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Cited by 82Liver Disease Diagnosis and TreatmentNutrition and Health in AgingMuscle Physiology and Disorders

Myosteatosis rather than sarcopenia associates with non‐alcoholic steatohepatitis in non‐alcoholic fatty liver disease preclinical models

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Nachit, Maxime, De Rudder, Maxime, Thissen, Jean‐Paul, Schakman, Olivier, Bouzin, Caroline, Horsmans, Yves, Vande Velde, Greetje, Leclercq, Isabelle Anne·2021·Journal of Cachexia, Sarcopenia and Muscle
DOI 10.1002/jcsm.12646PMC PMC7890270
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Abstract

Background: Non‐alcoholic fatty liver (NAFL) disease (NAFLD) is the most common chronic liver disease in the world. While most subjects have ‘inert’ NAFL, a subset will progress to non‐alcoholic steatohepatitis (NASH) and its life‐threatening complications. A substantial body of literature supports that a low muscle mass, low strength, and/or muscle fatty infiltration (myosteatosis) are associated with NAFLD severity. Here, we evaluated the muscle compartment in NASH preclinical models to decipher the kinetics of muscle alterations in relation with liver disease progression. Methods: We developed and validated a micro‐computed tomography‐based methodology to prospectively study skeletal muscle mass and density in muscle and liver (i.e. reflecting fatty infiltration) in a high‐throughput and non‐invasive manner in three preclinical NAFLD/NASH rodent models: fat aussie (FOZ) mice fed a high‐fat diet (FOZ HF), wild‐type (WT) mice fed a high‐fat high‐fructose diet (WT HFF), and WT mice fed a high‐fat diet (WT HF). We compared them with WT mice fed a normal diet (WT ND) used as controls. Results: ‐FOZ HF with fibrosing NASH had sarcopenia characterized by a reduced muscle strength when compared with WT HF and WT HFF with early NASH and WT ND controls (165.2 ± 5.2 g vs. 237.4 ± 11.7 g, 256 ± 5.7 g, and 242.9 ± 9.3 g, respectively, P 60; 0.001). Muscle mass or strength was not lower in FOZ HF, WT HF, and WT HFF with early NASH than in controls. Myosteatosis was present in FOZ HF with fibrosing NASH, but also in FOZ HF, WT HF, and WT HFF with early NASH (muscle density = 0.50 ± 0.02, 0.62 ± 0.02, 0.70 ± 0.05, and 0.75 ± 0.03, respectively, with P 60; 0.001 when compared with respective controls). Myosteatosis degree was strongly correlated with NAFLD activity score ( r = −0.87, n = 67, P 60; 0.001). In multivariate analysis, the association between myosteatosis and NASH was independent from homeostatic model assessment of insulin resistance and visceral fat area ( P 60; 0.05). Myosteatosis degree powerfully discriminated NASH from benign NAFL and normal liver (area under the receiver operating characteristic = 0.96, n = 67, P 60; 0.001). Conclusions: Taken together, our data support that there is no sarcopenia in obese mice with early NASH. In contrast, the severity of myosteatosis reflects on hepatocellular damage and inflammation during early NASH development. This observation prompts us to exploit myosteatosis as a novel non‐invasive marker of NASH.

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  • Skeletal muscle fat infiltration appears to be independent of muscle mass, suggesting it precedes muscle atrophy to cause sarcopenia.

    “Skeletal muscle fat infiltration appears to be independent of muscle mass, however, suggesting it precedes muscle atrophy to cause sarcopenia.[ 37 ]”

    From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [37]

  • Skeletal muscle ectopic fat infiltration, or myosteatosis, is an abnormal phenomenon that increases with ageing and is recognized to negatively correlate with muscle mass, strength, mobility and normal metabolism.

    “Skeletal muscle ectopic fat infiltration, or myosteatosis, is an abnormal phenomenon that increases with ageing and is recognized to negatively correlate with muscle mass, strength, mobility and normal metabolism.[ 37 ]”

    From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [37]

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Authors
Nachit, M., De Rudder, M., Thissen, J., Schakman, O., Bouzin, C., Horsmans, Y., Vande Velde, G., & Leclercq, I. A.
Affiliations
  • UCLouvain (BE)
  • Laboratory of Hepato‐Gastroenterology, Institute of Experimental and Clinical Research UCLouvain Brussels Belgium
  • Cliniques Universitaires Saint-Luc (BE)
  • Department of Imaging and Pathology KU Leuven Leuven Belgium
Corresponding author
Leclercq, Isabelle Anne
ORCID
Venue
Journal of Cachexia, Sarcopenia and Muscle
Publisher
Wiley
Published
2020-11-26
Volume
12
Issue
1
Pages
144-158
ISSN
  • 2190-5991 (ISSN-L)
  • 2190-6009
DOI
10.1002/jcsm.12646
PMC
PMC7890270
OpenAlex
W3106633636
Cited by
82
References
52
Citations by year
2026: 11 · 2025: 11 · 2024: 22 · 2023: 14 · 2022: 20 · 2021: 4
FWCI
6.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, cc-by)
  • DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
  • Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (31618719)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, myosteatosis, sarcopenia, muscle mass, muscle strength, micro-computed tomography, high-fat high-fructose diet, liver fibrosis, NAFLD activity score, rodent models, liver disease progression
MeSH terms
Animals, Mice, X-Ray Microtomography, Sarcopenia, Diet, High-Fat, Non-alcoholic Fatty Liver Disease

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