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Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women

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Abstract

Background

Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women’s health.

Purpose

To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women.

Methods and results

Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk.

Conclusions

Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

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Data availability

Some or all datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This study was supported by grants from the National Research Foundation of Korea (NRF) funded by the South Korean government (MSIT) [grant number: 2021R1C1C2006842] and from the Asan Institute for Life Science, Asan Medical Center, Seoul, South Korea [grant number: 2022IP0036].

Author information

Author notes

  1. S. J. Kim, Y. Jo and S. J. Park contributed equally to this work.

Authors and Affiliations

  1. Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center,, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea

    S. J. Kim & H. J. Yoo

  2. Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, South Korea

    Y. Jo & D. Ryu

  3. Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea

    S. J. Park, E. Ji, J. Y. Lee, E. Choi & K. Kim

  4. Division of Geriatrics, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea

    J.-Y. Baek, I. Y. Jang & H.-W. Jung

  5. Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea

    K. Kim

  6. Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea

    B.-J. Kim

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  1. S. J. Kim
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Correspondence to D. Ryu, H. J. Yoo or B.-J. Kim.

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The present study received the approval of the AMC Institutional Review Board (no. 2020–0259).

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Kim, S.J., Jo, Y., Park, S.J. et al. Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02338-x

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