The myokine CCL5 recruits subcutaneous preadipocytes and promotes intramuscular fat deposition in obese mice.

Intramuscular fat (IMF) refers to the lipid stored in skeletal muscle tissue. The number and size of intramuscular adipocytes are the primary factors that regulate IMF content. Intramuscular adipocytes can be derived from either in situ or ectopic migration. In this study, it was discovered that the regulation of IMF levels is achieved through the chemokine (C-C motif) ligand 5 (CCL5)/chemokine (C-C motif) receptor 5 (CCR5) pathway by modulating adipocyte migration. In coculture experiments, C2C12 myotubes were more effective in promoting the migration of 3T3-L1 preadipocytes than C2C12 myoblasts, along with increasing CCL5. Correspondingly, overexpressing the CCR5, one of the receptors of CCL5, in 3T3-L1 preadipocytes facilitated their migration. Conversely, the application of the CCL5/CCR5 inhibitor, MARAVIROC (MVC), reduced this migration. In vivo, transplanted experiments of subcutaneous adipose tissue (SCAT) from transgenic mice expressing green fluorescent protein (GFP) provided evidence that injecting recombinant CCL5 (rCCL5) into skeletal muscle promotes the migration of subcutaneous adipocytes to the skeletal muscle. The level of CCL5 in skeletal muscle increased with obesity. Blocking the CCL5/CCR5 axis by MVC inhibited IMF deposition, whereas elevated skeletal muscle CCL5 promoted IMF deposition in obese mice. These results establish a link between the IMF and the CCL5/CCR5 pathway, which could have a potential application for modulating IMF through adipocyte migration.NEW & NOTEWORTHY C2C12 myotubes attract 3T3-L1 preadipocyte migration regulated by the chemokine (C-C motif) ligand 5 (CCL5)/ chemokine (C-C motif) receptor 5 (CCR5) axis. High levels of skeletal muscle-specific CCL5 promote the migration of subcutaneous adipocytes to skeletal muscle and induce the intramuscular fat (IMF) content.

Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle.

BACKGROUND: Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The longissimus dorsi muscle of Dahe pigs (DHM, IMF: 7.98% ± 1.96%) and Dahe black pigs (DHBM, IMF: 3.30% ± 0.64%) was studied to explore cellular heterogeneity and differentially expressed genes (DEGs) associated with IMF deposition using single-nucleus RNA sequencing (snRNA-seq). The lipid composition was then analyzed using non-targeted lipidomics. RESULTS: A total of seven cell subpopulations were identified, including myocytes, fibroblast/fibro/adipogenic progenitors (FAPs), satellite cells, endothelial cells, macrophages, pericytes, and adipocytes. Among them, FAPs and adipocytes were more focused because they could be associated with lipid deposition. 1623 DEGs in the FAPs subpopulation of DHBM were up-regulated compared with DHM, while 1535 were down-regulated. These DEGs enriched in the glycolysis/gluconeogenesis pathway. 109 DEGs were up-regulated and 806 were down-regulated in the adipocyte subpopulation of DHBM compared with DHM, which were mainly enriched in the PPAR signaling pathway and fatty acid (FA) biosynthesis. The expression level of PPARG, ABP4, LEP, and ACSL1 genes in DHM was higher than that in DHBM. Lipidomics reveals porcine lipid composition characteristics of muscle tissue. A total of 41 lipid classes and 2699 lipid species were identified in DHM and DHBM groups. The top ten relative peak areas of lipid classes in DHM and DHBM were triglyceride (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), diglyceride (DG), cardiolipin (CL), ceramides (Cer), Simple Glc series (Hex1Cer), sphingomyelin (phSM), and phosphatidylinositol (PI). The relative peak areas of 35 lipid species in DHM were lower than DHBM, and 28 lipid species that were higher. There was a significant increase in the TG fatty acyl chains C6:0, C17:0, and C11:4, and a significant decrease in C16:0, C18:1, C18:2, and C22:4 in DHBM (p < 0.05). CONCLUSIONS: C16:0 FA may downregulate the expression level of PPARG gene, which leads to the downregulation of fat metabolism-related genes such as ACSL, PLIN2, and FABP4 in DHBM compared with DHM. This may be the reason that the lipid deposition ability of Dahe pigs is stronger than that of Dahe black pigs, which need further investigation.

RNA sequencing identifies key genes involved in intramuscular fat deposition in chickens at different developmental stages.

