Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism

Wang, Liyi; Valencak, Teresa G.; Shan, Tizhong

doi:10.1016/j.isci.2024.109221

Cited by 16 publications

(5 citation statements)

References 158 publications

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“…1a ). Correlation analysis identified that the protein expression of ADIPOQ, PLIN1, and FABP4 and the gene expression of ADIPOQ , PPARG , and FABP4 were positively related to age 34 (Fig. 1b ).…”

Section: Resultsmentioning

confidence: 97%

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Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles

Wang,

Zhou,

Wang

et al. 2024

Sci Data

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Fat infiltration in skeletal muscle is now recognized as a standard feature of aging and is directly related to the decline in muscle function. However, there is still a limited systematic integration and exploration of the mechanisms underlying the occurrence of myosteatosis in aging across species. Here, we re-analyzed bulk RNA-seq datasets to investigate the association between fat infiltration in skeletal muscle and aging. Our integrated analysis of single-nucleus transcriptomics in aged humans and Laiwu pigs with high intramuscular fat content, identified species-preference subclusters and revealed core gene programs associated with myosteatosis. Furthermore, we found that fibro/adipogenic progenitors (FAPs) had potential capacity of differentiating into PDE4D+/PDE7B+ preadipocytes across species. Additionally, cell-cell communication analysis revealed that FAPs may be associated with other adipogenic potential clusters via the COL4A2 and COL6A3 pathways. Our study elucidates the correlation mechanism between aging and fat infiltration in skeletal muscle, and these consensus signatures in both humans and pigs may contribute to increasing reproducibility and reliability in future studies involving in the field of muscle research.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles

Wang,

Zhou,

Wang

et al. 2024

Sci Data

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“…The phenomenon of the athlete's paradox in which IMCLs are increased in both athletes and obese individuals is a noted example of this complexity (Li et al., 2019 ). While a full review of the cellular origin and pathways of fat infiltration is beyond the scope of this paper, it has been recently extensively reviewed elsewhere (Wang et al., 2024 ). The opportunity for ectopic fat depots to infiltrate dysfunctional muscle tissue (Goodpaster & Wolf, 2004 ) contributes to the development of myosteatosis, though it appears to be more complex than just the mere replacement of muscle fibers with adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

The effects of myosteatosis on skeletal muscle function in older adults

Dondero,

Friedman,

Rekant

et al. 2024

Physiological Reports

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Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults. Myosteatosis and its inflammatory milieu play a larger role in adipose tissue dysfunction, muscle tissue dysfunction, and increased passive muscle stiffness. Combined with the age‐related decline of sex hormones and development of anabolic resistance, myosteatosis also contributes to insulin resistance, impaired muscle mechanics, loss of force production from the muscle, and increased risk of chronic disease. Due to its highly inflammatory secretome and the downstream negative effects on muscle metabolism and mechanics, myosteatosis has become an area of interest for aging researchers and clinicians. Thus far, myosteatosis treatments have had limited success, as many lack the potency to completely rescue the metabolic and physical consequences of myosteatosis. Future research is encouraged for the development of reliable assessment methods for myosteatosis, as well as the continued exploration of pharmacological, nutritional, and exercise‐related interventions that may lead to the success in attenuating myosteatosis and its clinical consequences within the aging population.

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“…Besides, fat infiltration in skeletal muscle (also known as myosteatosis) is the pathologic fat accumulation in skeletal muscle with poor metabolic and musculoskeletal health, it always accompanied by the decline of muscle quality and function(Biltz et al, 2020; Jiang, Marriott, & Maly, 2019). Myosteatosis is now considered as a common feature of ageing and is also related to some diseases(Wang, Valencak, & Shan, 2024). However, the occurrence mechanism and cell sources of fat accumulation in skeletal muscle is very complicated.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, more and more researches have been focusing on exploring the regulatory mechanism of myosteatosis at the cytological levels. Besides, fat infiltration in skeletal muscle is regulated by many influential triggers, including ageing, metabolic and nonmetabolic diseases, disuse and inactivity, and muscle injury(Wang et al, 2024). Many genes and signaling pathways participate in the formation and regulation of fat infiltration in skeletal muscle (Biferali et al, 2021; Wosczyna et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

Wang,

Liu,

Zhang

et al. 2024

Preprint

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Conjugated linoleic acids (CLAs) can serve as a nutritional intervention to regulate quality, function and fat infiltration in skeletal muscles but the specific cytological mechanisms are still unknown. Here, we applied single-nucleus RNA-sequencing (snRNA-seq) to characterize the cytological mechanism of CLAs regulates fat infiltration in skeletal muscles based on pig models. We investigated the regulatory effects of CLAs on cell populations and molecular characteristics in pig muscles and found CLAs could promote the transformation of fast glycolytic myofibers into slow oxidative myofibers. We also observed three subpopulations including SCD+/DGAT2+, FABP5+/SIAH1+, and PDE4D+/PDE7B+subclusters in adipocytes and CLAs could increase the percentage of SCD+/DGAT2+adipocytes. RNA velocity analysis showed FABP5+/SIAH1+and PDE4D+/PDE7B+adipocytes could differentiate into SCD+/DGAT2+adipocytes. We further verified the differentiated trajectory of mature adipocytes and identified PDE4D+/PDE7B+adipocytes could differentiate into SCD+/DGAT2+and FABP5+/SIAH1+adipocytes by using high IMF content Laiwu pig models. The cell-cell communication analysis identified the interaction network between adipocytes and other subclusters such as fibro/adipogenic progenitors (FAPs). Pseudotemporal trajectory analysis and RNA velocity analysis also showed FAPs could differentiate into PDE4D+/PDE7B+preadipocytes and we discovered the differentiated trajectory of preadipocytes into mature adipocytes. Besides, we found CLAs could promote FAPs differentiate into SCD+/DGAT2+adipocytes via inhibiting c-Jun N-terminal kinase (JNK) signalling pathwayin vitro. This study provides a foundation for regulating fat infiltration in skeletal muscles by using nutritional strategies and provides potential opportunities to serve pig as an animal model to study human fat infiltrated diseases.

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Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism

Cited by 16 publications

References 158 publications

Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles

Integrative cross-species analysis reveals conserved and unique signatures in fatty skeletal muscles

The effects of myosteatosis on skeletal muscle function in older adults

Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

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