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. 2020 May 12;10:138. doi: 10.1038/s41398-020-0819-5

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Pathway analysis identified the significantly altered metabolic pathways in BMAT in response to boss loss in ovariectomized (OVX) rabbits. b Fluoxetine treatment leads to the accumulation of total sphingomyelins (SMs) in BMAT of both sham and OVX rabbits. Data were mean ± sem, N = 8 rabbits/group, *P < 0.05 and **P < 0.01. c The significant decrease of total ceramides in BMAT in response to fluoxetine treatment. Data were mean ± sem, N = 8 rabbits/group, *P < 0.05. d Fluoxetine treatment significantly reduces sphingosine-1-phosphate (S1P) content in BMAT in both sham and OVX rabbits. Data were mean ± sem, N = 8 rabbits/group, *P < 0.01. e The reduction of BMD is significantly correlated with the increase of SMs and the decrease of S1P in BMAT in response to fluoxetine. N = 8/group. Spearman correlation was used, and P < 0.05. Total SMs (f), ceramides (g), and S1P (h) in BMAT of OVX-CUMS rats treated with fluoxetine or saline. Data were mean ± sem, N = 8/group and **P < 0.01. i The top 25 metabolites in BMAT correlated with BMD changes in rats. Data were log 2 transformed, and Pearson’s correlation was conducted. j Fluoxetine results in the dramatic decrease of the protein expression of SPHK1, ACER1, and ASM in the BMAT of OVX rabbits. A representative image from three independent blots was shown. GAPDH was used as the loading control. k μCT analysis of the trabecular bone region of right distal femora for ASM knockout (Smpd1^−/−) and wild-type mice (20 weeks of age). Scar bars, 350 µm. l Quantification of trabecular bone volume/tissue volume (BV/TV) in wild-type and ASM KO mice. m Trabecular number (Tb. N). n The trabecular spacing (Tb. Sp). Data were mean ± sem, N = 8 mice/group and **P < 0.01.