Insulin ameliorating endotoxaemia-induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats

Summary Objectives 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. Insuli...

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Published in:Clinical endocrinology (Oxford) 2015-05, Vol.82 (5), p.695-703
Main Authors: Duan, Kaipeng, Yu, Wenkui, Lin, Zhiliang, Tan, Shanjun, Bai, Xiaowu, Gao, Tao, Xi, Fengchan, Li, Ning
Format: Article
Language:English
Subjects:
Agouti-Related Protein - metabolism
Animals
Cytokines - metabolism
Disease Models, Animal
Endotoxemia - complications
Gene Expression Regulation
Hypothalamus - metabolism
Inflammation - metabolism
Insulin - pharmacology
Lipopolysaccharides - chemistry
Male
Muscles - metabolism
Muscles - physiopathology
Neuropeptide Y - metabolism
Neuropeptides - metabolism
Pro-Opiomelanocortin - metabolism
Rats
Rats, Sprague-Dawley
Sepsis - complications
Sepsis - physiopathology
Wasting Syndrome - complications
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Summary:Summary Objectives 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. Design and subjects 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. Conclusion 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.
ISSN:0300-0664
1365-2265
DOI:10.1111/cen.12610