Epimuscular fat and its clinical relevance: a narrative review focused on paraspinal muscles

Introduction

In recent years, research on degenerative muscular processes associated with myosteatosis conditions has progressively expanded beyond the sole concept of intramuscular fat (IF), increasingly focusing on epimuscular fat (EF). This tissue, located outside the epimysial boundary between the paraspinal muscles, particularly the erector spinae and multifidus, and the thoracolumbar fascia (1,2), is distinct from IF, which exists within the muscle fascia between muscle fibers (Figure 1). EF seems to play a crucial role in muscle biomechanics, potentially influencing force transmission and intermuscular connectivity. Its structural importance has been recognized as a cornerstone for proper muscle function (3).

Figure 1 Axial T2-weighted MRI of the lumbar spine showing the CSA of the paraspinal muscles. The right muscle compartment is outlined in yellow and the left in blue. EF is not highlighted in this segmentation. CSA, cross-sectional area; EF, epimuscular fat; MRI, magnetic resonance imaging.

EF is present in regions such as the rotator cuff and lumbar spine, showing both similarities and differences with other fat depots like epicardial fat (4). It is not a static tissue but rather a dynamic one, capable of mobilizing progenitor cells such as adipose-derived stem cells (ASCs) (5,6), and exhibits thermogenic characteristics similar to brown/beige adipose tissue (6). In the rotator cuff, where molecular studies have been mostly concentrated, EF is associated with chronic injuries that significantly impact both muscle architecture and repair outcomes (6). In the lumbar spine, it is correlated with low back pain (LBP), particularly at lower levels (L4–S1) (7). These results highlight the clinical importance of this tissue, making it a potential target for therapeutic strategies.

Advancements in imaging have clarified and validated the role of EF, which is now increasingly included in region of interest (ROI) assessments of cross-sectional areas (CSA) (8). Furthermore, given the recent reevaluation of this tissue, there is a growing call for standardized imaging protocols (9).

According to these findings, this review aims to comprehensively analyze current knowledge regarding the molecular, structural, and functional characteristics of EF, with particular attention to its biomechanical impact and its potential role in the onset or persistence of clinical conditions such as LBP. The review also addresses ongoing scientific discussions around segmentation and current studies of EF through magnetic resonance imaging (MRI). The goal is to provide an updated and multidimensional overview of a tissue that remains relatively unknown yet and that is gaining increasing interest in the context of muscle pathophysiology. This review analyzes studies in order to highlight the importance of epimuscular adipose tissue, particularly in the rotator cuff muscles and paraspinal regions. We present this article in accordance with the Narrative Review reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1180/rc).

Methods

Search strategy

This narrative review was based on a structured literature search of the current evidence. The literature search was performed in May 2025 using electronic databases, including PubMed, Cochrane Library, and Scopus. The search utilized the following keywords: “epimuscular” and “fat”. Additionally, a manual search was conducted via Google Scholar and by reviewing the reference lists of eligible articles identified in the database search. No restrictions were placed on the publication date range for the search.

The literature search strategy is summarized in Table 1.

The literature search was originally based on the term ‘epimuscular fat’ to ensure consistency in anatomical definition. However, during manuscript revision, we also reviewed studies referring to ‘intermuscular adipose tissue’ (IMAT) and ‘peri-muscular adipose tissue’ (PMAT), which describe closely related extra-fascial fat depots. Only studies explicitly using the term ‘epimuscular fat’ were included in the summary tables, while IMAT and PMAT literature was discussed qualitatively to highlight their anatomical and functional overlap.

Study selection

Duplicate articles were removed, and the titles and abstracts of the remaining studies were screened to assess their relevance to the selection criteria. Full-text articles that passed this initial screening were evaluated based on specific inclusion standards. Studies were included if they: (I) investigated EF or related parameters; (II) recruited participants aged 18 years or older; (III) employed MRI as the imaging modality or histological analysis; and (IV) were published in English. Exclusion criteria included: review articles, preclinical studies, and case reports. The complete study selection process is depicted in (Figure 2).

Figure 2 Flowchart of literature search and study selection.

Data extraction

The extracted data included the following details: author and year of publication, study design, number of participants, imaging technique used, and study results. These details were organized and documented in a table created with word processing software.

Results

The systematic search resulted in a total of 7 articles. After removing duplicates, the remaining articles were screened for inclusion criteria based on title and abstract and, if necessary, full text. At the end of the complete screening, 7 articles were selected.

