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

作者：Rui Gong, Hong‐Mei Xiao, Yinhua Zhang, Qi Zhao, Kuan‐Jui Su, Lin Xu, Chenglin Mo, Qıang Zhang, Yating Du, Feng-Ye Lyu, Yuancheng Chen, Cheng Peng, Hui Li, Shidi Hu, Dao-Yan Pan, Zhi Chen, Zhang-Fang Li, Rou Zhou, Xia-Fang Wang, Jun‐Min Lu, Zeng‐Xin Ao, Yu-Qian Song, Chanyan Weng, Qing Tian, Martin R. Schiller, Christopher J. Papasian, Marco Brotto, Hui Shen, Jie Shen, Hong‐Wen Deng · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2021 · DOI：10.1210/clinem/dgab146 · 被引用次数：21 · 研究领域：Bone health and osteoporosis research、Bone Metabolism and Diseases、Metabolomics and Mass Spectrometry Studies

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 a...