Myosteatosis and Dyslipidemia: Linking Muscle Quality to Cardiometabolic Risk

Abstract

Myosteatosis, the pathological accumulation of ectopic fat within skeletal muscle, has emerged as a key indicator of impaired muscle quality and metabolic dysfunction. It encompasses intermuscular and intramuscular adipose tissue as well as intramyocellular lipid, which differ in anatomical location, assessment methodology, and metabolic role. This review provides an integrated overview of myosteatosis, focusing on its bidirectional relationship with dyslipidemia. Myosteatosis represents a metabolically active fat depot characterized by heightened lipolytic and pro-inflammatory activity. It serves not only as an energy substrate for muscle contraction but also as a source of lipotoxic intermediates that impair insulin signaling. Dyslipidemia has been proposed to contribute to lipid overflow and ectopic fat deposition in skeletal muscle, whereas myosteatosis-induced insulin resistance may, in turn, be linked to increased hepatic de novo lipogenesis, potentially contributing to atherogenic dyslipidemia. Epidemiological studies consistently demonstrate associations between myosteatosis and adverse lipid profiles across populations, although the magnitude and specificity of these associations vary by sex, age, ethnicity, and accompanying adipose depots such as visceral fat. Most available evidence remains cross-sectional, and standardized quantification methods are lacking. Future longitudinal and interventional studies are needed to clarify causality, define diagnostic thresholds, and determine whether improving muscle quality can mitigate cardiometabolic risk. Incorporating myosteatosis assessment into clinical practice may enhance metabolic risk stratification beyond conventional measures of muscle mass and adiposity.

INTRODUCTION

Skeletal muscle serves as a principal site for glucose uptake and storage,¹,² as well as fatty acid oxidation and metabolism.³ Under conditions of positive energy balance, the capacity of adipose tissue for healthy expansion may become saturated, leading to ectopic fat deposition in non-adipose tissues, including skeletal muscle.⁴

Myosteatosis refers to the accumulation of ectopic fat within skeletal muscle. The concept initially arose from studies examining skeletal muscle composition in neuromuscular disorders such as Duchenne muscular dystrophy.⁵ Subsequent research extended this focus to metabolic conditions, including obesity and aging, using both muscle biopsy⁶ and imaging techniques such as computed tomography (CT).⁷

Following the recognition of sarcopenia as an independent disease entity with its own International Classification of Diseases, 10th Revision code in 2016,⁸ its definition evolved from one based solely on muscle mass to incorporating muscle function, which more accurately predicts clinical outcomes.⁹,¹⁰,¹¹,¹² This shift has drawn attention to myosteatosis as a key determinant of both muscle function and metabolic health. Advances in imaging modalities—particularly CT and magnetic resonance imaging (MRI)—together with artificial intelligence–based analytical approaches, have further enabled precise quantitative assessment of myosteatosis.¹³,¹⁴,¹⁵

This review provides an updated understanding of myosteatosis, with a particular focus on its interplay with dyslipidemia. We first define myosteatosis and outline current quantification methods. We then examine the pathophysiological role and bidirectional relationship with dyslipidemia, summarize major findings from epidemiological studies, and discuss ongoing challenges and future research directions in this rapidly evolving field.

DEFINITION OF MYOSTEATOSIS

Myosteatosis can be classified according to the anatomical location of fat deposition within skeletal muscle (Fig. 1). Intermuscular adipose tissue refers to fat located beneath the fascia and between distinct muscle groups and is sometimes termed perimuscular adipose tissue. Intramuscular adipose tissue, also known as extramyocellular lipid, describes adipose tissue infiltrating the interstitial spaces within individual muscles. Collectively, inter- and intramuscular adipose tissue (IMAT) represents macroscopic fat accumulation in skeletal muscle. In contrast, intramyocellular lipid (IMCL) denotes lipid droplets stored within the cytoplasm of individual muscle fibers.¹²,¹⁶

Fig. 1. Anatomical classification of myosteatosis within skeletal muscle. IMAT is located between muscle groups and beneath the fascia. IMCL is deposited within muscle fibers. Created in BioRender (https://BioRender.com/zn216fw).

IMAT, inter- and intramuscular adipose tissue; IMCL, intramyocellular lipid; EMCL, extramyocellular lipid.