Study characteristics are reported in Table 2. Among the seven studies included, different study designs and imaging techniques were employed. One study (7) was a retrospective case-control study and utilized lumbosacral MRI with DIXON or IDEAL fat-water sequences to compare the presence and extent of EF between chronic LBP patients and healthy controls. This study (7) reported significantly higher EF at the L4–L5 and L5–S1 levels in patients with LBP, with strong correlations to body mass index (BMI) and moderate correlations to age.

Another retrospective observational study (2) used T2-weighted axial MRIs at the mid-L4 vertebra to compare two methods for defining ROI in lumbar paraspinal muscles. Including EF resulted in larger total cross-sectional areas (tCSA) and higher fat signal fraction (FSF), highlighting the importance of method selection in evaluating fat accumulation (Figure 3).

Figure 3 Axial T2-weighted MRI of a lumbar segment showing the segmentation of the paraspinal muscles (multifidus and erector spinae), including the epimuscular fat highlighted in orange on the right and in blue on the left. MRI, magnetic resonance imaging.

A cross-sectional study (10) of highly active individuals employed multiparametric MRI, including high-resolution anatomical scans, IDEAL fat-water separation scans, and diffusion tensor imaging (DTI). This study observed that EF was predominantly located in the lower lumbar spine (L3–L5), forming distinct patterns such as “fatty tents” in posterior regions, with minimal IF present.

Another retrospective cross-sectional study (11) using T2-weighted axial MRIs of the lumbar spine from L1 to L5 showed significantly higher EF at lower lumbar levels (L4 and L5) compared to upper levels (L1 and L2). This fat was strongly correlated with BMI and moderately associated with age. The study also found a significant relationship between EF and LBP intensity in adjusted analyses.

A methodological study (9) focused on segmentation protocols for lumbar paraspinal muscles used axial T2-weighted and fat-water separation (IDEAL) MRIs acquired with a 3T scanner. It highlighted that including EF in segmentation protocols significantly impacted measurements of muscle size and fat composition, emphasizing the need for standardized protocols to ensure consistency across studies.

In 2023, Parson et al. (12) conducted an experimental study on uncoupling protein 1 (UCP1)⁺ cell ablation (UCP1-DTA) and wild type mice using histological analysis, Oil Red O staining, and confocal microscopy to investigate the role of UCP1-lineage cells in intramuscular adipose tissue development and expansion. The results showed that EF exhibited UCP1 positivity, confirming a brown/beige adipose phenotype. In contrast, IF does not rely on UCP1-lineage cells for development, and glycerol-induced injury did not affect UCP1 presence in intramuscular adipose tissue (12).

Lastly, an observational and experimental study (6) on rotator cuff pathology identified EF as a novel beige fat depot with distinct properties compared to subcutaneous fat. While this study did not focus on the lumbar spine, it contributed valuable insights into the biological and functional properties of EF.

Overall, most studies used MRI as the primary imaging modality, but with varying sequences such as DIXON, IDEAL, and T2-weighted imaging. The findings consistently demonstrated that EF is a key feature associated with lumbar pathology, particularly in the context of chronic LBP, and its presence correlates with BMI, age, and disease severity.

Imaging techniques and software analysis are summarized in Table 3.

Discussion

Molecular characteristics of EF

Over the years, numerous studies have led to a better understanding of EF. To frame the histological nature of EF, it is necessary to perform a differential analysis between two entities: brown adipose tissue and white adipose tissue. The former has a distinct cellular origin compared to white fat and is more associated with muscle, with a role in heat dissipation using chemical energy, whereas the latter functions as an energy reserve in the form of triglycerides (13-15). Although these are two separate entities, rodent studies have shown that some white fat depots can undergo a “browning” process, acquiring intermediate characteristics between white and brown fat in response to specific stimuli (16,17), giving rise to a third intermediate entity: beige fat. The origin of this tissue in humans remains a topic of debate, with ongoing questions about whether it derives from specialized brown depots, transdifferentiated white fat, or represents a distinct subgroup (18,19).

The study by Meyer et al. (6) compared this tissue with subcutaneous fat, which is typically white, concluding that EF represents a novel depot of beige fat. In fact, EF shows UCP1 expression levels that are 2 to 10 times higher than those of subcutaneous fat, although still lower than classical brown fat depots (20). Meyer et al. (6) found that EF adipocytes were one-fifth the size of subcutaneous adipocytes and predominantly unilocular. Stem cells derived from EF retained the genetic characteristics of their tissue of origin and showed high proliferation capacity in culture, with higher expression of brown fat-associated genes (UCP1, LHX8, CITED1, CIDEA) and the transcriptional regulator PRDM16.

