Observational Study
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World J Gastroenterol. Feb 21, 2025; 31(7): 100039
Published online Feb 21, 2025. doi: 10.3748/wjg.v31.i7.100039
Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study
Yolanda Real Martinez, Carlos Ernesto Fernandez-Garcia, Esther Fuertes-Yebra, Mario Calvo Soto, Angela Berlana, Vicente Barrios, Maria Caldas, Leticia Gonzalez Moreno, Luisa Garcia-Buey, Begoña Molina Baena, Miguel Sampedro-Nuñez, Maria J Beceiro, C García-Monzón, Águeda González-Rodríguez
Yolanda Real Martinez, Mario Calvo Soto, Maria Caldas, Leticia Gonzalez Moreno, Luisa Garcia-Buey, Maria J Beceiro, Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
Carlos Ernesto Fernandez-Garcia, Esther Fuertes-Yebra, Angela Berlana, C García-Monzón, Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
Vicente Barrios, Department of Endocrinology, Department of Pediatrics, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid 28009, Spain
Vicente Barrios, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid 28029, Spain
Begoña Molina Baena, Miguel Sampedro-Nuñez, Servicio de Endocrinología y Nutrición, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
Águeda González-Rodríguez, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, Madrid 28029, Spain
Águeda González-Rodríguez, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Madrid 28029, Spain
Co-corresponding authors: Yolanda Real Martinez and Águeda González-Rodríguez.
Author contributions: González-Rodríguez A and Real Martinez Y contributed to the conceptualization and project administration; Fernandez-Garcia CE and Barrios V contributed to the methodology; Fernandez-Garcia CE, Fuertes-Yebra E, Calvo Soto M, Berlana A, Barrios V, Caldas M, Gonzalez Moreno L, Molina Baena B, and Sampedro-Nuñez M contributed to the data curation; Fernandez-Garcia CE contributed to the formal analysis; Fernandez-Garcia CE, Fuertes-Yebra E, Real Martinez Y, Calvo Soto M, Berlana A, Barrios V, Caldas M, Gonzalez Moreno L, Molina Baena B, Garcia-Buey L, Beceiro MJ, and Sampedro-Nuñez M contributed to the investigation; González-Rodríguez A and García-Monzón C contributed to the resources; Real Martinez Y, Fernandez-Garcia CE, González-Rodríguez A, and García-Monzón C contributed to writing the original draft preparation; Fernandez-Garcia CE, Calvo Soto M, Barrios V, Caldas M, Gonzalez Moreno L, Garcia-Buey L, Molina Baena B, Sampedro-Nuñez M, and García-Monzón C contributed to writing review and editing; Real Martinez Y, Fernandez-Garcia CE, and García-Monzón C contributed to visualization; Real Martinez Y, González-Rodríguez A, and García-Monzón C contributed to the supervision; Real Martinez Y contributed to funding acquisition; All authors have read and agreed to the published version of the manuscript.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of La Princesa University Hospital (No. RRN 4645, October 21, 2021).
Informed consent statement: Informed consent was obtained from all subjects involved in the study.
Conflict-of-interest statement: This research was funded by Persan Farma Laboratoires. Also, this work was supported by contract CP19/00032 from Instituto de Salud Carlos III (ISCIII, Spain) and Fondo Europeo para el Desarrollo Regional (FEDER), and CIBERDEM (ISCIII) to AGR. CEFG was supported by a Sara-Borrell postdoctoral contract (CD20/00199) from ISCIII/FEDER (Spain). AB was supported by a research contract (PEJ-2020-AI/BMD-18301) funded by Comunidad de Madrid (Spain).
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at yrealm@gmail.com. Participants gave informed consent for data sharing.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yolanda Real Martinez, PhD, Attending Doctor, Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Diego de Leon 62, Madrid 28006, Spain. yrealm@gmail.com
Received: August 5, 2024
Revised: December 4, 2024
Accepted: December 25, 2024
Published online: February 21, 2025
Processing time: 167 Days and 8.8 Hours
Abstract
BACKGROUND

Skeletal muscle alterations (SMAs) are being increasingly recognized in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and appear to be associated with deleterious outcomes in these patients. However, their actual prevalence and pathophysiology remain to be elucidated.

AIM

To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.

METHODS

Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria, recruited from the outpatient clinics of a tertiary level hospital. The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography. Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort. Statistical analysis was performed comparing results according to liver fibrosis and steatosis.

RESULTS

No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis. Interestingly, serum levels of fibroblast growth factor-21 (FGF21) were significantly higher in patients with MASLD with advanced hepatic fibrosis (F3-F4) than in those with lower fibrosis stages (F0-F2) (197.49 ± 198.27 pg/mL vs 95.62 ± 83.67 pg/mL; P = 0.049). In addition, patients with MASLD with severe hepatosteatosis (S3) exhibited significantly higher serum levels of irisin (1116.87 ± 1161.86 pg/mL) than those with lower grades (S1-S2) (385.21 ± 375.98 pg/mL; P = 0.001).

CONCLUSION

SMAs were uncommon in the patients with MASLD studied. Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis, respectively, with potential implications as biomarkers.

Keywords: Skeletal muscle alterations; Myokines; Metabolic dysfunction-associated steatotic liver disease; Liver fibrosis; Hepatosteatosis

Core Tip: Skeletal muscle alterations (SMAs) share pathophysiology mechanisms with metabolic dysfunction-associated steatotic liver disease (MASLD), in which inflammation, insulin resistance, and physical inactivity are key factors. Previous studies describe these alterations, especially reduced muscle function, in patients with a higher degree of liver fibrosis and steatosis. We determined the prevalence of SMAs in patients diagnosed with MASLD in an outpatient setting in Spain, and analyzed the myokines as potential biomarkers of inflammation. We did not find significant SMAs, but found a marked increase in serum levels of irisin and fibroblast growth factor 21 in advanced disease stages, which deserves further assessment.