Metabolomics Coupled with Pathway Analysis Provides Insights into Sarco-Osteoporosis Metabolic Alterations and Estrogen Therapeutic Effects in Mice

Abstract

Postmenopausal osteoporosis (PMOP) and sarcopenia are common diseases that predominantly affect postmenopausal women. In the occurrence and development of these two diseases, they are potentially pathologically connected with each other at various molecular levels. However, the application of metabolomics in sarco-osteoporosis and the metabolic rewiring happening throughout the estrogen loss-replenish process have not been reported. To investigate the metabolic alteration of sarco-osteoporosis and the possible therapeutical effects of estradiol, 24 mice were randomly divided into sham surgery, ovariectomy (OVX), and estradiol-treated groups. Three-dimensional reconstructions and histopathology examination showed significant bone loss after ovariectomy. Estrogen can well protect against OVX-induced bone loss deterioration. UHPLC-Q-TOF/MS was preformed to profile semi- polar metabolites of skeletal muscle samples from all groups. Metabolomics analysis revealed metabolic rewiring occurred in OVX group, most of which can be reversed by estrogen supplementation. In total, 65 differential metabolites were identified, and pathway analysis revealed that sarco-osteoporosis was related to the alterations in purine metabolism, glycerophospholipid metabolism, arginine biosynthesis, tryptophan metabolism, histidine metabolism, oxidative phosphorylation, and thermogenesis, which provided possible explanations for the metabolic mechanism of sarco-osteoporosis. This study indicates that an UHPLC-Q-TOF/MS-based metabolomics approach can elucidate the metabolic reprogramming mechanisms of sarco-osteoporosis and provide biological evidence of the therapeutical effects of estrogen on sarco-osteoporosis.

Ovariectomy-induced hormone deprivation aggravates Aβ1-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer’s disease

“…Indeed, female sex hormone depletion was linked closely to low bone mineral density ( 94 ). Estrogen receptors can be also found in the bone, mediating protection of the bone structure, by inhibiting osteoclast activity and stimulating development of long bones and pubic epiphyses ( 94 – 96 ). The OVX-induced somatic changes presented in the literature were also supported by the somatic z-score, calculated from the body weight change, body fat ratio, and uterus weight.…”

Applications of Metabolomics in Calcium Metabolism Disorders in Humans

“…These include glycerophospholipid metabolism, tryptophan metabolism, arginine biosynthesis, histidine metabolism, purine metabolism, thermogenesis and oxidative phosphorylation. With this study, the authors provided new insights into the possible therapeutic effects of estrogens on sarco-osteoporosis [ 74 ]. A recent non-targeted metabolomics study presented relationships between kidney, bone and bone marrow of ovariectomized rats with postmenopausal osteoporosis.…”

MALDI-TOF MS: application in diagnosis, dereplication, biomolecule profiling and microbial ecology

“…For the characterization of large biomolecules, the fluid is generally diluted in different ratios while mixing with the matrix (Yamazaki et al 2020 ; Anderson et al 2012 ). Biomolecule profiling gives an insight into physiological, developmental, and pathological changes in the body (Wei et al 2021 ). Principal component analysis (PCA) is usually involved in identifying differences in the patterns of biomolecules between samples.…”