Lastly, the study by Parson et al. (12) highlighted differences between IF and EF through analysis of UCP1 protein. The study revealed that IF does not express UCP1 either in physiological or pathological conditions, confirming it as a type of white fat. Conversely, EF in murine models showed UCP1 positivity, resembling classical brown and beige fat depots. Additionally, following a β3-adrenergic stimulus on IF, UCP1 activation was found to be both limited and localized. Conversely, EF in murine models showed UCP1 positivity, resembling classical brown and beige fat depots.

Different naming conventions have been used to describe adipose tissue adjacent to skeletal muscle. Ogawa et al. (21) defined IMAT as fat located beneath the deep fascia and between adjacent muscle groups, while Yoshiko et al. (22) reported IMAT changes in immobilization models and Khoja et al. (23) examined IMAT accumulation in rheumatoid arthritis. Conversely, Zhu et al. (24) described PMAT as ectopic fat surrounding skeletal muscle that accelerates atrophy in aged and obese mice, whereas Khan et al. (25) reported PMAT in association with insulin resistance, and Morrison et al. (26) described its relationship with metabolic alterations in women with polycystic ovary syndrome. Although these definitions are not anatomically identical, they all refer to a functionally similar extra-fascial adipose compartment, distinct from both subcutaneous and IF, and closely related to what we describe here as EF.

Investigation of epimuscular adipose tissue in the spinal region

EF is an adipose tissue located near muscles and potentially capable of influencing their function and biomechanics. Recently, a possible implication of EF in LBP has been hypothesized, although the relationship between the two is not yet fully understood.

Unlike IF, which is distributed among muscle fibers within the fascial boundaries, EF is located externally and may affect muscle biomechanics, force generation, and intermuscular interactions (3). The exact connection between EF and LBP remains unclear: EF might alter muscle mechanics, potentially triggering or maintaining LBP, or it might represent an adaptive change in response to muscle dysfunction associated with LBP. The specific nature of the relationship between EF and LBP, as well as its variation across different spinal regions, has not been fully elucidated.

A study by Vitale et al. (11) observed the presence of EF in most individuals across all lumbar levels. Its prevalence increased from L1 (77.5%) to L3 and L4 (100%), then slightly decreased at L5 (95.0%). No significant differences were found in EF quantity between the right and left sides or between males and females, except at L5, where the right side showed a greater EF volume than the left (22.5 mm², P=0.008). Qualitative assessments of EF also showed no significant variation based on side or sex.

EF quantity varied significantly across lumbar levels (P<0.0001), with larger amounts at lower levels (L4: 253.1 mm²; L5: 220.2 mm²) compared to upper levels (L1: 36.1 mm²; L2: 72.2 mm²). Total EF was strongly correlated with BMI (quantitative rs: 0.65; qualitative rs: 0.69; P<0.001). Moderate correlations were observed between EF and fatty infiltration (quantitative rs: 0.31, P=0.04; qualitative rs: 0.37, P=0.01) and between age and qualitative EF scores (rs: 0.33, P=0.03) in unadjusted analyses; however, these correlations became non-significant after statistical adjustments. Conversely, adjusted analyses revealed a significant relationship between LBP and total quantitative EF (rs: 0.31, P=0.04) (11).

Rosenstein et al. (7) examined EF distribution and volume in subjects with chronic LBP compared to healthy controls (except for BMI, which was significantly higher), exploring associations between EF levels, spinal regions (L1 to L5), BMI, age, sex, symptom duration, and LBP severity. The study first established measurement reliability, reporting intra-rater reliability >0.75 for CSA identification and >0.90 for fat percentage measurement.

A significant correlation was found between qualitative EF scores and chronic LBP at L4–L5 and L5–S1 bilaterally. Additionally, total qualitative EF scores from L2 to L5 were positively correlated with BMI, female sex, and LBP status in both unadjusted and adjusted analyses, while age showed only a weak positive correlation in the unadjusted analysis that became non-significant when adjusted. The quantitative EF area (L2–L5) was strongly correlated with BMI and age in both adjusted and unadjusted analyses but did not show a significant relationship with sex. In the unadjusted analysis, LBP showed a weak but significant correlation with quantitative EF area, which became non-significant after adjustment. No significant associations were found between LBP duration or intensity and total qualitative EF scores or EF area.

In radiology, three major studies (2,9,10) used MRI to explore the specific features of EF and provide initial tools for its analysis.

