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Review
. 2024 Feb 15;27(3):109221.
doi: 10.1016/j.isci.2024.109221. eCollection 2024 Mar 15.

Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism

Liyi Wang  1   2   3 , Teresa G Valencak  1 , Tizhong Shan  1   2   3
Affiliations
Review

Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism

Liyi Wang et al. iScience. .

Abstract

Fat infiltration in skeletal muscle (also known as myosteatosis) is now recognized as a distinct disease from sarcopenia and is directly related to declining muscle capacity. Hence, understanding the origins and regulatory mechanisms of fat infiltration is vital for maintaining skeletal muscle development and improving human health. In this article, we summarized the triggering factors such as aging, metabolic diseases and metabolic syndromes, nonmetabolic diseases, and muscle injury that all induce fat infiltration in skeletal muscle. We discussed recent advances on the cellular origins of fat infiltration and found several cell types including myogenic cells and non-myogenic cells that contribute to myosteatosis. Furthermore, we reviewed the molecular regulatory mechanism, detection methods, and intervention strategies of fat infiltration in skeletal muscle. Based on the current findings, our review will provide new insight into regulating function and lipid metabolism of skeletal muscle and treating muscle-related diseases.

Keywords: Health sciences; Human metabolism; Physiology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

None
Graphical abstract
Figure 1
Figure 1
Influential triggers on fat infiltration in skeletal muscle Several triggering factors induce IMF deposition in skeletal muscle, including aging, diseases, muscle injury, and others. COPD, chronic obstructive pulmonary disease; DMD, duchenne muscular dystrophy; HIV, Human immunodeficiency virus; NO, nitric oxide; T2D, type 2 diabetes.
Figure 2
Figure 2
Fat infiltration in skeletal muscle derived from cell types with myogenic or non-myogenic origins ScRNA-seq, snRNA-seq, genetic lineage tracing, in vitro cell culture models, and microscopy represent classical tools for studying the formation of fat infiltration in skeletal muscle and have found myogenic cells and non-myogenic cells types lead to fat infiltration. ECs, endothelial cells; FAPs, fibro/adipogenic progenitors; MSCs, mesenchymal stem cells; PICs, PW1-expressing cells; SCs, satellite cells; scRNA-seq, single-cell RNA sequencing; snRNA-seq, single-nucleus RNA sequencing; SPs, side population cells. Reprinted from Copyright 2020, Wiley Online Library; Copyright 2023, Springer nature; Copyright 2023, Wiley Online Library; under the Creative Commons CC BY License.
Figure 3
Figure 3
Molecular mechanism of fat infiltration in skeletal muscle Regulation of IMF deposition involves in many genes and signaling pathways including cAMP-PKA, hedgehog, Wnt/β-catenin, AMPK, MAPK, miRNAs, and lncRNAs. ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; aP2, adipocyte fatty acid-binding protein; ATGL, adipose triglyceride lipase; cAMP-PKA, cAMP-protein kinase A; CASR, calcium-sensing receptor; CREB, cAMP response element-binding protein; CRTCs, CREB-regulated transcription coactivators; CTRP6, C1q/tumor necrosis factor-related protein 6; DGAT1, diacylglycerol acyltransferase 1; DNJ, 1-deoxynojirimycin; ERK, e extracellular signal-regulated kinases; FABP4, fatty acid-binding protein 4; GADD45A, growth arrest and DNA damage-inducible alpha; IMF, intramuscular fat; LKB1, liver kinase B1; MAPK, mitogen-activated protein kinase; miRNAs, microRNAs; PPARγ, peroxisome proliferator-activated receptors γ; PRMT5, protein arginine methyl transferase 5; SREBP1a, sterol regulatory element-binding transcription factor 1a; TAZ, transcriptional co-activator with PDZ-binding motif; YAP, Yes-associated protein.
Figure 4
Figure 4
The balance between sarcopenia and exercise under different conditions The effects of exercise on regulating fat infiltration in skeletal muscle under health, pathological, physiological aging, and aging with pathological conditions.
See this image and copyright information in PMC

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