Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia

Obesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. He...

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Main Authors: Eun Bee Choi, Jae Hun Jeong, Hye Min Jang, Yu Jeong Ahn, Kyu Hyeon Kim, Hyeong Seok An, Jong Youl Lee, Eun Ae Jeong, Jaewoong Lee, Hyun Joo Shin, Kyung Eun Kim, Gu Seob Roh
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/5/758
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author Eun Bee Choi
Jae Hun Jeong
Hye Min Jang
Yu Jeong Ahn
Kyu Hyeon Kim
Hyeong Seok An
Jong Youl Lee
Eun Ae Jeong
Jaewoong Lee
Hyun Joo Shin
Kyung Eun Kim
Gu Seob Roh
author_facet Eun Bee Choi
Jae Hun Jeong
Hye Min Jang
Yu Jeong Ahn
Kyu Hyeon Kim
Hyeong Seok An
Jong Youl Lee
Eun Ae Jeong
Jaewoong Lee
Hyun Joo Shin
Kyung Eun Kim
Gu Seob Roh
author_sort Eun Bee Choi
collection DOAJ
description Obesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. Here, we report that elevated LCN2 levels in skeletal muscle are linked to muscle atrophy-related inflammation and oxidative stress in leptin-deficient ob/ob mice. RNA sequencing analyses indicated the <i>LCN2</i> gene expression is enhanced in skeletal muscle of ob/ob mice with sarcopenia. In addition to muscular iron accumulation in ob/ob mice, expressions of iron homeostasis-related divalent metal transporter 1, ferritin, and hepcidin proteins were increased in ob/ob mice compared to lean littermates, whereas expressions of transferrin receptor and ferroportin were reduced. Collectively, these findings demonstrate that LCN2 functions as a potent proinflammatory factor in skeletal muscle in response to obesity-related sarcopenia and is thus a therapeutic candidate target for sarcopenia treatment.
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spelling doaj.art-8a2c47e902024a9f8a96d44fdcaa7f0a2023-11-21T19:07:20ZengMDPI AGAntioxidants2076-39212021-05-0110575810.3390/antiox10050758Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with SarcopeniaEun Bee Choi0Jae Hun Jeong1Hye Min Jang2Yu Jeong Ahn3Kyu Hyeon Kim4Hyeong Seok An5Jong Youl Lee6Eun Ae Jeong7Jaewoong Lee8Hyun Joo Shin9Kyung Eun Kim10Gu Seob Roh11Department of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Medicine, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, KoreaObesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. Here, we report that elevated LCN2 levels in skeletal muscle are linked to muscle atrophy-related inflammation and oxidative stress in leptin-deficient ob/ob mice. RNA sequencing analyses indicated the <i>LCN2</i> gene expression is enhanced in skeletal muscle of ob/ob mice with sarcopenia. In addition to muscular iron accumulation in ob/ob mice, expressions of iron homeostasis-related divalent metal transporter 1, ferritin, and hepcidin proteins were increased in ob/ob mice compared to lean littermates, whereas expressions of transferrin receptor and ferroportin were reduced. Collectively, these findings demonstrate that LCN2 functions as a potent proinflammatory factor in skeletal muscle in response to obesity-related sarcopenia and is thus a therapeutic candidate target for sarcopenia treatment.https://www.mdpi.com/2076-3921/10/5/758lipocalin-2ironinflammationoxidative stresssarcopeniaob/ob mouse
spellingShingle Eun Bee Choi
Jae Hun Jeong
Hye Min Jang
Yu Jeong Ahn
Kyu Hyeon Kim
Hyeong Seok An
Jong Youl Lee
Eun Ae Jeong
Jaewoong Lee
Hyun Joo Shin
Kyung Eun Kim
Gu Seob Roh
Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia
Antioxidants
lipocalin-2
iron
inflammation
oxidative stress
sarcopenia
ob/ob mouse
title Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia
title_full Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia
title_fullStr Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia
title_full_unstemmed Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia
title_short Skeletal Lipocalin-2 Is Associated with Iron-Related Oxidative Stress in ob/ob Mice with Sarcopenia
title_sort skeletal lipocalin 2 is associated with iron related oxidative stress in ob ob mice with sarcopenia
topic lipocalin-2
iron
inflammation
oxidative stress
sarcopenia
ob/ob mouse
url https://www.mdpi.com/2076-3921/10/5/758
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