Deterioration of mitochondrial function in the human intercostal muscles differs among individuals with sarcopenia, obesity, and sarcopenic obesity.


Journal

Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603

Informations de publication

Date de publication:
05 2021
Historique:
received: 07 09 2020
revised: 19 02 2021
accepted: 05 03 2021
pubmed: 3 5 2021
medline: 3 9 2021
entrez: 2 5 2021
Statut: ppublish

Résumé

Sarcopenic obesity (SO) increases the risk of mortality more than sarcopenia or obesity alone. Sarcopenia weakens the peripheral and respiratory muscles, leading to respiratory complications. It also induces mitochondrial dysfunction in the peripheral muscle; however, whether mitochondrial dysfunction in respiratory muscles differs among individuals with obesity, sarcopenia, and SO remains unknown. We evaluated the deterioration of respiratory muscle strength and mitochondrial function among normal, sarcopenia, obesity, and SO subjects. Twenty-five patients who underwent lung resections were enrolled between April 2017 and January 2021, and their intercostal muscles were harvested. Based on their L3 muscle index and visceral fat area, the patients were divided into four groups (normal, obesity, sarcopenia, and SO). The clinical data, mRNA expression, and protein expressions associated with mitochondrial biogenesis/fusion/fission in the intercostal muscles were compared among the four groups. The respiratory muscle strength was evaluated using peak expiratory flow rate (PEFR). The PEFR values of the four groups were not significantly different. The levels of pAkt/Akt and mTOR (a marker of protein synthesis) were not significantly different among the four groups; however, those in the SO group were substantially lower than those in the sarcopenia or obesity groups. The levels of Atrogen-1 and MuRF1 (a marker of protein degradation) were not significantly different among the four groups; however, those in the SO group were substantially higher than those in the sarcopenia or obesity groups. Expression of PGC1-α (a marker of mitochondrial biogenesis) in the SO group was significantly lower than that in the normal group. MFN1 and MFN2 (marker of mitochondrial fusion) levels were significantly lower in the SO group than those in the normal group. DRP1 (a marker of mitochondrial fission) level in the SO group was substantially lower than that in the normal group. The expression of TNF-α (a pro-inflammatory cytokine) in the SO group was substantially lower than that in the normal group. Our results suggest that the deterioration of protein synthesis and degradation of mitochondrial function in the respiratory muscles was most prominent in the SO before the weakening of the respiratory muscles. The deterioration mechanism may differentially regulate obesity, sarcopenia, and SO.

Sections du résumé

BACKGROUND & AIMS
Sarcopenic obesity (SO) increases the risk of mortality more than sarcopenia or obesity alone. Sarcopenia weakens the peripheral and respiratory muscles, leading to respiratory complications. It also induces mitochondrial dysfunction in the peripheral muscle; however, whether mitochondrial dysfunction in respiratory muscles differs among individuals with obesity, sarcopenia, and SO remains unknown. We evaluated the deterioration of respiratory muscle strength and mitochondrial function among normal, sarcopenia, obesity, and SO subjects.
METHODS
Twenty-five patients who underwent lung resections were enrolled between April 2017 and January 2021, and their intercostal muscles were harvested. Based on their L3 muscle index and visceral fat area, the patients were divided into four groups (normal, obesity, sarcopenia, and SO). The clinical data, mRNA expression, and protein expressions associated with mitochondrial biogenesis/fusion/fission in the intercostal muscles were compared among the four groups.
RESULTS
The respiratory muscle strength was evaluated using peak expiratory flow rate (PEFR). The PEFR values of the four groups were not significantly different. The levels of pAkt/Akt and mTOR (a marker of protein synthesis) were not significantly different among the four groups; however, those in the SO group were substantially lower than those in the sarcopenia or obesity groups. The levels of Atrogen-1 and MuRF1 (a marker of protein degradation) were not significantly different among the four groups; however, those in the SO group were substantially higher than those in the sarcopenia or obesity groups. Expression of PGC1-α (a marker of mitochondrial biogenesis) in the SO group was significantly lower than that in the normal group. MFN1 and MFN2 (marker of mitochondrial fusion) levels were significantly lower in the SO group than those in the normal group. DRP1 (a marker of mitochondrial fission) level in the SO group was substantially lower than that in the normal group. The expression of TNF-α (a pro-inflammatory cytokine) in the SO group was substantially lower than that in the normal group.
CONCLUSION
Our results suggest that the deterioration of protein synthesis and degradation of mitochondrial function in the respiratory muscles was most prominent in the SO before the weakening of the respiratory muscles. The deterioration mechanism may differentially regulate obesity, sarcopenia, and SO.

Identifiants

pubmed: 33933735
pii: S0261-5614(21)00148-5
doi: 10.1016/j.clnu.2021.03.009
pii:
doi:

Substances chimiques

Cytokines 0
RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2697-2706

Informations de copyright

Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no conflict of interest.

Auteurs

Kun Woo Kim (KW)

Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon 21565, South Korea.

Mi-Ock Baek (MO)

Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 21999, South Korea; Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, South Korea; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, South Korea.

Mee-Sup Yoon (MS)

Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 21999, South Korea; Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, South Korea; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, South Korea. Electronic address: msyoon@gachon.ac.kr.

Kuk Hui Son (KH)

Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon 21565, South Korea. Electronic address: dr632@gilhospital.com.

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Classifications MeSH