Metabolomics coupled with pathway analysis provides insights into sarco-osteoporosis metabolic alterations and estrogen therapeutic effects in mice

Ziheng Wei, Fei Ge, Yanting Che, Si Wu, Xin Dong, Dianwen Song

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Article number41
JournalBiomolecules
Volume12
Issue number1
DOIs
StatePublished - 1 Jan 2022
Externally publishedYes

Keywords

  • Estrogen
  • Metabolomics
  • Postmenopausal osteoporosis
  • Sarcopenia
  • Skeletal muscles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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