Effects of short- and long-term glucocorticoid-induced osteoporosis on plasma metabolome and lipidome of ovariectomized
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(2020) 21:349
RESEARCH ARTICLE
Open Access
Effects of short- and long-term glucocorticoid-induced osteoporosis on plasma metabolome and lipidome of ovariectomized sheep Diana Cabrera1*† , Marlena Kruger2,3, Frances M. Wolber3,4,5, Nicole C. Roy1,3,6 and Karl Fraser1,3,6†
Abstract Background: Understanding the metabolic and lipidomic changes that accompany bone loss in osteoporosis might provide insights about the mechanisms behind molecular changes and facilitate developing new drugs or nutritional strategies for osteoporosis prevention. This study aimed to examine the effects of short- or long-term glucocorticoid-induced osteoporosis on plasma metabolites and lipids of ovariectomized (OVX) sheep. Methods: Twenty-eight aged ewes were divided randomly into four groups: an OVX group, OVX in combination with glucocorticoids for two months (OVXG2), and OVX in combination with five doses of glucocorticoids (OVXG5) to induce bone loss, and a control group. Liquid chromatography–mass spectrometry untargeted metabolomic analysis was applied to monthly plasma samples to follow the progression of osteoporosis over five months. Results: The metabolite profiles revealed significant differences in the plasma metabolome of OVX sheep and OVXG when compared with the control group by univariate analysis. Nine metabolites were altered, namely 5methoxytryptophan, valine, methionine, tryptophan, glutaric acid, 2-pyrrolidone-5-carboxylic acid, indole-3carboxaldehyde, 5-hydroxylysine and malic acid. Similarly, fifteen lipids were perturbed from multiple lipid classes such as lysophoslipids, phospholipids and ceramides. Conclusion: This study showed that OVX and glucocorticoid interventions altered the metabolite and lipid profiles of sheep, suggesting that amino acid and lipid metabolisms are potentially the main perturbed metabolic pathways regulating bone loss in OVX sheep. Keywords: Osteoporosis, Metabolome, Lipidome, OVX sheep
Background Osteoporosis cases are most common in the elderly population, with postmenopausal women the most affected as estrogen withdrawal induces bone loss. Currently, the diagnosis of osteoporosis is carried out by measuring bone * Correspondence: [email protected] † Diana Cabrera and Karl Fraser contributed equally to this work. 1 Food Nutrition & Health Team, AgResearch Grasslands, Tennent Drive, Palmerston North 4442, New Zealand Full list of author information is available at the end of the article
mineral density (BMD) as well as measuring bone turnover biomarkers [1–4]. While bone imaging scans are accepted as non-invasive methods, changes in BMD can only be detected by this method over a period of years [3, 4]. Thus, the development of a fast and simple prognostic method is desired, where the detection of early biomarkers for osteoporosis can be used to diagnose or predict the risk of bone loss in postmenopausal women. Metabolomics is an emerging tool for studying many diseases including cancer, diabetes, Alzheimer’s, and
© The Author(s). 2020 Open Access This article is licensed
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