Title

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women

Authors

Rui Gong, The Third Affiliated Hospital of Southern Medical University
Hong Mei Xiao, School of Basic Medical Science Central South University
Yin Hua Zhang, The Third Affiliated Hospital of Southern Medical University
Qi Zhao, University of Tennessee Health Science Center
Kuan Jui Su, Tulane University
Xu Lin, The Third Affiliated Hospital of Southern Medical University
Cheng Lin Mo, The University of Texas at Arlington
Qiang Zhang, Tulane University
Ya Ting Du, The University of Texas at Arlington
Feng Ye Lyu, LC-Bio Technologies (Hangzhou) CO.LTD
Yuan Cheng Chen, The Third Affiliated Hospital of Southern Medical University
Cheng Peng, The Third Affiliated Hospital of Southern Medical University
Hui Min Liu, School of Basic Medical Science Central South University
Shi Di Hu, The Third Affiliated Hospital of Southern Medical University
Dao Yan Pan, The Third Affiliated Hospital of Southern Medical University
Zhi Chen, The Third Affiliated Hospital of Southern Medical University
Zhang Fang Li, The Third Affiliated Hospital of Southern Medical University
Rou Zhou, The Third Affiliated Hospital of Southern Medical University
Xia Fang Wang, The Third Affiliated Hospital of Southern Medical University
Jun Min Lu, The Third Affiliated Hospital of Southern Medical University
Zeng Xin Ao, The Third Affiliated Hospital of Southern Medical University
Yu Qian Song, The Third Affiliated Hospital of Southern Medical University
Chan Yan Weng, The Third Affiliated Hospital of Southern Medical University
Qing Tian, Tulane University
Martin R. Schiller, University of Nevada, Las VegasFollow
Christopher J. Papasian, University of Missouri, Kansas City
Marco Brotto, The University of Texas, Arlington
Hui Shen, Tulane University
Jie Shen, The Third Affiliated Hospital of Southern Medical University
Hong-Wen Deng, Tulane University

Document Type

Article

Publication Date

3-8-2021

Publication Title

Journal of Clinical Endocrinology and Metabolism

Volume

106

Issue

8

First page number:

E3159

Last page number:

E3177

Abstract

Context: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. Design and Methods: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM). Conclusions: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

Keywords

Bone mineral density; Fatty acids; Metabolites; Metabolomics; Postmenopausal osteoporosis; Whole-genome sequencing

Disciplines

Endocrinology, Diabetes, and Metabolism | Medical Specialties | Medicine and Health Sciences | Public Health | Women's Health

Language

English

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