Plasma high-resolution metabolomics identifies linoleic acid and linked metabolic pathways associated with bone mineral density

• Type of Material: Article
• Authors: Moriah P. Bellissimo, Emory University; Thomas Ziegler, Emory University; Dean Jones, Emory University; Ken Liu, Emory University; Jolyn Fernandes, University of Oklahoma; Joseph L. Roberts, Emory University; M. Neale Weitzmann, Emory University; Roberto Pacifici, Emory University; Jessica Alvarez, Emory University
• Language: English
• Date: 2021-02-01
• Publisher: Churchill Livingstone
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.clnu.2020.05.041
• Title of Journal or Parent Work: Clinical Nutrition
• Volume: 40
• Issue: 2
• Start Page: 467
• End Page: 475
• Grant/Funding Information: Additional grant support included NIH K01 DK102851 (JAA), R03 DK117246 (JAA), U54 AG062334 (JAA, MNW), K24 DK096574 (TRZ), P30 ES019776 (Health and Exposome Research Center at Emory; DPJ, TRZ), R01 DK112946 (RP), R01 DK108842 (RP), S10 RR028009 (RP), R01 AR068157 (MNW), and R01 AR070091 (MNW).; This work is based on information from the Emory Predictive Health Institute and Center for Health Discovery and Well Being Database supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1 TR002378.; MNW was also supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105).
• Keywords: Polyunsaturated fatty acids; Diet; PUFA; Inflammation; Life Sciences & Biomedicine; Nutrition; Activation; Omega-6; Science & Technology; Nutrition & Dietetics; Intestinal Microbiota; Fractures; Fats; Skeletal health; Patterns; R Package; Adults; Mass spectrometry; Predictive health
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health; Health Sciences, Nutrition

Abstract

Background & Aims There is a considerable degree of variation in bone mineral density (BMD) within populations. Use of plasma metabolomics may provide insight into established and novel determinants of BMD variance, such as nutrition and gut microbiome composition, to inform future prevention and treatment strategies for loss of BMD. Using high-resolution metabolomics (HRM), we examined low-molecular weight plasma metabolites and nutrition-related metabolic pathways associated with BMD. Methods This cross-sectional study included 179 adults (mean age 49.5 ± 10.3 yr, 64% female). Fasting plasma was analyzed using ultra-high-resolution mass spectrometry with liquid chromatography. Whole body and spine BMD were assessed by dual energy x-ray absorptiometry and expressed as BMD (g/cm2) or Z-scores. Multiple linear regression, pathway enrichment, and module analyses were used to determine key plasma metabolic features associated with bone density. Results Of 10,210 total detected metabolic features, whole body BMD Z-score was associated with 710 metabolites, which were significantly enriched in seven metabolic pathways, including linoleic acid, fatty acid activation and biosynthesis, and glycerophospholipid metabolism. Spine BMD was associated with 970 metabolites, significantly enriched in pro-inflammatory pathways involved in prostaglandin formation and linoleic acid metabolism. In module analyses, tryptophan- and polyamine-derived metabolites formed a network that was significantly associated with spine BMD, supporting a link with the gut microbiome. Conclusions Plasma HRM provides comprehensive information relevant to nutrition and components of the microbiome that influence bone health. This data supports pro-inflammatory fatty acids and the gut microbiome as novel regulators of postnatal bone remodeling.