MEASUREMENT OF MYOSTEATOSIS

Myosteatosis was traditionally assessed through muscle biopsy.¹⁷ In recent years, however, noninvasive imaging modalities such as CT, MRI, and quantitative ultrasound (US) have become essential tools for visualizing overall fat distribution within skeletal muscle, overcoming the invasiveness and sampling limitations of biopsy. While IMAT can be readily detected using CT or MRI, IMCL is more difficult to visualize directly and requires magnetic resonance spectroscopy (MRS) or histological analysis.¹² Alternatively, IMCL can be estimated indirectly using muscle density or attenuation values, which correlate strongly with microscopic lipid accumulation.¹⁸ Accordingly, comprehensive evaluation of myosteatosis typically integrates macroscopic fat quantification (e.g., IMAT area) with indirect imaging surrogates of microscopic lipid infiltration (e.g., muscle density or attenuation indices). The selection of the muscle group for assessment also influences interpretation. Thigh muscles are frequently analyzed due to their accessibility and validation in biopsy studies, whereas pelvic girdle and abdominal muscles are increasingly recognized as more representative of overall muscle quality.¹⁵ Despite these advances, no standardized imaging protocol, device, or diagnostic cutoff has yet been universally established for myosteatosis quantification.

CT is among the most widely utilized imaging modalities owing to its high reproducibility and the potential for opportunistic assessment from scans performed for other clinical purposes.¹² Both the IMAT area and muscle attenuation (MA) can be evaluated on CT images. The IMAT area is generally defined using attenuation thresholds between −190 and −30 Hounsfield units (HU).¹⁴ Beyond IMAT, MA itself serves as a surrogate marker of myosteatosis, with lower attenuation values indicating greater IMCL infiltration. Skeletal muscle is typically defined with an attenuation range of −29 to 150 HU. Myosteatosis is often operationally defined as MA <41 HU for individuals with a body mass index (BMI) of <25 kg/m² and MA of <33 HU for those with a BMI of ≥25 kg/m².¹⁴,¹⁹ Alternatively, cutoff values derived from T-scores of various indices have also been proposed—most notably, the normal attenuation muscle area (NAMA)–to–total abdominal muscle area (TAMA) ratio.¹³,²⁰ A higher NAMA/TAMA index reflects lower fat infiltration and therefore better muscle quality. Given that both values are derived under identical imaging conditions, this ratio minimizes contrast-induced variability in MA,²¹,²² which would otherwise necessitate correction through calibration phantoms or normalization to subcutaneous fat attenuation values.²³,²⁴,²⁵ The NAMA/TAMA index correlates closely with body fat distribution and visceral adiposity and has demonstrated significant clinical relevance across multiple metabolic and cardiovascular conditions, including metabolically unhealthy phenotypes,²⁶ sarcopenic obesity,²⁷ hypertension,²⁸ insulin resistance and type 2 diabetes,²⁹,³⁰ metabolic dysfunction–associated steatotic liver disease,³¹ and subclinical coronary atherosclerosis.³²

PATHOPHYSIOLOGIC MECHANISMS AND METABOLIC ROLES OF MYOSTEATOSIS

1. Pathophysiologic roles of IMAT

The proposed cellular origins of IMAT include muscle-resident satellite stem cells, fibro-adipogenic progenitor cells, adipose-derived stem cells migrating from adjacent depots, and bone marrow-derived mesenchymal stem cells.³³,³⁴,³⁵

IMAT is increasingly recognized as a metabolically active adipose depot. In vitro studies have demonstrated that its lipolytic rate is comparable to that of visceral adipose tissue (VAT) and nearly 3-fold higher than that of subcutaneous adipose tissue,³⁶ resulting in increased release of free fatty acids that disrupt insulin signaling. This heightened lipolytic activity may be partly attributable to reduced expression of perilipin-5, a lipid droplet–associated protein that functions as a barrier to lipolysis and is downregulated in insulin-resistant states.³⁶ In addition, IMAT secretes a range of pro-inflammatory cytokines, chemokines, and eicosanoids that promote local inflammation and further impair insulin sensitivity (Fig. 2A).³⁴,³⁵,³⁷,³⁸,³⁹ Together, these features characterize IMAT as a distinct ectopic fat compartment within skeletal muscle, with pronounced lipolytic and inflammatory activity that may link local fat infiltration to systemic metabolic dysfunction.