BACKGROUND: Intramuscular fat (IMF) is an important factor in meat quality, and triglyceride (TG) and Phospholipids (PLIP), as the main components of IMF, are of great significance to the improvement of meat quality. RESULTS: In this study, we used 30 RNA sequences generated from the transcriptome of chicken breast muscle tissues at different developmental stages to construct a gene expression matrix to map RNA sequence reads to the chicken genome and identify the transcript of origin. We used weighted gene co-expression network analysis (WGCNA) and identified 27 co-expression modules, 10 of which were related to TG and PLIP. We identified 150 highly-connected hub genes related to TG and PLIP, respectively, which were found to be mainly enriched in the adipocytokine signaling pathway, MAPK signaling pathway, mTOR signaling pathway, FoxO signaling pathway, and TGF-beta signaling pathway. Additionally, using the BioMart database, we identified 134 and 145 candidate genes related to fat development in the TG-related module and PLIP-related module, respectively. Among them, RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 were identified as candidate genes related to fat development and highly-connected hub genes in the module, suggesting that these ten genes may be important candidate genes affecting IMF deposition. CONCLUSIONS: RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 may be important candidate genes affecting IMF deposition. The purpose of this study was to identify the co-expressed gene modules related to chicken IMF deposition using WGCNA and determine key genes related to IMF deposition, so as to lay a foundation for further research on the molecular regulation mechanism underlying chicken fat deposition.

Preliminary studies on the molecular mechanism of intramuscular fat deposition in the longest dorsal muscle of sheep.

BACKGROUND: Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry intramuscular fat content is influenced by genetics, nutritional level, and environmental factors. Key regulatory factors play a crucial role in intramuscular fat deposition. However, there is a limited amount of research on the identification and function of key genes involved in intramuscular fat content deposition specifically in sheep. RESULTS: Histological differences in the longest dorsal muscle of the small-tailed frigid sheep increased in diameter and decreased in several muscle fibers with increasing monthly age; The intramuscular fat content of the longest dorsal muscle of the small-tailed cold sheep varied with age, with a minimum of 1 month of age, a maximum of 6 months of age, and a minimum of 12 months of age. Transcriptomic sequencing and bioinformatics analysis revealed a large number of differential genes in the longest dorsal muscles of little-tailed billy goats of different months of age, which were enriched in multiple GO entries and KEGG pathways. Among them, the pathway associated with intramuscular fat was the AMPK signaling pathway, and the related genes were PPARGC1A and ADIPOQ; Immunohistochemical studies showed that PPARGC1A and ADIPOQ proteins were expressed in connective tissues, cell membranes, and, to a lesser extent, the cytoplasm of the longest dorsal muscle of the little-tailed frigid sheep; Real-time PCR and Western Blot validation showed that PPARGC1A and ADIPOQ were both expressed in the longest dorsal muscle of the little-tailed frigid sheep at different ages, and there were age differences in the amount of expression. The ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle, and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle; As inferred from the above results, the ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle (r = -0.793, P < 0.05); and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle r = 0.923, P < 0.05). CONCLUSIONS: Based on the above results, it can be inferred that the ADIPOQ gene is negatively correlated with the intramuscular fat content of the longest back muscle (r = -0.793, P < 0.05); the PPARGC1A gene is positively correlated with the intramuscular fat content of the longest back muscle (r = 0.923, P < 0.05).

CircSSBP2 acts as a MiR-2400 sponge to promote intramuscular preadipocyte proliferation by regulating NDRG1.

Intramuscular fat (IMF) is a critical factor in beef quality. IMF is mainly distributed between muscle fibres and its accumulation can affect the marbling and meat quality of beef. IMF formation and deposition is a complex process and in recent years a group of non-coding RNAs (ncRNAs), known as circRNAs, have been discovered to play an important role in regulating intramuscular fat deposition. CircRNAs form a covalent loop structure after reverse splicing of precursor mRNAs. They can act by adsorbing miRNAs, thereby reducing their repressive effects on downstream target genes. Based on high-throughput sequencing of circRNAs in intramuscular fat of Qinchuan and Japanese black cattle, we identified a novel circSSBP2 that is differentially expressed between the two species and associated with adipogenesis. We show that circSSBP2 knockdown promotes bovine intramuscular preadipocyte proliferation, whereas overexpression inhibits bovine intramuscular preadipocyte proliferation. We also show that circSSBP2 can act as a molecular sponge for miR-2400 and that miR-2400 overexpression promotes bovine intramuscular preadipocyte proliferation. Furthermore, N-myc downstream-regulated gene 1 (NDRG1) was identified as a direct target gene of miR-2400, and NDRG1 interference promoted the proliferation of bovine intramuscular preadipocytes. In conclusion, our results suggest that circSSBP2 inhibits the proliferation of bovine intramuscular preadipocytes by regulating the miR-2400/NDRG1 axis.

