This study investigated the effects of Lycium barbarum residues (LBR) and fermented L. barbarum residues (FLBR) on the growth performance and meat quality of lambs. Eighteen lambs were randomly assigned into three groups and fed either a basal diet (CON) or the same diet supplemented with 5.0% LBR or FLBR for a period of 90 days. The underlying mechanisms responsible for the beneficial effect of LBR and FLBR on the longissimus thoracis (LT) and intramuscular fat (IMF) tissues of lambs were examined using multiomics techniques. Our findings showed that FLBR supplementation significantly enhanced the average daily gain, feed efficiency, and nutrient digestibility (P < 0.05 or P < 0.01). Serum total protein (P = 0.007) and glucose (P = 0.002) levels were higher in the FLBR-fed lambs, while urea nitrogen level was lower (P = 0.001). Additionally, the levels of rumen acetate (P = 0.002) and propionate (P = 0.011) were significantly elevated, while ammonia-nitrogen (NH3-N), isobutyrate and isovalerate decreased (P < 0.05 or P < 0.01) following FLBR supplementation. Post-mortem meat quality was also improved by FLBR, as evidenced by enhanced total antioxidant capacity, superoxide dismutase activity, pH, redness (a∗), tenderness and water holding capacity (P < 0.05 or P < 0.01), alongside a reduction in the malonaldehyde content (P < 0.001). Transcriptomic analysis identified 962 differentially expressed genes (DEGs, FLBR vs CON) and 782 DEGs (FLBR vs LBR) in LT, and 1313 DEGs (FLBR vs CON) and 1221 DEGs (FLBR vs LBR) in IMF. The ribosome signaling pathway related genes in LT tissue were activated by the FLBR diet (P < 0.05), showing a higher anabolism of protein. The genes involved in fatty acid biosynthesis in IMF tissue were upregulated by the FLBR diet (P < 0.05), showing a higher anabolism of lipids. Metabolomics analysis identified the 1732 differential metabolites in LT tissue following FLBR supplementation, with significant alterations in metabolites such as carnosine, L-arginine and L-proline, which may serve as potential biomarkers for meat quality betterment. In conclusion, FLBR supplementation might have modified anabolism of proteins and fatty acid, as well as muscle metabolomic profiles, leading to improvements in both growth performance and meat quality in fattening lambs.

We investigated how short-term muscle disuse altered the skeletal muscle metabolome, lipidome, and transcriptome in middle-aged adults. We report that the energy metabolism pathways: nicotinate and nicotinamide metabolism, glycolysis, and TCA cycle, were reduced after 7 days of muscle disuse. These changes in the metabolome were reflected by changes in the transcriptome where multiple genes involved in glycolysis and TCA pathways were reduced after short-term disuse. Phenylalanine, tyrosine, and tryptophan metabolism pathways showed the same response and were reduced after short-term disuse. The skeletal muscle lipidome showed a decrease in phosphatidylinositols but an increase in phosphatidylglycerols and diacylglycerols after short-term muscle disuse. We conclude that short-term muscle disuse in humans has profound and negative effects on the muscle metabolome and lipidome. These include significant downregulation of muscle glycolytic, amino acid, and TCA cycle intermediates. In contrast, skeletal muscle lipids had a divergent response to disuse (e.g., increased phosphatidylglycerols and diacylglycerols, but reduced phosphatidylinositols).NEW & NOTEWORTHY We present the first study that has applied a multiomic analysis (metabolomics, lipidomics, and transcriptomics) of short-term disuse in middle-aged adults. We identified an altered lipidomic and metabolic signature after disuse that included increases in lipids associated with lipotoxicity (e.g., sphingomyelin and diacylglycerol) and reductions in phosphatidylinositol. Energy pathway metabolites for glycolysis and the TCA cycle were reduced after short-term disuse. The lipidomics and metabolomics data were supported by changes in the associated gene expression.

