title: Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting.
abstract: 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-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-κB) 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-κB 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-κB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Duan
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Shanjun
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Fengchan
authors.initials: F
authors.lastname: Xi
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Juanhong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Weiqin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Wenkui
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, 210002, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000208:Acute Disease; D000818:Animals; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood / Q000150:complications*; D055785:Gene Knockdown Techniques; D007031:Hypothalamus / Q000473:pathology*; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D016086:Lentivirus / Q000378:metabolism; D008070:Lipopolysaccharides; D009133:Muscular Atrophy / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011333:Pro-Opiomelanocortin; D051550:I-kappa B Kinase; D003345:Corticosterone