Semi-quantitative thigh magnetic resonance imaging scores in assessing disease activity and determining long-term clinical outcome in idiopathic inflammatory myopathies: a causal mediation analysis.

OBJECTIVES: To evaluate the relationship of thigh MRI (t-MRI) with manual muscle testing-8 (MMT-8), muscle enzymes and autoantibodies. To determine the causal and mediating factors resulting in poor recovery of MMT-8 in inflammatory myositis (IIM). METHODS: This was a single-centre retrospective study in IIM patients. t-MRI was semi-quantitatively scored for muscle oedema, fascial oedema, muscle atrophy and fatty infiltration. Spearman correlation of t-MRI scores was done with muscle enzymes at baseline, and MMT-8 at baseline and on follow-up. Causal mediation analysis was performed with age, sex, symptom duration, autoantibodies, diabetes and BMI as independent variables, follow-up MMT-8 as dependent and t-MRI scores as mediating variables. RESULTS: Baseline evaluation was done on 59 and follow-up on 38 patients. Median follow-up of the cohort was 31 (10-57) months. Baseline MMT-8 negatively correlated with muscle oedema (r = -0755), fascial oedema (r = -0.443) and muscle atrophy (r = -0.343). Creatinine kinase (r = 0.422) and aspartate transaminase (r = 0.480) positively correlated with muscle oedema. Follow-up MMT-8 correlated negatively with baseline atrophy (r = -0.497) and fatty infiltration (r = -0.531). On follow-up, MMT-8 males had positive total effect (estimate (95%CI)) via atrophy [2.93 (0.44, 4.89)] and fatty infiltration [2.08 (0.54, 3.71)]. Antisynthetase antibody had a positive total effect via fatty infiltration [4.50 (0.37, 7.59)]. Age had a negative total effect via atrophy [-0.09 (0.19, -0.01)] and fatty infiltration [-0.07 (-0.15, -0.01)]. Disease duration had a negative total effect via fatty infiltration [-0.18 (-0.27, -0.02)]. CONCLUSION: Baseline fatty infiltration and muscle atrophy resulting from older age, female sex, longer disease duration and absent anti-synthetase antibodies, partly mediate muscle recovery in IIM.

A multifaceted and inclusive methodology for the detection of sarcopenia in patients undergoing bariatric surgery: an in-depth analysis of current evidence.

Bariatric surgery is widely recognized as the most effective intervention for obesity and offers benefits beyond weight loss. However, not all patients achieve satisfactory weight loss, balanced changes in body composition, and resolution of comorbidities. Therefore, thorough pre- and postoperative evaluations are important to predict success and minimize adverse effects. More comprehensive assessments require broadening the focus beyond body weight and fat measurements to consider quantitative and qualitative evaluations of muscles. Introducing the concept of sarcopenia is useful for assessing the degradative and pathological changes in muscles associated with cardiometabolic function, physical performance, and other obesity-related comorbidities in patients undergoing bariatric surgery. However, there is currently no consensus or definition regarding the research and clinical use of sarcopenia in patients undergoing bariatric surgery. Therefore, this review aimed to define the concept of sarcopenia applicable to patients undergoing bariatric surgery, based on the consensus reached for sarcopenia in the general population. We also discuss the methods and significance of measuring muscle mass, quality, and strength, which are key variables requiring a comprehensive assessment.

Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients.

BACKGROUND: In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS: This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS: The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.

Muscle biopsy long-chain omega-3 polyunsaturated fatty acid compositions, IMF and FMP in Australian pasture-based Bowen Genetics Forest Pastoral Angus, Hereford, and Wagyu Beef Cattle.