Circadian rhythms are fundamental for regulating physiological processes in organisms, with disruptions often linked to metabolic disorders. This study investigated the role of the roraa gene in zebrafish, particularly its influence on circadian rhythms and metabolic regulation. Using quantitative PCR and in situ hybridization, we confirmed the rhythmic expression of roraa and explored its oscillatory mechanisms. The construction of roraa knockout mutants revealed that the absence of roraa disrupts circadian clock function, as evidenced by the reduced expression of core clock genes and altered behavioral rhythms, while the transgenic zebrafish lines which overexpress roraa just have opposite results. Additionally, we demonstrated that Roraa directly regulates per2 expression through the RORE element in its promoter. Furthermore, the transcriptome analysis and quantitative PCR indicated that the metabolism related genes, especially lipid metabolism related genes were obviously changed in roraa-/- mutants compare with WT. Our findings underscore the critical role of Roraa in coordinating circadian and metabolic processes, providing insights into potential therapeutic targets for addressing metabolic disorders related to circadian disruption.

The carnitine palmitoyltransferases (CPTs) play a key role in controlling the oxidation of long-chain fatty acids and are potential therapeutic targets for diseases with a strong metabolic component, such as obesity, diabetes, and cancer. Four distinct proteins are CPT1A, CPT1B, CPT1C, and CPT2, differing in tissue expression and catalytic activity. CPT1s are finely regulated by malonyl-CoA, a metabolite whose intracellular levels reflect the cell's nutritional state. Although CPT1C does not exhibit significant catalytic activity, it is capable of modulating the functioning of other neuronal proteins. Structurally, all CPTs share a Y-shaped catalytic tunnel that allows the entry of 2 substrates and accommodation of the acyl group in a hydrophobic pocket. Several molecules targeting these enzymes have been described, some showing potential in normalizing blood glucose levels in diabetic patients, and others that, through a central mechanism, are anorexigenic and enhance energy expenditure. However, given the critical roles that CPTs play in certain tissues, such as the heart, liver, and brain, it is essential to fully understand the differences between the various isoforms. We analyze in detail the structure of these proteins, their cellular and physiological functions, and their potential as therapeutic targets in diseases such as obesity, diabetes, and cancer. We also describe drugs identified to date as having inhibitory or activating capabilities for these proteins. This knowledge will support the design of new drugs specific to each isoform, and the development of nanomedicines that can selectively target particular tissues or cells. SIGNIFICANCE STATEMENT: Carnitine palmitoyltransferase (CPT) proteins, as gatekeepers of fatty acid oxidation, have great potential as pharmacological targets to treat metabolic diseases like obesity, diabetes, and cancer. In recent years, significant progress has been made in understanding the 3-dimensional structure of CPTs and their pathophysiological functions. A deeper understanding of the differences between the various CPT family members will enable the design of selective drugs and therapeutic approaches with fewer side effects.

The risk of exercise-induced rhabdomyolysis, followed by abrupt creatine kinase (CK) augmentation, associated with carnitine palmitoyl transferase II (CPTII) deficiency causes patients to abstain from physical training. However, the exercise adjustment to the disease-induced metabolic impairment, accompanied by a tailored nutritional and supplementation strategy, could make sporting activity feasible, even at a competitive level. Here, we report the case of an 18-year-old male basketball player at a competitive level diagnosed for CPTII deficiency after a rhabdomyolytic event. Subsequent genetic analysis revealed the previously unreported c.1741C > T genetic mutation.

The patient underwent a battery of tests to evaluate nutrition (indirect calorimetry; 8-day food records), hydration (bioimpedance analysis), and the use of energy substrates during exercise (cardiopulmonary exercise test, CPET).

Inadequate macronutrients distribution with respect to the reference values for CPTII deficiency, an optimal hydration status, and a non-physiological prevalence of carbohydrates consumption all along the CPET, accentuated with workload augmentation, were found. Based on the results, the patient was provided with a personalized nutritional (carbohydrate = 50-55%, fat = 20%, and protein = 25-30% of total energy) and supplementation (medium-chain triglycerides, β-alanine, and creatine citrate) plan, and indications on the exercise intensity to be adopted to avoid the contribution of fat to energy production. Monitoring of CK for the five months following the resumption of sporting activity shows that the patient no longer had rhabdomyolysis.

