Fatty acid amides as potential circulating biomarkers for sarcopenia

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 bi...

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Main Authors: Ye An Kim, Seung Hun Lee, Jung‐Min Koh, Seung‐hyun Kwon, Young Lee, Han Jin Cho, Hanjun Kim, Su Jung Kim, Ji Hyun Lee, Hyun Ju Yoo, Je Hyun Seo
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:Journal of Cachexia, Sarcopenia and Muscle
Subjects:
Online Access:https://doi.org/10.1002/jcsm.13244
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author Ye An Kim
Seung Hun Lee
Jung‐Min Koh
Seung‐hyun Kwon
Young Lee
Han Jin Cho
Hanjun Kim
Su Jung Kim
Ji Hyun Lee
Hyun Ju Yoo
Je Hyun Seo
author_facet Ye An Kim
Seung Hun Lee
Jung‐Min Koh
Seung‐hyun Kwon
Young Lee
Han Jin Cho
Hanjun Kim
Su Jung Kim
Ji Hyun Lee
Hyun Ju Yoo
Je Hyun Seo
author_sort Ye An Kim
collection DOAJ
description 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.
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spelling doaj.art-7284666b74344d32af986989d0ddece72023-06-02T06:44:01ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092023-06-011431558156810.1002/jcsm.13244Fatty acid amides as potential circulating biomarkers for sarcopeniaYe An Kim0Seung Hun Lee1Jung‐Min Koh2Seung‐hyun Kwon3Young Lee4Han Jin Cho5Hanjun Kim6Su Jung Kim7Ji Hyun Lee8Hyun Ju Yoo9Je Hyun Seo10Division of Endocrinology, Department of Internal Medicine Veterans Health Service Medical Center Seoul South KoreaDivision of Endocrinology and Metabolism, Asan Medical Center University of Ulsan College of Medicine Seoul South KoreaDivision of Endocrinology and Metabolism, Asan Medical Center University of Ulsan College of Medicine Seoul South KoreaVeterans Medical Research Institute Veterans Health Service Medical Center Seoul South KoreaVeterans Medical Research Institute Veterans Health Service Medical Center Seoul South KoreaBiomedical Research Center, Asan Institute for Life Sciences Asan Medical Center Seoul South KoreaBiomedical Research Center, Asan Institute for Life Sciences Asan Medical Center Seoul South KoreaDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul South KoreaDivision of Endocrinology, Department of Internal Medicine Veterans Health Service Medical Center Seoul South KoreaDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul South KoreaVeterans Medical Research Institute Veterans Health Service Medical Center Seoul South KoreaAbstract 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.https://doi.org/10.1002/jcsm.13244AgingMetabolomicsSarcopeniaBiomarkersFatty acid amides
spellingShingle Ye An Kim
Seung Hun Lee
Jung‐Min Koh
Seung‐hyun Kwon
Young Lee
Han Jin Cho
Hanjun Kim
Su Jung Kim
Ji Hyun Lee
Hyun Ju Yoo
Je Hyun Seo
Fatty acid amides as potential circulating biomarkers for sarcopenia
Journal of Cachexia, Sarcopenia and Muscle
Aging
Metabolomics
Sarcopenia
Biomarkers
Fatty acid amides
title Fatty acid amides as potential circulating biomarkers for sarcopenia
title_full Fatty acid amides as potential circulating biomarkers for sarcopenia
title_fullStr Fatty acid amides as potential circulating biomarkers for sarcopenia
title_full_unstemmed Fatty acid amides as potential circulating biomarkers for sarcopenia
title_short Fatty acid amides as potential circulating biomarkers for sarcopenia
title_sort fatty acid amides as potential circulating biomarkers for sarcopenia
topic Aging
Metabolomics
Sarcopenia
Biomarkers
Fatty acid amides
url https://doi.org/10.1002/jcsm.13244
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