BACKGROUND: We investigated breed and gender variations in the compositions of long-chain (≥ C20) omega-3 polyunsaturated fatty acids (LC omega-3 PUFA), fat melting point (FMP) and intramuscular fat (IMF) contents in biopsy samples of the M. longissimus dorsi muscle of grazing beef cattle. The hypothesis that biopsy compositions of health-beneficial LC omega-3 PUFA, FMP and IMF in a pasture-based production system will vary with breed, was tested. Muscle biopsies were taken from 127 yearling pasture-based Angus, Hereford, and Wagyu heifers and young bulls exclusive to the Australian Bowen Genetics Forest Pastoral breeding stud averaging 12 ± 2.43 months of age and under the same management routine. RESULTS: Breed had a significant influence on IMF, FMP, and the compositions of oleic acid, α-linolenic acid (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA), docosapentaenoic (DPA), and total EPA + DHA + DPA in the M. longissimus dorsi muscle biopsies (P ≤ 0.03). The Wagyu breed had the highest (11.1%) and Hereford the lowest (5.9%) IMF (P = 0.03). The reverse trend was observed in FMP values where the Hereford breed had the highest (55 °C), Angus intermediate (46.5 °C), and Wagyu the lowest (33 °C) FMP. The Wagyu and Angus breeds had similar oleic fatty acid (18:1n-9) content, while the Hereford breed had the lowest (P < 0.01). The highest ALA, DPA, total EPA + DHA, total EPA + DHA + DPA and total ALA + EPA + DHA + DPA contents were detected in the Wagyu breed (P ≤ 0.03). The Hereford had similar EPA and DPA contents to the Angus (P ≥ 0.46). Total EPA + DHA + DPA contents in Wagyu, Angus, and Hereford were 28.8, 21.5, and 22.1 mg/100g tissue (P = 0.01), respectively. Sex was an important source of variation that influenced LC omega-3 PUFA composition, FMP and IMF, where yearling heifers had higher IMF (11.9% vs 5.3%), lower FMP (33°C vs 37°C), and higher LC omega-3 PUFA than bulls. CONCLUSION: All the results taken together indicate that the Wagyu breed at 28.8 mg/100g tissue, was the closest to meeting the Australia and New Zealand recommended source level threshold of 30 mg/100g tissue of health-beneficial ≥ C20 omega-3 FA content. Since gender was a significant determinant of LC omega-3 PUFA composition, IMF content and FMP, it should be factored into enhancement strategies of healthy meat eating quality traits in grazing cattle. These findings also suggest that the Bowen Genetics Forest Pastoral beef cattle studs are important sources of LC omega-3 PUFA that can be used to cover the deficit in these health claimable fatty acids in Western diets.

Integrated analysis of differently expressed microRNAs and mRNAs at different postnatal stages reveals intramuscular fat deposition regulation in goats (Capra hircus).

Intramuscular fat refers to the adipose tissue distributed in the muscle. It is an important indicator that affects the quality of goat meat, and can directly affect the tenderness and flavor of goat meat. Our previous study revealed the mRNA that may be crucial for intramuscular fat deposition during goat growth; however, how the microRNAs (miRNAs) are involved in the process is largely unclear. In the present study, a total of 401 known miRNAs and 120 goat novel miRNAs, including 110 differentially expressed (DE) miRNAs, were identified among longissimus dorsi from three growth stages (2, 9, and 24 months) by miRNA sequencing. Combining analysis of the DE mRNAs and DE miRNAs was then performed by miRDB and miRwalk, and miR-145-5p and FOXO1, miR-487b-3p, and PPARG coactivator 1 α (PPARGC1A), miR-345-3p, and solute carrier family 2 member 4 (SLC2A4), etc. were shown to closely associate with lipid metabolism, which was then validated by a correlation analysis. The final DE mRNAs were significantly enriched in fatty acid transmembrane transport, fatty acid homeostasis, apelin signaling pathway, glucagon signaling pathway, insulin signaling pathway, and AMPK signaling pathway by gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Besides, miR-145-5p showed a certain effect on goat intramuscular fat metabolism by acting on the possible target gene Forkhead Box O1 (FOXO1). These data provide some theoretical support for improving the quality of goat meat.

Smartphone-based digital phenotyping for genome-wide association study of intramuscular fat traits in longissimus dorsi muscle of pigs.

