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Constant light exposure aggravates POMC-mediated muscle wasting associated with hypothalamic alteration of circadian clock and SIRT1 in endotoxemia rats.

Authors :
Chen, Yan
Cheng, Minhua
Su, Ting
Gao, Tao
Yu, Wenkui
Source :
Biochemical & Biophysical Research Communications. Jan2019, Vol. 508 Issue 3, p811-817. 7p.
Publication Year :
2019

Abstract

Abstract Constant light exposure is widespread in the intensive care unit (ICU) and could increase the rate of brain dysfunction as delirium and sleep disorders in critical patients. And the activation of hypothalamic neuropeptides is proved to play a crucial role in regulating hypercatabolism, especially skeletal muscle wasting in critical patients, which could lead to serious complications and poor prognosis. Here we investigated the hypothesis that constant light exposure could aggravate skeletal muscle wasting in endotoxemia rats and whether it was associated with alterations of circadian clock and hypothalamic proopiomelanocortin(POMC) expression. Fifty-four adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide(LPS) or saline, subjected to constant light or a 12:12 h light-dark cycle for 7 days. On day 8, rats were sacrificed across six time points in 24 h and hypothalamus tissues and skeletal muscle were obtained. Rates of muscle wasting were measured by 3-methylhistidine(3-MH) and tyrosine release as well as expression of two muscle atrophic genes, muscle ring finger 1(MuRF-1) and muscle atrophy F-box(MAFbx). The expression of circadian clock genes, silent information regulator 1(SIRT1), POMC and hypothalamic inflammatory cytokines were also detected. Results showed that LPS administration significantly increased hypothalamic POMC expression, inflammatory cytokine levels and muscle wasting rates. Meanwhile constant light exposure disrupted the circadian rhythm, declined the expression of SIRT1 as well as aggravated hypothalamic POMC overexpression and skeletal muscle wasting in rats with endotoxemia. Taken together, the results demonstrated that constant light exposure could aggravate POMC-mediated skeletal muscle wasting in endotoxemia rats, which is associated with alteration of circadian clocks and SIRT1 in the hypothalamus. Highlights • Endotoxemia increases POMC expression and results in skeletal muscle wasting. • Constant light exposure aggravates muscle wasting and POMC activation in endotoxemia. • Constant light exposure disrupts circadian rhythm and decreases the expression of SIRT1 in the hypothalamus. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0006291X
Volume :
508
Issue :
3
Database :
Academic Search Index
Journal :
Biochemical & Biophysical Research Communications
Publication Type :
Academic Journal
Accession number :
133735971
Full Text :
https://doi.org/10.1016/j.bbrc.2018.12.020