title: Insulin ameliorating endotoxaemia-induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats.
abstract: OBJECTIVE
  Septic patients always develop muscle wasting, which delays the rehabilitation and contributes to the increased complications and mortality. Previous studies have implied the crucial role of central inflammation and neuropeptides in the energy balance and muscle metabolism. Insulin has been confirmed to attenuate muscle degradation and inhibit inflammation. We tested the hypothesis whether insulin ameliorating muscle wasting was associated with modulating hypothalamic inflammation and neuropeptides.
  
  
  METHODS
  Thirty-two adult male Sprague-Dawley rats were in intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by subcutaneous injection of insulin (5 IU/kg) or saline. Twenty-four hours 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-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also measured in four groups.
  
  
  RESULTS
  LPS injection led to significant increase in hypothalamic inflammation as well as muscle wasting. Also, increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were observed. Insulin treatment ameliorated endotoxaemia-induced muscle wasting and hypothalamic inflammation, and attenuated the alteration of neuropeptides, POMC, CART and AgRP.
  
  
  CONCLUSIONS
  Hypothalamic inflammation and neuropeptides are involved in the endotoxaemia-induced muscle wasting. Insulin treatment can reduce muscle wasting, which is associated with reduced hypothalamic inflammation and alteration of hypothalamic neuropeptides.
authors.affiliation: Department of General Surgery, Jinling hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Duan
authors.forename: Wenkui
authors.initials: W
authors.lastname: Yu
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Lin
authors.forename: Shanjun
authors.initials: S
authors.lastname: Tan
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Bai
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.forename: Fengchan
authors.initials: F
authors.lastname: Xi
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications*; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D009132:Muscles / Q000378:metabolism / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000503:physiopathology; D019282:Wasting Syndrome / Q000150:complications*
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D016207:Cytokines; D007328:Insulin; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D009479:Neuropeptides; D011333:Pro-Opiomelanocortin