한빛사논문
- 조회578
Ye An Kim 1#, Seung Hun Lee 2#, Jung-Min Koh 2, Seung-Hyun Kwon 3, Young Lee 3, Han Jin Cho 4, Hanjun Kim 4, Su Jung Kim 5, Ji Hyun Lee 1, Hyun Ju Yoo 5*, Je Hyun Seo 3*
1Division of Endocrinology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, South Korea.
2Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
3Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, South Korea.
4Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
5Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
#These authors contributed equally to this work.
*CORRESPONDING AUTHORS : Hyun Ju Yoo, Je Hyun Seo
Abstract
Background: Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics.
Methods: Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated.
Results: Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/μL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532-0.698). DHA EA level ≤ 4.60 fmol/μL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03-4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (P = 0.0497).
Conclusions: Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become a reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the metabolomic changes relevant to sarcopenia from an aging perspective.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-05-19)
- 국내 연구진
- 의약학 > 응용의학
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