These findings suggest that tailoring exercise, nutrition and supplementation upon the disease-induced metabolic limitation makes sport activity at a competitive level feasible in a CPTII-deficient patient, prompting further analysis on larger cohorts.

The prevalence of gestational diabetes mellitus (GDM), a metabolic complication during pregnancy is increasing rapidly. It exerts various short and long term effects on the mother and the child. Nonetheless, the mechanisms underlying the pathophysiology of GDM are still not clear. Placenta is a key 'programming' agent and any impairment in placental structure and function may hamper the fetal growth and development. Omega-3 and omega-6 fatty acids are key nutrients involved in placental and fetal development. The fatty acids transport from maternal circulation towards the fetus depends on the fatty acid status of the mother, fatty acid metabolism of the placenta and placental transport of fatty acids. Alteration in any of these could influence the fatty acids transport towards the fetus thereby affecting the fetal brain development and leading to impairment in cognitive function in the off-spring. We propose a role for placental fatty acid metabolism in influencing fetal growth and development which in turn can have an impact on cognitive development of the offspring born to GDM women.

Selenium-binding protein 1 (SeBP1) is an anticancer factor that affects lipid metabolism in mouse kidneys via the peroxisome proliferator-activated receptor-alpha (PPARA) pathway. However, its physiological role in the liver is difficult to explain because of the presence of the highly homologous selenium-binding protein 2 (SeBP2). To investigate the role of these proteins in the liver, we generated SeBP1 and SeBP2 double-knockout mice (SeBP1/2-DK). SeBP1/2 deletion did not significantly alter the mice phenotypic compared to that of the wild-type strain. Then, we identified the genes involved in hepatic lipid metabolism. The double knockout did not affect fatty acid and cholesterol synthesis, but inhibited fatty acid oxidation and cholesterol efflux. Furthermore, transfection of HepG2 cells with human selenium-binding protein 1 (hSeBP1) positively regulated PPARA and the genes controlled by it. Overexpression of hSeBP1 reduced the levels of non-esterified fatty acids in the culture medium. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different among the three groups. In summary, we elucidated the potential signaling pathways of SeBP1 and SeBP2 in fatty acid oxidation and hepatic cholesterol efflux. Our findings provide insights relevant for developing new strategies to prevent and treat lipid metabolism disorders.

Previous studies demonstrated that Tspo loss causes simple steatosis (SS) in hepatocytes in vitro. However, its effect on SS in vivo remains unclear. In this study, we hypothesise that Tspo loss promotes early-stage MASLD. WT and Tspo KO rats were fed a Gubra Amylin NASH (GAN) diet for 8 weeks to induce SS. Tspo KO rats fed the GAN diet (KO GAN) exhibited increased insulin resistance, higher plasma cholesterol, and elevated hepatic triacylglycerol (TAG) levels, along with higher de novo lipogenesis (DNL) and free fatty acid (FFA) uptake, evidenced by increased fatty acid synthase (FASN) and CD36 expression. The Acyl-coenzyme A binding protein/diazepam-binding inhibitor-TSPO complex facilitated FA transport to the mitochondria, where carnitine palmitoyltransferase 1A (CPT1A) directed them for β-oxidation. TSPO interacted with CPT1A in the outer mitochondrial membrane, while its depletion increased CPT1A expression, boosting FA oxidation. Primary Tspo KO rat hepatocytes and stably overexpressed CD36 (CD36_OE) in Huh7 cells displayed impaired mitochondrial function and compromised mitochondrial membrane potential. KO GAN livers had significantly elevated AcCoA, which acetylated RAPTOR, activating mTORC1 to suppress autophagy. Overall, Tspo deficiency exacerbates the advancement of SS by enhancing CD36-mediated FFA uptake, elevating AcCoA levels, compromising mitochondrial function and impairing autophagy during the early stages of MASLD.

Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism.

To characterize temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol.

Ten healthy adults (9M/1F, [mean ± SD] age 30 ± 10 years; BMI 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours (08:00-08:00 hours). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 22:00 to 07:00 hours. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 hours from 12:00 to 08:00 hours the following day to quantify gene expression.

