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PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2026

Intramuscular Fat Infiltration and Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Intramuscular fat infiltration (IMFI) is considered to be closely associated with knee osteoarthritis (KOA); however, its overall association, muscle-specific involvement, and clinical relevance remain unclear. OBJECTIVE: To quantify the association between IMFI and KOA, identify affected muscle groups, and evaluate prognostic value. METHODS: We searched PubMed, Web of Science, Scopus, and Embase up to December 2025 for observational studies. Two reviewers independently screened, extracted data, and assessed bias (NOS/JBI). Pooled standardized mean differences (SMDs) were calculated using random-effects models, with subgroup and sensitivity analyses. RESULTS: Seventeen studies were included. IMFI was significantly higher in KOA patients than controls (SMD = 0.63, 95% CI 0.41-0.85, I2 = 84.7%). Anatomically, the anterior thigh muscles (rectus femoris, vastus lateralis, vastus medialis) demonstrated a significant pooled effect (SMD = 0.96, 95% CI 0.66-1.25, I2 = 3.2%) and showed the strongest pooled association, whereas posterior, medial, and composite measures did not demonstrate significant associations. At the individual muscle level, a single study reported a notable association for the semimembranosus (SMD = 1.25, 95% CI 0.57-1.93); however, this finding is based on limited evidence and requires confirmation in future studies. Subgroup by imaging modality: CT demonstrated a significant association (SMD = 0.59, 95% CI 0.28-0.90), while MRI and ultrasound did not show significant associations. Elevated IMFI was also associated with reduced muscle strength, higher KOA incidence, structural progression, and increased knee replacement risk. CONCLUSION: A moderate positive association exists between IMFI and KOA, with notable muscle-specific heterogeneity. Anterior thigh muscles show the strongest pooled association, whereas individual muscle findings require further confirmation. These findings suggest that IMFI may represent a promising potential marker warranting further prospective investigation for risk stratification, though causality and its role in modifying disease progression remain to be established.

Humans↗

PubMed1975

Effects of long-term administration of alcoholic beverages on the kidney, heart, skeletal muscle and pancreas of rats. A histological study.

No pathological changes in the pancreas, kidneys or skeletal muscle were found in rats maintained for 8 to 9 months with a diet in which alcohol made up 50% of the total calories. An increase of the dietary fat content to 38% did not cause any fatty infiltration of the myocardium.

Alcohol Drinking↗

PubMed1979

Muscle involvement in association with filarial chyluria.

Twenty unselected consecutive patients of filarial chyluria were evaluated clinically, electromyographically, and histopathologically for neuromuscular dysfunction. None of the patients showed clinical evidence of muscle wasting or weakness suggesting myopathy, although generalized muscle weakness was complained by all of them particularly while climbing the stairs or on getting up or during lifting heavy weights. Electromyographic abnormalities were found in nine patients and slight histopathological abnormalities in two. The average duration of motor unit potentials and the mean amplitude were reduced, compatible with myopathy. There were no fibrillation potentials. Histological abnormalities consisted of a marked variation in muscle fibre size, sarcolemmal nuclear proliferation, and mild interstitial fatty infiltration. None of the patients showed evidence of clinical neuropathy, abnormalities in conduction velocity along the nerves or signs of segmental demyelination in the biopsy of the nerve. Our data suggest that muscle weakness in these patients is myopathic in nature without peripheral nerve involvement, and is possible due to hypoproteinaemia and hypolipidaemia, as these patients lose excessive amounts of protein and fat in their urine.

Action Potentials↗

PubMed1975

Congenital generalized lipodystrophy.

Six patients with congenital generalized lipodystrophy are described. They had generalized paucity of fat tissue, acanthosis nigricans, prominent superficial veins and muscle hypertrophy. They were mentally retarded. Three had corneal opacities. They had normal external genitalia and none was tall for age. Their bone age was advanced and some had minor skeletal anomalies and nephromegaly. The muscle histology on light microscopy was normal. The majority had elevated serum aldolase and to a lesser degree serum lactic dehydrogenase and creatinine phosphokinase. Four of five examined had a myopathic electromyogram. They had normal or deranged liver function tests. The fatty liver infiltration in one seems to be progressive. Four had a normal and two an abnormal metyrapone test. They had an age-dependent abnormality of growth hormone, insulin and carbohydrate homeostasis.

Acanthosis Nigricans↗

PubMed1975

[Fatty-acid pattern of human fat and liver tissues in alcoholics and non-alcoholics: fatty-acid pattern as a measure of alcoholism (author's transl)].

Samples from the right lobe of the liver and from fat tissue of the abdominal wall were removed shortly after death from 116 persons. Fatty-acid pattern of both tissues (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic acids) was measured and compared with the degree of fatty infiltration of the liver. The data were also correlated with chronic excess alcohol consumption in the pre-terminal phase. It was found that with increasing fatty inflitration there was a rise in the relative proportion of palmitoleic acid in liver and subcutaneous fat tissues, with a fall in the relative proportion of stearic acid in the latter. Comparison of results in alcoholics (19 subjects) and non-alcoholics (91) showed the expected higher fatty infiltration of the liver in the former (x equal 13.4% and 5.6%, respectively). Both in liver and subcutaneous fat tissues the relative proportion of palmitoleic acid was significantly higher in alcoholics. But while in these the proportion of palmitoleic acid in the liver was higher than in subcutaneous tissue, the relationship was the converse among the non-alcoholics.

