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

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

doi:10.3390/biom12010041

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.

Highlights

Introduction iationsBone and muscle loss alone with aging is considered as a huge threat to loss of independence in later life [1]
Our results demonstrate the differential metabolites and provide a preliminary molecular explanation based on pathway analysis (Figure 1)
A decline in estrogen level in menopausal women is assumed to be associated with sarcopenia and frailty, it has been suggested that estrogen regulates muscle mass and function [16,17]

Summary

Introduction

Introduction iationsBone and muscle loss alone with aging is considered as a huge threat to loss of independence in later life [1]. Postmenopausal osteoporosis (PMOP) and sarcopenia are common diseases tending to occur simultaneously in elderly people, especially in postmenopausal women [2,3]. They are both associated with significant morbidity and lead to considerable health and social costs [4,5]. PMOP, one of the most concerned health public issues, is characterized by bone loss and microarchitectural deterioration, leaving patients with much higher risk of fractures [6]. The medical cost of osteoporotic fracture in China is expected to increase to 264.7 billion US dollars in 2050 [10]

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