Intramuscular fat (IMF) content and distribution significantly contribute to the eating quality of pork. However, the current methods used for measuring these traits are complex, time-consuming and costly. To simplify the measurement process, this study developed a smartphone application (App) called Pork IMF. This App serves as a rapid and portable phenotyping tool for acquiring pork images and extracting the image-based IMF traits through embedded deep-learning algorithms. Utilizing this App, we collected the IMF traits of the longissimus dorsi muscle in a crossbred population of Large White × Tongcheng pigs. Genome-wide association studies detected 13 and 16 SNPs that were significantly associated with IMF content and distribution, respectively, highlighting NR2F2, MCTP2, MTLN, ST3GAL5, NDUFAB1 and PID1 as candidate genes. Our research introduces a user-friendly digital phenotyping technology for quantifying IMF traits and suggests candidate genes and SNPs for genetic improvement of IMF traits in pigs.

Sarcopenia and Ageing.

Musculoskeletal ageing is a major health challenge as muscles and bones constitute around 55-60% of body weight. Ageing muscles will result in sarcopenia that is characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes. In recent years, a few consensus panels provide new definitions for sarcopenia. It was officially recognized as a disease in 2016 with an ICD-10-CM disease code, M62.84, in the International Classification of Diseases (ICD). With the new definitions, there are many studies emerging to investigate the pathogenesis of sarcopenia, exploring new interventions to treat sarcopenia and evaluating the efficacy of combination treatments for sarcopenia. The scope of this chapter is to summarize and appraise the evidence in terms of (1) clinical signs, symptoms, screening, and diagnosis, (2) pathogenesis of sarcopenia with emphasis on mitochondrial dysfunction, intramuscular fat infiltration and neuromuscular junction deterioration, and (3) current treatments with regard to physical exercises and nutritional supplement.

A review of emerging technologies, nutritional practices, and management strategies to improve intramuscular fat composition in beef cattle.

The flavour, tenderness and juiciness of the beef are all impacted by the composition of the intramuscular fat (IMF), which is a key determinant of beef quality. Thus, enhancing the IMF composition of beef cattle has become a major area of research. Consequently, the aim of this paper was to provide insight and synthesis into the emerging technologies, nutritional practices and management strategies to improve IMF composition in beef cattle. This review paper examined the current knowledge of management techniques and nutritional approaches relevant to cattle farming in the beef industry. It includes a thorough investigation of animal handling, weaning age, castration, breed selection, sex determination, environmental factors, grazing methods, slaughter weight and age. Additionally, it rigorously explored dietary energy levels and optimization of fatty acid profiles, as well as the use of feed additives and hormone implant techniques with their associated regulations. The paper also delved into emerging technologies that are shaping future beef production, such as genomic selection methods, genome editing techniques, epigenomic analyses, microbiome manipulation strategies, transcriptomic profiling approaches and metabolomics analyses. In conclusion, a holistic approach combining genomic, nutritional and management strategies is imperative for achieving targeted IMF content and ensuring high-quality beef production.

Association of mid-thigh quadriceps muscle quality with postoperative outcomes in patients with hip osteoarthritis undergoing total hip arthroplasty: a retrospective cohort study.

PURPOSE: Muscle quality is more important than muscle mass for assessing physical function. Computed tomography (CT) is used to evaluate intramuscular fatty infiltration. The mid-thigh quadriceps CT attenuation values (CTV) expressed in Hounsfield units (HU) negatively correlate with physical function. Patients with hip osteoarthritis (HOA) have lower extremity muscle atrophy, including decreased cross-sectional area (CSA), CTV, and muscle strength. Using preoperative CT images, we investigated the association between mid-thigh quadriceps CSA, CTV, and postoperative outcomes in patients with HOA. METHODS: This study included 62 patients who had unilateral HOA (62 hips) and underwent total hip arthroplasty (THA). We investigated the association between preoperative and postoperative Japanese Orthopaedic Association (JOA) hip scores, 12-item Short Form survey (SF-12), mid-thigh quadriceps CSA, and CTV. RESULTS: The mean age was 64.7 ± 10.1 years, with 15 men (24.2%), and the mean body mass index was 24.3 ± 4.3 kg/m2. Secondary HOA was present in 79.0% of patients. The mean CSA and CTV of the mid-thigh quadriceps on the operative side were 38.8 ± 9.8 cm2 and 40.3 ± 7.8 HU, respectively. Multiple regression analyses adjusted for age and sex showed that preoperative mid-thigh quadriceps CSA was not associated with preoperative and postoperative JOA hip scores or SF-12. The preoperative mid-thigh quadriceps CTV was associated with the postoperative JOA hip score in the gait ability domain and SF-12 in the physical component summary domain. CONCLUSION: Preoperative muscle quality is associated with postoperative outcomes in patients who have HOA regardless of age and sex.

