Abstract
To investigate whether exogenous melatonin (MLT) could alleviate skeletal muscle wasting by regulating hypothalamic neuropeptides expression. Adult male Sprague Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg), followed by MLT (30 mg/kg/day) or saline for 3 days. Hypothalamic tissues and skeletal muscle were obtained on day 3. Skeletal muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box and muscle ring finger 1 as well as 3-methylhistidine (3-MH) and tyrosine release. Three hypothalamic neuropeptides (POMC, AgRP, CART) expression were detected in all groups. POMC expression knockdown was achieved by ARC injection of lentiviruses containing shRNA against POMC. Two weeks after ARC viruses injection, rats were i.p. injected with LPS (10 mg/kg) followed by MLT (30 mg/kg/day) or saline for 3 days. Brain tissues were harvested for immunostaining. In septic rats, 3-MH, tyrosine release and muscle atrophic gene expression were significantly decreased in MLT treated group. POMC and CART expression were lower while AgRP expression was higher in MLT treated group. Furthermore, in septic rats treated with MLT, muscle wasting in those with lower expression of neuropeptide POMC did not differ from those with normal POMC expression. Exogenous MLT could alleviate skeletal muscle wasting in septic rats by regulating hypothalamic neuropeptides.
Highlights
Melatonin (MLT) is a pineal hormone that maintains normal circardian rhythm [1]
We first demonstrated that MLT could alleviate muscle wasting and regulate certain hypothalamic neuropeptides expression in sepsis animal models
By knockdown a key hypothalamic neuropeptide, POMC, we found that MLT’s capacity of alleviating muscle wasting was weakened. These results indicated that MLT could alleviate muscle wasting by regulating the expression of POMC
Summary
Melatonin (MLT) is a pineal hormone that maintains normal circardian rhythm [1]. MLT and its metabolites modulate a variety of molecular signaling pathways including proliferation, apoptosis, metastasis, inflammation and so on [2–4].Jianfeng Duan and Minhua Cheng have contributed to this work and are listed as co-first authors.Recent studies have shown that MLT may be useful in the treatment of sepsis and septic injury due to its antioxidative and anti-inflammatory actions [5]. Melatonin (MLT) is a pineal hormone that maintains normal circardian rhythm [1]. MLT and its metabolites modulate a variety of molecular signaling pathways including proliferation, apoptosis, metastasis, inflammation and so on [2–4]. Jianfeng Duan and Minhua Cheng have contributed to this work and are listed as co-first authors. Recent studies have shown that MLT may be useful in the treatment of sepsis and septic injury due to its antioxidative and anti-inflammatory actions [5]. Further research suggested that MLT blocked NF-κB signaling induced by LPS through inhibiting the nuclear translocation and DNAbinding activity of the NF-κB p50 subunit [6]. These results indicate a promising therapeutic application for MLT in the treatment of sepsis
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