Fig. 2. The relationship between myosteatosis, insulin resistance, and atherogenic dyslipidemia. (A) IMAT: lipolytic and inflammatory properties. IMAT is a metabolically active ectopic fat depot characterized by high lipolytic activity and secretion of pro-inflammatory mediators, promoting local free fatty acid release and inflammation within skeletal muscle. (B) IMCL: intracellular lipotoxic signaling. IMCL accumulation serves as a precursor pool for lipotoxic intermediates such as DAG and ceramides, particularly under conditions of mitochondrial dysfunction and incomplete fatty acid oxidation. These intermediates impair insulin signaling through oxidative stress and inflammatory pathways. (C) Myosteatosis and dyslipidemia. Myosteatosis is associated with skeletal muscle insulin resistance and reduced postprandial glucose uptake, redirecting excess substrates to the liver and enhancing hepatic de novo lipogenesis. Lipid overflow may further contribute to ectopic fat deposition in skeletal muscle, reinforcing a bidirectional pathogenic cycle between myosteatosis and atherogenic dyslipidemia. Created in BioRender (https://BioRender.com/22u4ts3).

IMAT, inter- and intramuscular adipose tissue; IMCL, intramyocellular lipid; DAG, diacylglycerol; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; ATGL, adipose triglyceride lipase; HSL, hormone-sensitive lipase; PLIN5, perilipin-5; ROS, reactive oxygen species; TAG, triacylglycerol; TG, triglyceride; HDL-C, high-density lipoprotein-cholesterol.

2. Pathophysiologic roles of IMCL

IMCL consists primarily of intramuscular triglycerides (TGs) stored within muscle fibers. The breakdown of these lipid stores is sequentially mediated by adipose TG lipase, hormone-sensitive lipase, and monoacylglycerol lipase.³

IMCL serves as an important energy substrate during muscle contraction.⁴⁰,⁴¹,⁴² Muscles with greater oxidative capacity tend to accumulate higher IMCL content than predominantly glycolytic muscles, a phenomenon termed the “athlete’s paradox.”³³ Therefore, IMCL accumulation per se is not inherently pathogenic; rather, it acts as a precursor pool for lipotoxic intermediates such as long-chain acyl-CoA, diacylglycerol (DAG), and ceramide, which can disrupt insulin signaling (Fig. 2B).⁴⁰,⁴²

A key mechanism underlying the accumulation of these lipotoxic intermediates is mitochondrial dysfunction, which leads to incomplete fatty acid oxidation. This promotes the synthesis of DAG and ceramide.⁴³ Elevated DAG activates specific protein kinase C isoforms, resulting in serine phosphorylation of insulin receptor substrate-1 and subsequent inhibition of insulin signaling.⁴⁴ Ceramide, in contrast, inhibits the Akt/protein kinase B pathway—another central mediator of insulin action.⁴⁵ Additionally, impaired mitochondrial bioenergetics increases reactive oxygen species production, which directly contributes to insulin resistance.⁴⁶

MYOSTEATOSIS AND ATHEROGENIC DYSLIPIDEMIA

In healthy individuals, fatty acids are primarily stored in adipose tissue as triacylglycerol (TAG). However, when adipose tissue expansion reaches its physiological limit, lipid overflow occurs, leading to ectopic TAG accumulation in non-adipose organs such as the liver and skeletal muscle—a process termed ectopic lipid deposition.⁴⁷,⁴⁸,⁴⁹ Within skeletal muscle, both IMAT and IMCL act as potential fatty acid reservoirs that can be mobilized for local metabolic demands. Once within the myocytes, fatty acids undergo either mitochondrial β-oxidation for energy production or are stored as lipid droplets, with smaller fractions incorporated into phospholipid, monoacylglycerol, and DAG pools.³

Conversely, myosteatosis may be associated with metabolic alterations that favor an atherogenic dyslipidemic profile. By exacerbating insulin resistance within skeletal muscle, myosteatosis reduces the capacity for glucose uptake and glycogen synthesis following carbohydrate ingestion. As a result, excess dietary carbohydrates are redirected toward the liver, where hepatic de novo lipogenesis is upregulated.⁴⁸,⁵⁰ This metabolic shift promotes excessive production and secretion of very-low-density lipoprotein (VLDL)-TGs, contributing to the characteristic dyslipidemic pattern of elevated plasma TG and decreased high-density lipoprotein cholesterol (HDL-C).⁴⁸,⁵⁰ Fig. 2C summarizes the bidirectional relationship between myosteatosis and dyslipidemia.