Abdominal Muscles↗

PubMed1976

Acetylsecohemicholinium: chemical and pharmacological evaluation of an open-ring hemicholinium.

Acetylsecohemicholinium No. 3 (AcHC-3), the acetate of the open ring (seco form of hemicholinium No. 3, HC-3) hydrolyzes in vitro to the hemiacetal HC-3 at pH values above 9, a temperature-dependent conversion illustrated by ultraviolet spectral shifts from 305 to 257 mmu, and to a limited extent by certain esterases as measured by manometric analysis. An LD50 of 125 mug/kg for a neutral solution of AcHC-3 was decreased to 78.3 mug/kg (the LD50 of HC-3) upon being made basic. Prolonged treatment of mice with LD10-20 doses of AcHC-3 was associated with decreased fatty acid oxidation in the liver and resulted in infiltration of fat into hepatic cells, a reaction preventable by treatment with small doses of choline (10 mg/kg). AcHC-3 causes neuromuscular and autonomic ganglionic blockade, cholinesterase inhibition, and in vitro inhibition of acetylcholine (ACh) synthesis. These actions, although HC-3-like, appear to be due to AcHC-3 rather than HC-3 since neither cholinesterase inhibition nor hepatic ligation altered the neuromuscular blocking actions of AcHC-3. In addition to its HC-3-like properties, AcHC-3 consistently produced a transient increase in twitch height of gastrocnemius muscle before blockade and was dose-responsive in depressing blood pressure and in eliciting contractions of the isolated guinea pig ileum. AcHC-3 is both a cholinomimetic (depresses arterial blood pressure, decreases heart rate and increases ileal contractions) and a competitor of acetylcholine. That is, in most preparations tested, AcHC-3 at lower concentrations has as much intrinsic activity as ACh and at somewhat higher concentrations competitively blocks the responses to ACh. These cholinomimetic actions may be due to the presence of two ACh moieties on the AcHC-3 molecule which attach to cholinergic receptor sites. Also noted was an action of AcHC-3 that seems to be peculiar to the secohemicholiniums, namely, the potentiation of catechloamines.

Acetylcholine↗

PubMed1978

Morphologic effects of dietary plant and animal lipids rich in docosenoic acids on heart and skeletal muscle of cynomolgus monkeys.

Cynomolgi (Macaca fascicularis) were fed diets containing 25% rapeseed oil (RSO), partially hydrogenated herring oil (PHHO), or a 3:1 mixture of lard and corn oil as control for 4 months. The RSO contained approximately 25% of the fatty acids as erucic acid; the PHHO contained a similar concentration of mainly cetoleic acid. The control diet did not include such fatty acids. At the time of necropsy, the RSO- and PHHO-fed monkeys showed myocardial and skeletal muscle lipidosis. Foci of mononuclear cell infiltration, although infrequent, occurred in all three groups and were thought to be nonspecific. The only significant intergroup difference in serum biochemical or hematologic parameters was an increase in serum glutamic-oxaloacetic transaminase activity in both RSO and PHHO groups. Ultrastructural studies confirmed the presence of lipidosis in cardiac and skeletal muscle and revealed mild mitochondrial degeneration, causing a depression of the P/O ratio of the RSO group and a State III respiratory rate depression of the PHHO group. The difference in the exposure/life span ratio represented by this experiment may account for the absence of clear intergroup differences such as are reported in rats used in similar studies, but a true species difference in regard to dietary oils containing docosenoic acids has to be considered as well.

Animals↗

PubMed1978

Effects of plant and animal lipids rich in docosenoic acids on the myocardium of Cynomolgus monkeys.

Cynomolgus monkeys (Macaca fascicularis) were fed diets containing 25% rapeseed oil (RSO), partially-hydrogenated herring oil (PHHO) or a 3:1 mixture of lard/corn oil as control (CON) for 4 months. The RSO contained approximately 25% of the fatty acids as erucic acid (cis-docos-13-enoic, 22:1w9) while the PHHO contained a similar concentration of mainly cetoleic acid (cis-docos-11-enoic, 22:1w11). The CON contained no 22:1 acids. The monkeys developed the expected myocardial lipidosis, somewhat more pronounced in the RSO than the PHHO group, but small foci of mononuclear cell infiltration, while infrequent, occurred in all three groups. Significant intergroup differences in biochemical or hematologic measurements of serum constituents were an increase in serum cholesterol concentration in the RSO group and an increase in serum glutamicoxaloacetic transaminase activity in both RSO and PHHO groups at certain intervals. The shorter proportion of M. fascicularis life span represented by this experiment may account for the absence of clear intergroup differences such as are reported in rats used in similar studies.

Animals↗