title: Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats.
abstract: In critical patients, sepsis-induced muscle wasting is considered to be an important contributor to complications and mortality. Previous work mainly focuses on the peripheral molecular mechanism of muscle degradation, however little evidence exists for the role of central nervous system in the process. In the present study, we, for the first time, characterized the relationship between muscle wasting and central neuropeptide changes in a septic model. Thirty-six adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) or saline. Twelve, 24 and 48 hrs after injection, skeletal muscle and hypothalamus tissues were harvested. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle ring finger 1 (MuRF-1) and muscle atrophy F-box (MAFbx), as well as 3-methyl-histidine (3-MH) and tyrosine release. Hypothalamic neuropeptides and inflammatory marker expressions were also measured in three time points. LPS injection caused an increase expression of MuRF-1 and MAFbx, and a significant higher release of 3-MH and tyrosine. Hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AgRP) and neuropeptide Y (NPY) presented a dynamic change after LPS injection. Also, hypothalamic inflammatory markers, interleukin-1 β (IL-1β) and tumor necrosis factor α (TNF-α) increased substantially after LPS administration. Importantly, the expressions of POMC, AgRP and CART were well correlated with muscle atrophy gene, MuRF-1 expression. These findings suggest hypothalamic peptides and inflammation may participate in the sepsis-induced muscle wasting, but the exact mechanism needs further study.
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, 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, China. Electronic address: yudrnj@163.com.
authors.forename: Wenkui
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, 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, 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, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, 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, 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, China. Electronic address: liningnju@126.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism; D019446:Endotoxemia; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000139:chemically induced / Q000150:complications
chemical_list: D008070:Lipopolysaccharides; D009124:Muscle Proteins; D009479:Neuropeptides
keywords: Inflammation; Muscle wasting; Neuropeptide; Sepsis