Table 1 summarizes representative studies identified through a targeted literature search (last updated May 6, 2025). This review was conducted as a narrative review. Relevant studies were identified through a targeted PubMed search using predefined keywords related to myosteatosis and lipid metabolism, limited to human studies, followed by manual screening of titles and abstracts for relevance. Overall, studies have consistently demonstrated that greater myosteatosis—reflected by lower skeletal muscle density, greater IMAT area or volume, or higher IMCL content—was associated with an adverse lipid profile, particularly elevated TG⁵¹,⁵³,⁵⁴,⁵⁵,⁵⁷,⁶²,⁶⁶ and reduced HDL-C levels.⁵³,⁵⁴,⁵⁵,⁵⁸,⁶²,⁶⁶ Detailed lipoprotein subfraction analyses further support these associations, showing that elevated levels of VLDL, TG, total cholesterol (TC), phospholipids, and apolipoprotein B, together with lower HDL-C levels, were correlated with larger IMAT area and lower IMAT density.⁶⁵ Notably, when analyses were adjusted for other ectopic fat depots, particularly VAT, the associations between myosteatosis and dyslipidemia were sometimes attenuated or lost,⁵⁵,⁵⁷ suggesting that central obesity may mediate a substantial portion of the observed relationship. Nevertheless, several studies have reported independent associations between myosteatosis and dyslipidemia even after adjustment for visceral fat.⁵²,⁶²,⁶⁹

Table 1. Representative previous studies on myosteatosis and dyslipidemia.