Molecular and Cellular Mechanisms of Intramuscular Fat Development and Growth in Cattle.

Intramuscular fat, also referred to as marbling fat, is the white fat deposited within skeletal muscle tissue. The content of intramuscular fat in the skeletal muscle, particularly the longissimus dorsi muscle, of cattle is a critical determinant of beef quality and value. In this review, we summarize the process of intramuscular fat development and growth, the factors that affect this process, and the molecular and epigenetic mechanisms that mediate this process in cattle. Compared to other species, cattle have a remarkable ability to accumulate intramuscular fat, partly attributed to the abundance of sources of fatty acids for synthesizing triglycerides. Compared to other adipose depots such as subcutaneous fat, intramuscular fat develops later and grows more slowly. The commitment and differentiation of adipose precursor cells into adipocytes as well as the maturation of adipocytes are crucial steps in intramuscular fat development and growth in cattle. Each of these steps is controlled by various factors, underscoring the complexity of the regulatory network governing adipogenesis in the skeletal muscle. These factors include genetics, epigenetics, nutrition (including maternal nutrition), rumen microbiome, vitamins, hormones, weaning age, slaughter age, slaughter weight, and stress. Many of these factors seem to affect intramuscular fat deposition through the transcriptional or epigenetic regulation of genes directly involved in the development and growth of intramuscular fat. A better understanding of the molecular and cellular mechanisms by which intramuscular fat develops and grows in cattle will help us develop more effective strategies to optimize intramuscular fat deposition in cattle, thereby maximizing the quality and value of beef meat.

Gga-let-7a-3p inhibits the proliferation and differentiation of chicken intramuscular preadipocytes.

1. Intramuscular fat (IMF) is a key parameter for chicken meat quality. IMF deposition is driven by genetic, nutritional and management factors, with genetics being the determining factor. Previous whole transcriptome sequencing revealed that microRNA gga-let-7a-3p was related to lipid metabolism in breast muscle. This study further investigated the potential role of gga-let-7a-3p in IMF deposition.2. The mimic and inhibitor of gga-let-7a-3p were individually transfected into chicken intramuscular preadipocytes. Subsequently, the proliferation and differentiation states of the cells were detected. Transcriptome sequencing was performed on cells transfected with gga-let-7a-3p mimic.3. The results indicated that gga-let-7a-3p suppressed the mRNA levels of proliferation and differentiation-related genes, as well as the protein levels. EdU and Oil Red O assays revealed that gga-let-7a-3p restrained preadipocyte proliferation and differentiation. In addition, a total of 333 up-regulated genes and 807 down-regulated genes were identified in cells transfected with gga-let-7a-3p mimic. Using Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, differential genes were found to be enriched in processes such as the peroxisome proliferator activated receptor (PPAR) signalling pathway and oxidative phosphorylation.4. The study demonstrated that gga-let-7a-3p inhibits the proliferation and differentiation of chicken intramuscular preadipocytes, which provides new understanding to further unravel the function of gga-let-7a-3p.

Profiling and functional analysis of circular RNAs in yaks intramuscular fat.

Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression. However, the regulatory mechanisms of lipid metabolism in yaks involved in circRNAs remain poorly understood. The IMF plays a crucial role in the quality of yak meat, to greatly improve the meat quality. In this study, the fatty acid profiles of yak IMF were determined and circRNAs were sequenced. The results showed that the total of polyunsaturated fatty acid (PUFA) content of adult yak muscle was significantly higher than that in yak calves (p < 0.05). A total of 29,021 circRNAs were identified in IMF tissue, notably, 99 differentially expressed (DE) circRNAs were identified, to be associated with fat deposition, the most significant of which were circ_12686, circ_6918, circ_3582, ci_106 and ci_123 (A circRNA composed of exons is labelled 'circRNA' and a circRNA composed of introns is labelled 'ciRNA'). KEGG pathway enrichment analysis showed that the differential circRNAs were enriched in four pathways associated with fat deposition (e.g., the peroxisome proliferator-activated receptor signalling, fatty acid degradation, sphingolipid metabolism and sphingolipid signalling pathways). We also constructed co-expression networks of DE circRNA-miRNA using high-throughput sequencing in IMF deposition, from which revealed that ci_106 target binding of bta-miR-130b, bta-miR-148a, bta-miR-15a, bta-miR-34a, bta-miR-130a, bta-miR-17-5p and ci_123 target binding of bta-miR-150 were involved in adipogenesis. The study revealed the role of the circRNAs in the IMF deposition in yak and its influence on meat quality the findings demonstrated the circRNA differences in the development of IMF with the increase of age, thus providing a theoretical basis for further research on the molecular mechanism of IMF deposition in yaks.

