096\/fj.13-230375","volume":"27","author":"TP Braun","year":"2013","unstructured":"Braun, T. P. et al. Cancer- and endotoxin-induced cachexia require intact glucocorticoid signaling in skeletal muscle. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 27, 3572\u20133582, doi: 10.1096\/fj.13-230375 (2013).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"BFsrep38544_CR36","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1172\/JCI31743","volume":"117","author":"R Nogueiras","year":"2007","unstructured":"Nogueiras, R. et al. The central melanocortin system directly controls peripheral lipid metabolism. The Journal of clinical investigation 117, 3475\u20133488, doi: 10.1172\/JCI31743 (2007).","journal-title":"The Journal of clinical investigation"},{"key":"BFsrep38544_CR37","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1210\/jc.2009-2297","volume":"95","author":"F Sayk","year":"2010","unstructured":"Sayk, F. et al. Sympathetic function in human carriers of melanocortin-4 receptor gene mutations. The Journal of clinical endocrinology and metabolism 95, 1998\u20132002, doi: 10.1210\/jc.2009-2297 (2010).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"BFsrep38544_CR38","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s00109-009-0547-z","volume":"88","author":"G Mantovani","year":"2010","unstructured":"Mantovani, G. et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. Journal of molecular medicine 88, 85\u201392, doi: 10.1007\/s00109-009-0547-z (2010).","journal-title":"Journal of molecular medicine"},{"key":"BFsrep38544_CR39","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1093\/ajcn\/84.6.1463","volume":"84","author":"SM Marcora","year":"2006","unstructured":"Marcora, S. M., Chester, K. R., Mittal, G., Lemmey, A. B. & Maddison, P. J. Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis. The American journal of clinical nutrition 84, 1463\u20131472 (2006).","journal-title":"The American journal of clinical nutrition"},{"key":"BFsrep38544_CR40","doi-asserted-by":"publisher","first-page":"E1003","DOI":"10.1152\/ajpendo.90377.2008","volume":"296","author":"KA Posey","year":"2009","unstructured":"Posey, K. A. et al. Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. American journal of physiology. Endocrinology and metabolism 296, E1003\u20131012, doi: 10.1152\/ajpendo.90377.2008 (2009).","journal-title":"American journal of physiology. Endocrinology and metabolism"},{"key":"BFsrep38544_CR41","doi-asserted-by":"publisher","first-page":"e3856","DOI":"10.1371\/journal.pone.0003856","volume":"3","author":"ER Ropelle","year":"2008","unstructured":"Ropelle, E. R. et al. Central exercise action increases the AMPK and mTOR response to leptin. PloS one 3, e3856, doi: 10.1371\/journal.pone.0003856 (2008).","journal-title":"PloS one"},{"key":"BFsrep38544_CR42","doi-asserted-by":"publisher","first-page":"4084","DOI":"10.1210\/en.2004-0592","volume":"145","author":"MG Jeschke","year":"2004","unstructured":"Jeschke, M. G., Klein, D., Bolder, U. & Einspanier, R. Insulin attenuates the systemic inflammatory response in endotoxemic rats. Endocrinology 145, 4084\u20134093, doi: 10.1210\/en.2004-0592 (2004).","journal-title":"Endocrinology"},{"key":"BFsrep38544_CR43","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1476-9255-8-13","volume":"8","author":"Q Chen","year":"2011","unstructured":"Chen, Q. et al. Insulin alleviates degradation of skeletal muscle protein by inhibiting the ubiquitin-proteasome system in septic rats. Journal of inflammation 8, 13, doi: 10.1186\/1476-9255-8-13 (2011).","journal-title":"Journal of inflammation"},{"key":"BFsrep38544_CR44","doi-asserted-by":"publisher","first-page":"R893","DOI":"10.1152\/ajpregu.00015.2008","volume":"296","author":"A Balasubramaniam","year":"2009","unstructured":"Balasubramaniam, A. et al. Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx. American journal of physiology. Regulatory, integrative and comparative physiology 296, R893\u2013901, doi: 10.1152\/ajpregu.00015.2008 (2009).","journal-title":"American journal of physiology. Regulatory, integrative and comparative physiology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep38544.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep38544","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep38544.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:29:25Z","timestamp":1672878565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep38544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,6]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep38544"],"URL":"https:\/\/doi.org\/10.1038\/srep38544","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,6]]},"assertion":[{"value":"4 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38544"}}