Study	Study design	Study population	Measures of myosteatosis	Lipid	Conclusion
Nakagawa et al. (2007)51	Cross-sectional	47 lean subjects (26 women, 24 young [mean age 21.2], 23 elderly [mean age 70.9])	IMCL concentrations in the tibialis anterior, medial gastrocnemius, and soleus muscles, measured with H-MRS	TG, TC, LDL-C, HDL-C	IMCL content in all skeletal muscles correlated positively with TG, TC, and LDL-C concentrations, but not with HDL-C.
Durheim et al. (2008)52	Longitudinal	73 sedentary, dyslipidemic, overweight subjects who went through 8–9 mon of aerobic exercise (33 women, mean age 50.9 in men, 54.0 in women)	Thigh IMAT change measured with CT at the midpoint of the left thigh	LDL-C particle size, HDL-C particle size	Among overweight men with dyslipidemia, exercise-induced IMAT reduction was inversely correlated with changes in HDL and LDL size, toward larger, less atherogenic lipoproteins. These associations remained after adjusting for VAT. Associations were not significant in women.
Godoy-Matos et al. (2010)53	Cross-sectional	24 non-diabetic obese patients with metabolic syndrome and 9 healthy controls (22 women, mean age 41.5 for metabolic syndrome, 23.0 for control)	IMCL in the soleus muscle, measured with H-MRS	TG, TC, LDL-C, HDL-C	IMCL content was directly associated with TG and inversely with HDL-C. In patients with metabolic syndrome, IMCL was also associated with TC and LDL-C.
Brumbaugh et al. (2012)54	Cross-sectional	441 children from the EPOCH study (226 prepubertal, 215 early pubertal)	IMCL, EMCL in the midcalf area measured with H-MRS	TG, TG/HDL-C ratio	IMCL was associated with the TG/HDL-C ratio and TG levels independent of overall adiposity.
Therkelsen et al. (2013)55	Cross-sectional	2,945 adults from the Framingham Heart Study (50.2% women, mean age 50.8)	Muscle density of the paraspinous muscle measured with abdominal CT	TG, HDL-C	Muscle attenuation was associated with dyslipidemia in both sexes, but stronger in women. After adjustment of BMI or VAT, none of the associations persisted in women; in men, the association between muscle attenuation, low HDL-C, and high TG persisted.
Miljkovic et al. (2013)56	Cross-sectional	1,821 African-Caribbean men from the Tobago health study (mean age 58.9)	Intermuscular adipose tissue area and muscle density measured with calf quantitative CT	TG, LDL-C, HDL-C	In age-adjusted analyses, higher calf muscle density was associated with higher LDL-C and lower HDL-C, but not with TG. Greater intermuscular adipose tissue correlated with lower HDL-C. After further adjustment for age, total body fat, subcutaneous adipose tissue, fasting glucose and insulin, ancestry, and blood pressure, these associations attenuated, and only LDL-C remained independently associated with calf muscle density.
Guglielmi et al. (2014)57	Cross-sectional	32 sedentary patients without cardiovascular disease (14 women, mean age 48.5)	IMAT of erector spinae muscles measured with MRI	TG	IMAT was positively correlated with TG after adjusting for hypolipidemic therapies. However, this association disappeared after further adjusting for waist circumference or intra-abdominal adipose tissue.
Fonvig et al. (2015)58	Cross-sectional	327 Danish children and adolescents, obese vs lean controls (age range 8–18)	IMCL and EMCL in the psoas muscle measured with H-MRS, at the L3 level	TG, TC, LDL-C, HDL-C	In obese or overweight children, higher IMCL content was associated with lower HDL-C. Muscle steatosis (muscle fat content >5%) was not significantly associated with dyslipidemia, but when both hepatic steatosis and muscle steatosis were present, the OR for dyslipidemia increased markedly.
Hioki et al. (2016)59	Cross-sectional	30 physically active adults (15 women, 15 young [mean age 21] and 15 elderly [mean age 71])	IMCL in the vastus lateralis muscle and biceps femoris muscle, measured with H-MRS	Serum free fatty acid levels	IMCL content was significantly correlated with serum free fatty acid levels in the biceps femoris muscle, but not in the vastus lateralis. No significant associations were observed with TG, TC, LDL-C, or HDL-C.
				TG, TC, LDL-C, HDL-C
Kratochvílová et al. (2016)60	Randomized cross-over trial	10 male subjects with impaired fasting glucose (mean age 49.5)	IMCL in the tibialis anterior muscle measured with H-MRS	TG, TC, free fatty acid	After placebo, IMCL correlated negatively with TC. A short telmisartan treatment did not affect IMCL content.
		Treated with 2 wk of telmisartan 160 mg or placebo
Sjöholm et al. (2016)61	Cross-sectional	50 men and 50 women, 50 young (27–31 yr) and 50 elderly (57–61 yr)	IMAT measured with CT, using a multicompartment body composition technique (28 cross-sectional scans)	TC	IMAT was positively associated with serum TC levels in men and younger subjects, independent of BMI.
Lee et al. (2018)62	Cross-sectional	2,529 adults from Framingham Heart Study Offspring and Third Generation (51.9% women, mean age 51.1)	Muscle density of the paraspinous muscle measured with abdominal CT	TG, TC, LDL-C, HDL-C	Intramuscular fat was associated with low HDL-C and high TG (not with TC or high LDL-C) before and after adjusting for BMI. This linear association was not strong enough to significantly predict the presence of clinically defined hypertriglyceridemia (≥150 mg/dL).
Mesinovic et al. (2019)63	Cross-sectional	84 overweight and obese elderly Australian adults (54% women, mean age 63 in subjects with metabolic syndrome, 60.3 with no metabolic syndrome)	Forearm and calf muscle density measured with peripheral quantitative CT	TG, HDL-C	Forearm and calf muscle density were not correlated with TG and HDL-C levels.
Vella et al. (2020)64	Cross-sectional	1,868 adults from the MESA study (50% women, mean age 64.7)	Abdominal muscle density measured with abdominal CT at the L4/5 level	TG, TC, LDL-C, HDL-C, VLDL-C, TC/HDL-C	Total abdominal muscle density showed a positive association with TC but was not related to other lipid parameters. This association was independent of subcutaneous and visceral obesity, as well as other confounders associated with high levels of cholesterol.
Marron et al. (2021)65	Cross-sectional	947 patients of the MESA study (49% women, mean age 63)	Abdominal muscle density and IMAT area, density measured with CT at the L4/5 level	150 lipoprotein subfractions (TC, unesterified cholesterol, phospholipids, TG, apo A-I, apo A-II, and apo B, VLDL, IDL, LDL, HDL)	None of the lipoprotein subfractions were associated with total muscle density. In contrast, higher VLDL, TG, TC, apo-B, and lower HDL-C were associated with higher total abdominal muscle area, higher IMAT area, and lower IMAT density.
			Locomotion muscle (psoas), stabilization muscle (paraspinal, oblique, rectus abdominis)		Some of these associations were strongest among the stabilization muscles, particularly the obliques.
Choi et al. (2022)66	Cross-sectional	35 Korean obese adults divided into MAO and MHO groups (20 women, mean age 44.3 in MAO women, 41.1 in MHO women, 42.5 in MAO men, 48.6 in MHO men)	IMAT volume measured with whole-body MRI	TG, TC, LDL-C, HDL-C	After adjusting for age and sex, serum HDL-C levels showed a negative correlation with IMAT. In women, the MAO group exhibited higher BMI and IMAT, lower HDL-C, and higher TG levels compared with the MHO group. In men, no clear differences were observed across obesity phenotypes.
Hioki et al. (2022)67	Cross-sectional	22 elderly adults (13 women, age range 62–77)	Intramuscular adipose tissue of the vastus lateralis measured with mean echogenic intensity using US	TG, TC, LDL-C, HDL-C, free fatty acid	Echo intensity was significantly inversely correlated with LDL-C and positively correlated with TG.
Kitagawa et al. (2022)68	Cross-sectional	43 healthy Japanese men (23 young, 20 elderly)	IMAT content measured with MRI at the L3 level	TG, TC, LDL-C, HDL-C	Younger group: rectus abdominis IMAT was positively correlated with TC and LDL-C. The average IMAT did not correlate significantly with lipids.
					Older group: average or individual IMAT showed no significant correlation with lipids.
Kim et al. (2024)69	Cross-sectional	11,823 Korean adults, excluding those on lipid-lowering medications (46% women, mean age 53.9 in men, 51.3 in women)	NAMA/TAMA index measured with abdominal CT at the L3 level	TG, TC, LDL-C, HDL-C, apo B/A1, sdLDL-C	A greater NAMA/TAMA index (healthier muscle) was associated with a lower risk of atherogenic dyslipidemia.
					Men: NAMA/TAMA was positively associated with HDL-C and negatively associated with TG, sdLDL-C, and ApoB/A1.
					Women: NAMA/TAMA was positively associated with HDL-C and negatively associated with LDL-C and sdLDL-C.

