Abstract
BackgroundUnderstanding 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.MethodsTwenty-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.ResultsThe 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 5-methoxytryptophan, valine, methionine, tryptophan, glutaric acid, 2-pyrrolidone-5-carboxylic acid, indole-3-carboxaldehyde, 5-hydroxylysine and malic acid. Similarly, fifteen lipids were perturbed from multiple lipid classes such as lysophoslipids, phospholipids and ceramides.ConclusionThis 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.
Highlights
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
Changes in the plasma metabolites of the OVX group were observed with a decrease in the relative intensities of all the metabolites one month after OVX when compared with baseline, with the exception of 5methoxytryptophan, methionine and tryptophan
At month one, all metabolites significantly increased in relative intensity in the OVXG group when compared with baseline, while comparing OVXG vs OVX, the fold changes (FC) of all the metabolites were significantly greater than 1 at month one, while at month two only the fold change of methionine was greater than 2
Summary
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. Lipid accumulation alters bone marrow cells and could be a determinant of increased bone remodelling that may affect bone mass, and has been associated with obesity and osteoporosis in postmenopausal women [14, 15]. Lipids and their derivatives, such as sphingosine-1-phosphate, lysophosphatidic acid and some fatty acid amides, are known to regulate cellular process, and any change in these can lead to bone pathologies such as osteoporosis [16]. The clinical symptoms in these rodent models are poorly representative of the naturally occurring postmenopausal condition in humans [24]
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