Integrated multi-omics analysis reveals variation in intramuscular fat among muscle locations of Qinchuan cattle.

BACKGROUND: Intramuscular fat (IMF) is closely related to the tenderness, marbling, juiciness, and flavor of meat. We used a combined transcriptome and metabolome analysis to investigate the molecular mechanisms underlying phenotypic variation among Qinchuan cattle. RESULTS: The IMF content was relatively high in the meat of Qinchuan cattle bulls and differed among muscle locations, namely the high rib (15.86%), ribeye (14%), striploin (10.44%), and tenderloin (8.67%). CCDC80 and the HOX gene cluster may regulate intramuscular adipose tissue deposition. Moreover, erucic acid (EA) was found to be the main metabolite in Qinchuan beef cattle, with a high concentration in IMF. The deposition of IMF could be regulated by the metabolic pathway for unsaturated fatty acids involving EA and the ACOX3, HACD2, and SCD5 genes. In addition, differentially expressed genes and metabolites were enriched in three major KEGG pathways: purine metabolism, pyrimidine metabolism, and the metabolism of glycine, serine, and threonine. CONCLUSIONS: We identified a significant metabolite, EA, with variation in IMF. Its closely related genes, ACOX3, HACD2, and SCD5, co-regulate the metabolism of unsaturated fatty acids, ultimately affecting the accumulation of intramuscular adipose tissue in Qinchuan cattle. Consequently, Qinchuan cattle are an elite cultivar for high-quality beef production and have great potential for breeding.

A Comparative Study on the Carcass and Meat Chemical Composition, and Lipid-Metabolism-Related Gene Expression in Korean Hanwoo and Brindle Chikso Cattle.

The objective of this study was to elucidate the effect of cattle breed on carcass and meat chemical composition, fatty acid profiles, and lipid-metabolism-related genes. For this study, same-age Hanwoo and Chikso steers (n = 6 per breed) reared under identical conditions were used. Immediately after slaughter, muscle tissues were collected for analysis of mRNA expression. At 24 h post-mortem, the carcasses were assessed for carcass traits (marbling score, meat yield, etc.), and meat quality and fatty acid profiles in the longissimus lumborum (LL) and semimembranosus (SM) muscles. The results showed that no differences in the slaughter weight, dressing rate, back-fat thickness, trimmed fat, and total meat yield occurred between the two breeds (p > 0.05). However, Hanwoo cattle had a higher marbling score, intramuscular fat (IMF) content, and expression level of lipid-metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor gamma, and fatty acid binding protein 4, compared with Chikso (p < 0.05). Contrastingly, Chikso had a higher total unsaturated fatty acid content and expression level of stearoyl CoA desaturase 1 (p < 0.05). It may be said that the difference in the expression levels of lipid-metabolism-related genes could be the molecular factors underlying IMF deposition and fatty acid profile differences in the beef from the two breeds.

Vitamin K3 promotes CCL5 expression to recruit preadipocytes deposition to skeletal muscle.

Intramuscular fat (IMF), also known as ectopic fat deposits in skeletal muscle. Researches of IMF mainly focus on increasing the number and size of intramuscular adipocytes in situ. However, recent studies have shown that chemokines secreted by skeletal muscle recruit adipocytes to increase intramuscular fat content. Chemokine ligand 5 (CCL5), a member of chemokine family, is involved in the regulation of cell migration, inflammatory responses, and energy metabolism. In this study, we determined Vitamin K3 (VK3) enhanced Ccl5 transcription and expression, thus resulting in increased preadipocyte migration. VK3-injected vastus lateralis (VL) was observed an increased CCL5 concentration and IMF deposition, whereas blockade of the CCL5/CCR5 axis decreased IMF deposition.VK3 treatment also increased the body weight and VL ratio in mice. In summary, VK3, which targets CCL5, is expected to be a novel pharmacological regulator for promoting IMF content.