IMCL, intramyocellular lipid; H-MRS, proton magnetic resonance spectroscopy; TG, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; IMAT, inter- and intramuscular adipose tissue; CT, computed tomography; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VAT, visceral adipose tissue; EMCL, extramyocellular lipid; BMI, body mass index; MRI, magnetic resonance imaging; OR, odds ratio; FFA, free fatty acids; L3, third lumbar vertebral level; US, ultrasound; VLDL-C, very-low-density lipoprotein cholesterol; VLDL, very-low-density lipoprotein; IDL, intermediate-density lipoprotein; Apo A-I, apolipoprotein A-I; Apo A-II, apolipoprotein A-II; Apo B, apolipoprotein B; L4/5, intervertebral level between the fourth and fifth lumbar vertebrae; MAO, metabolically abnormal obese; MHO, metabolically healthy obesity; NAMA, normal attenuation muscle area; TAMA, total abdominal muscle area; sdLDL-C, small dense low-density lipoprotein cholesterol; NAMA/TAMA, normal attenuation muscle area to total abdominal muscle area ratio.

In contrast, associations between myosteatosis and TC or low-density lipoprotein cholesterol (LDL-C) have been more variable: in a multiethnic, population-based cohort, higher CT-measured muscle density was unexpectedly associated with higher TC levels,⁶⁴ contrasting with findings from other studies.⁵¹,⁶¹,⁶⁵ Regarding LDL-C, in a large Korean cohort, myosteatosis quantified by the NAMA/TAMA index was associated with higher odds of elevated LDL-C and small dense LDL-C (sdLDL-C) in women, and sdLDL-C in men.⁶⁹ However, among Afro-Caribbean men, higher calf muscle density—indicative of better muscle quality—was independently associated with higher LDL-C concentrations.⁵⁶

These discrepant findings may partly reflect ethnic differences in genetic predispositions governing fat accumulation, as well as variations in physical activity patterns across populations.⁷⁰,⁷¹ Heterogeneity is further influenced by sex- and age-specific factors, with associations reported predominantly in men in some studies,⁵²,⁶¹ but stronger in women⁵⁵ or younger individuals⁶¹,⁶⁸ in others. These differences may be attributable to sex-specific dynamics of lipolytic enzymes and hormonal shifts following the menopausal transition,⁷²,⁷³ with advancing age further introducing metabolic confounders that may attenuate or obscure the observed relationships. Beyond population-related factors, methodological variability also contributes, including imaging modalities (CT, MRI, H-MRS, US) and the selection of muscle groups (thigh, calf, abdominal, or pelvic muscles). In particular, stabilization muscles enriched in type 1 oxidative fibers inherently contain higher lipid content and tend to exhibit more robust associations with lipid parameters than locomotion muscles.⁶⁴,⁶⁵

