Abstract
Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether
estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study
was designed to test the effect of estrogen on muscle wasting and its relationship
with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3
groups: control group, sepsis group, and estrogen treated sepsis group. Animals were
intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed
by subcutaneous injection of 17β-estradiol (1 mg/kg) or saline. Twenty-four hours
later, all animals were killed and their hypothalamus and skeletal muscles were harvested
for analysis. Muscle wasting markers, hypothalamic neuropeptides, and hypothalamic
inflammatory markers were measured. As a result, lipopolysaccharide administration
caused a significant increase in muscle wasting, hypothalamic inflammation, and anorexigenic
neuropeptides (POMC and CART) gene expression, and a significant decrease in orexigenic
neuropeptides (AgRP and NPY) gene expression. Administration of estrogen signifcantl
attenuated lipopolysaccharide-induced muscle wasting (body weight and extensor digitorum
longus loss [52 and 62 %], tyrosine and 3-methylhistidine release [17 and 22 %], muscle
ring fnger 1 [MuRF-1; 65 %], and muscle atrophy F-box [MAFbx] gene expression), hypothalamic
inflammation (Tumor necrosis factor-α and interlukin-1β [69 and 70%]) as well as alteration
of POMC, CART and AgRP (61, 37, and 1008 %) expression.In conclusion, estrogen could
alleviate sepsis-induced muscle wasting and it was associated with reducing hypothalamic
inflammation and alteration of hypothalamic neuropeptides.
Key words
estrogen - muscle wasting - sepsis - hypothalamic neuropeptides - central inflammation