Two of these studies (2,10) offer complementary perspectives on MRI evaluation of lumbar muscles, particularly concerning EF. In 2018, Berry et al. (2) compared two methods for defining the ROI in axial MRI scans of the paraspinal muscles. The main difference between the approaches was the inclusion or exclusion of EF. Both methods showed high inter-rater reliability (ICC >0.75). Method 1, which included EF, produced significantly higher measurements for tCSA and FSF, with increases of 14–15% and 11–13%, respectively, in the erector spinae and a 4% increase in tCSA for the multifidus. In contrast, Method 2, which excluded EF, provided more specific information on IF infiltration by focusing on changes within the epimysial boundary. The method chosen has to do with research goals: whether to assess broader factors like atrophy and fat accumulation, or to focus specifically on IF infiltration.

In 2020, Berry et al. (10) conducted a study to establish reference values for muscle volume, FSF, and restricted diffusion in the lumbar muscles of an active population using DTI MRI. The study highlighted variations across vertebral levels: the multifidus and erector spinae muscles differed in size, fat content, and diffusion along the lumbar spine. The erector spinae showed slightly higher FSF than the multifidus (0.228 vs. 0.205), with a progressive FSF increase from L1 (0.188) to S1 (0.338). Additionally, FSF in the multifidus was significantly higher than in the erector spinae at L1–L3 (P<0.0116), but significantly lower at L4–S1 (P<0.0001).

3D reconstructions revealed greater EF accumulation in the lower lumbar spine compared to upper segments. MRI thus proved effective in capturing both microstructural and macrostructural variations in healthy lumbar muscles.

Finally, the PILLAR study (ParaspInaL muscLe segmentAtion pRoject) by Anstruther et al. (9) emphasizes the critical role of MRI-based standardized protocols in analyzing the morphology and composition of paraspinal muscles, particularly in the context of LBP. Addressing inconsistencies in imaging approaches, such as the inclusion (8) or exclusion (27) of EF within the CSA ROI as examined in Berry’s 2018 study (2), the PILLAR study highlights the importance of segmentation for understanding demographic and pathological variations, including increased fat infiltration in older adults, women, and individuals with chronic LBP. Using ITK-SNAP software, the project standardizes protocols for segmenting lumbar muscles (multifidus, erector spinae, quadratus lumborum, and psoas major) paving the way for automated tools to improve research precision and clinical application. This initiative is essential for providing consistent biomarkers for diagnosis, classification, and potential prediction of lumbar spine pathologies.

This narrative review highlights that the current literature on EF is still in its early stages. The number of available studies is limited, reflecting the novelty of this research area. Included studies differ in design, ranging from cross-sectional and retrospective observational analyses to experimental and methodological investigations, and show considerable heterogeneity in imaging techniques, segmentation protocols, and study populations. Such variability limits direct comparison across studies and challenges the generalizability of findings. Additionally, all available studies are observational, and no longitudinal or interventional research has yet explored the causal relationship between EF accumulation and clinical outcomes such as LBP. These limitations underscore the need for standardized imaging protocols and prospective studies with larger, well-defined populations to better understand the pathophysiological role of EF and its potential as a diagnostic or therapeutic target. Recent studies have further emphasized the interplay between paraspinal muscle degeneration, bone health, and mechanical complications of spinal disorders, supporting the clinical relevance of fatty changes around the spine (28,29).

Conclusions

EF represents an emerging area of interest in musculoskeletal research, particularly regarding its role in spinal biomechanics and LBP. This systematic review identifies EF as a distinct adipose depot that differs from IF in localization, structure, and function. Accumulating evidence suggests that EF is more prevalent in the lower lumbar spine (L4–S1) and is strongly correlated with BMI, age, and LBP severity. However, the precise mechanisms by which EF influences spinal stability and muscle function remain unclear.

The reviewed studies emphasize the importance of standardized imaging protocols to accurately quantify EF and assess its clinical relevance. Molecular evidence suggests that EF shares properties with beige adipose tissue, indicating a potential metabolic role that warrants further investigation. While EF may contribute to biomechanical dysfunction in LBP, it remains uncertain whether its presence is a cause or consequence of muscle pathology.

Future research should prioritize longitudinal studies to determine the causal relationship between EF accumulation and LBP. Additionally, exploring EF as a therapeutic target, such as through interventions aimed at modifying its composition or distribution, could provide novel strategies for managing spinal disorders. A deeper understanding of EF’s role in muscle health and pathology may ultimately improve diagnostic accuracy and treatment options for LBP and other musculoskeletal conditions.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1180/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1180/coif). C.A.M. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All clinical procedures described in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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