Collectively, existing evidence supports a link between myosteatosis and dyslipidemia, particularly elevated TG-rich lipoproteins and reduced HDL-C levels. However, the strength and consistency of these associations vary across studies, reflecting differences in population characteristics, study design, methodological approaches, and confounding by coexisting ectopic fat depots. Given the predominantly cross-sectional nature of the available studies, the directionality and causality of the relationship between myosteatosis and dyslipidemia remain to be clarified.

CLINICAL IMPLICATIONS AND FUTURE CHALLENGES

Individuals with metabolic dysfunction may present with preserved or even increased muscle mass despite impaired muscle quality.²⁶,⁶³,⁶⁹ Importantly, muscle quality and function better reflect adverse clinical outcomes—such as prolonged hospitalization, morbidity, and mortality—than muscle mass alone.⁹,¹⁰,¹¹,¹² Accumulating evidence suggests that myosteatosis is associated with dyslipidemia and serves as a clinically relevant marker of cardiometabolic risk, either independently or synergistically with central adiposity. Therefore, imaging-based evaluation of myosteatosis can complement conventional assessments of muscle mass. From a clinical perspective, incorporating such evaluations into routine risk stratification may help identify individuals with unfavorable metabolic profiles who could benefit from targeted preventive strategies.

Several interventional and longitudinal studies have reported improvements in myosteatosis following weight loss, exercise, and dietary restriction.⁶⁹,⁷⁴,⁷⁵ Pharmacological approaches, such as peroxisome proliferator-activated receptor-γ agonists, glucagon-like peptide-1 (GLP-1) receptor agonist, and dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist have also been explored as potential strategies.⁷⁶,⁷⁷,⁷⁸ In recent randomized clinical trials using MRI-based assessments of thigh muscle fat, liraglutide reduced myosteatosis and improved muscle composition compared with placebo in adults with overweight or obesity.⁷⁴ Similarly, tirzepatide reduced thigh muscle fat infiltration beyond expected weight loss effects in patients with type 2 diabetes, while preserving muscle volume at levels comparable to population-based estimates.⁷⁵ Taken together, these interventional findings reframe myosteatosis from a passive marker of cardiometabolic health to a potentially modifiable therapeutic target.

Despite these advances, several challenges remain. First, standardization of myosteatosis measurement techniques is warranted to establish reference thresholds and enable cross-study comparisons; importantly, such methods should also be feasible for routine clinical implementation. Second, heterogeneous findings in the existing literature highlight the need for further research to clarify how myosteatosis interacts with systemic lipid metabolism. While most interventions improve both myosteatosis and dyslipidemia concurrently, it remains unclear whether improvements in dyslipidemia represent secondary consequences of myosteatosis reduction, whether lipid-lowering therapies can directly ameliorate myosteatosis, or whether myosteatosis improvement itself directly affects dyslipidemia. Given these uncertainties, future prospective studies are needed to determine whether improvements in muscle quality translate into meaningful reductions in cardiometabolic risk.

CONCLUSION

Myosteatosis is increasingly recognized as a metabolically active ectopic adipose depot within skeletal muscle that serves as both an energy reservoir and a source of lipotoxic intermediates, thereby mediating local inflammation and insulin resistance. Accumulating data suggest a bidirectional association between myosteatosis and dyslipidemia: dyslipidemia can promote ectopic fat deposition, while myosteatosis-induced insulin resistance in turn contributes to atherogenic lipid abnormalities. Although such interactions have been observed across diverse populations, the strength and consistency of these associations appear to vary, and their directionality and underlying mechanisms require further investigation.

From a clinical perspective, integrating myosteatosis evaluation into clinical practice may provide a more comprehensive framework for assessing metabolic health by complementing conventional measures of muscle mass. However, further prospective studies are required to determine whether such assessments can meaningfully enhance risk stratification or guide interventions targeting both muscular and systemic metabolic profiles.