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Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease - PubMed

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Review

Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease

Guillaume Henin et al. JHEP Rep. 2023.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of multisystemic complications, including muscle changes such as sarcopenia and myosteatosis that can reciprocally affect liver function. We conducted a systematic review to highlight innovative assessment tools, pathophysiological mechanisms and metabolic consequences related to myosteatosis in MASLD, based on original articles screened from PUBMED, EMBASE and COCHRANE databases. Forty-six original manuscripts (14 pre-clinical and 32 clinical studies) were included. Microscopy (8/14) and tissue lipid extraction (8/14) are the two main assessment techniques used to measure muscle lipid content in pre-clinical studies. In clinical studies, imaging is the most used assessment tool and included CT (14/32), MRI (12/32) and ultrasound (4/32). Assessed muscles varied across studies but mainly included paravertebral (4/14 in pre-clinical; 13/32 in clinical studies) and lower limb muscles (10/14 in preclinical; 13/32 in clinical studies). Myosteatosis is already highly prevalent in non-cirrhotic stages of MASLD and correlates with disease activity when using muscle density assessed by CT. Numerous pathophysiological mechanisms were found and included: high-fat and high-fructose diet, dysregulation in fatty acid transport and ketogenesis, endocrine disorders and impaired microRNA122 pathway signalling. In this review we also uncover several potential consequences of myosteatosis in MASLD, such as insulin resistance, MASLD progression from steatosis to metabolic steatohepatitis and loss of muscle strength. In conclusion, data on myosteatosis in MASLD are already available. Screening for myosteatosis could be highly relevant in the context of MASLD, considering its correlation with MASLD activity as well as its related consequences.

Keywords: MASH; MASLD; adipokines; hepatokines; inflammation; insulin resistance; liver; metabolic dysfunction-associated steatohepatitis; metabolic dysfunction-associated steatotic liver disease; muscle; myokines; myosteatosis.

© 2023 The Author(s).

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Conflict of interest statement

GH received a travel grant from Gilead Sciences. IAL has patents planned, issued, or pending (PCT/EP2022/065769 Ref WO/2022/258788); received research grants from FNRS, Région wallonne and Televie. NL received speaker fees from Gilead Sciences and Fresenius Kabi; received travel grants from Abbvie, Gilead Sciences and Norgine and receives grants from Gilead Sciences. AL has no conflict of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Fig. 1
Fig. 1

Potential pathophysiological mechanisms, phenotypic description and consequences of myosteatosis in MASLD. MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 2
Fig. 2

Flow chart of the selection of original manuscripts for inclusion in this systematic review. MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 3
Fig. 3

Pathophysiological mechanisms involved in myosteatosis pathogenesis in MASLD. MASLD, metabolic dysfunction-associated steatotic liver disease.

Fig. 4
Fig. 4

Signalling pathways involved in the cellular lipotoxicity related to myosteatosis in MASLD. AMPK, AMP-activated protein kinase; CPT1, carnitine palmitoyltransferase 1; DAG, diacylglycerol; GLUT4, glucose transporter 4; IL, interleukin; IRS, insulin receptor substrate; MAPK, mitogen-activated protein kinase; MASLD, metabolic dysfunction-associated steatotic liver disease; Myd88, myeloid differentiation factor 88; NLRP3, NOD-like receptor family, pyrin domain containing 3; PDK1, 3-phosphoinositide-dependent protein kinase 1; PGC1α, peroxisome proliferator-activated receptor gamma 1 α; PLIN5, perilipin 5; PI3K, phosphatidylinositol-3-kinase; PKC, protein kinase C; TLR4, Toll-like receptor 4; TNFα, tumour necrosis factor α.

Fig. 5
Fig. 5

Mediators of the muscle-liver-adipose tissue axis promoting myosteatosis in MASLD. Adiponectin serum level decreases in MASLD, increasing liver and muscle lipid contents. Cathepsin D serum level increases in MASLD, promoting systemic inflammation. Musclin serum level decreases in MASLD, increasing liver lipid content. Seleprotein P serum level increases in MASLD, increasing liver and muscle lipid contents and decreasing adiponectin expression. Systemic inflammation and insulin resistance occurring in MASLD reciprocally promote an increase in muscle and liver lipid contents as well as adipose tissue expansion. IFNα2, interferon-α2; IL15, interleukin 15; IL1α, interleukin-1α; MASLD, metabolic dysfunction-associated steatotic liver disease; SeP, selenoprotein P; TGFβ, transforming growth factor β; TNFα, tumour necrosis factor-α.

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