Plasma insulin displayed diurnal rhythmicity peaking at 18:04 hours. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name, Acrophase [hours]: GLUT4, 14:40; PPARGC1A, 16:13; HK2, 18:24) and lipid metabolism (FABP3, 12:37; PDK4, 05:30; CPT1B, 12:58) displayed 24-hour rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (00:19 hours), nonesterified fatty acids (04:56), glycerol (04:32), triglyceride (23:14), urea (00:46), C-terminal telopeptide (05:07), and cortisol (22:50) concentrations also all displayed diurnal rhythmicity.

Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting.

Oxidative stress may act as a contributing factor in the development of an elevated body mass index (BMI). Oxidative stress has the potential to modulate genetic activity at various levels, including gene transcription and protein function regulation. Nevertheless, the interplay between genetic variants and oxidative stress in relation to BMI remains to be elucidated. Based on this premise, we studied the potential association between 723 single-nucleotide polymorphisms (SNPs) located within a set of 212 genes and both BMI and oxidative stress parameters in 1502 adults from the general Spanish population (Hortega Study). Oxidative stress parameters measured included malondialdehyde (MDA) levels, 8-oxo-2'-deoxyguanosine (8-oxo-dG) levels and oxidised/reduced glutathione ratio (GSSG/GSH). We also examined the potential impact of the interaction between these SNPs and oxidative stress levels on BMI. The genes selected regulate several key biological processes, including obesity, blood pressure, inflammation, lipid metabolism and redox homeostasis. Our findings indicate a robust association between specific genes and both BMI and oxidative stress parameters. Significant BMI-related interactions between genes and oxidative stress parameters were identified, which have a multifactorial impact on oxidative stress modulation and on BMI. SNPs identified in genes such as NPPA, CPT1A, DDIT3, NOX and IL6ST were significantly associated with all oxidative stress parameters analysed, indicating a substantial influence on BMI modulation. The results provide compelling evidence of a significant relationship between oxidative stress levels and genetic background. Our data provide new insights into BMI modulation by oxidative stress levels, highlighting a role for TNF as a key player in the interrelation of oxidative stress and BMI.

This study investigates heterocyclic gamma-butyrobetaine (GBB) analogs as metabolic modulators through an integrated approach involving rational design, molecular docking, synthesis, and in vitro evaluation. The compounds synthesized demonstrated promising inhibitory potential toward carnitine acetyltransferase (CAT) and presumably other enzymes within the carnitine transferase family, with IC50 values ranging from 2.24 to 43.6 mM. Notably, some compounds demonstrated superior activity to the reference drug Meldonium (IC50 = 11.39 mM). A substantial outcome of the study that might serve as a foundation for future optimization and synthesis of more potent compounds was that a bulky, hydrophobic substituent at the gamma position enhances inhibitory activity, whereas esterification and increased polarity diminish it. The most effective compound was determined to be a reversible competitive inhibitor of CAT, with a Ki value of 3.5 mM comparable to Meldonium's Ki of 1.63 mM. These results suggest that heterocyclic GBB analogs present potential candidates for regulating metabolic processes and treating conditions including ischemic diseases, diabetes, and specific cancers.

Gaucher disease (GD), an autosomal recessive lysosomal disorder, primarily affects the lysosomal enzyme β-glucocerebrosidase (GCase), leading to glucosylceramide accumulation in lysosomes. GD presents a wide spectrum of clinical manifestations. This study deploys immune-based proteomics and mass spectrometry-based metabolomics technologies to comprehensively investigate the biochemical landscape in 43 deeply phenotyped type 1 GD patients compared to 59 controls. Conventional and systems biology approaches have been used to analyze the data. The results show promising biological imprints. Elevated phosphatidylcholines in GD patients suggest altered lipid metabolism, potentially due to their increased synthesis. This points to endoplasmic reticulum stress and impaired lipid trafficking, commonly seen in lysosomal diseases. GD patients exhibit an inflammatory profile with elevated cytokines and autoimmune-like inflammation, even in treated patients, highlighting the complexity of GD-related immune imbalances. Mitochondrial dysfunction clues are found through increased oxidative stress markers and altered acylcarnitine profiles in GD patients, suggesting mitochondrial membrane dysfunction affecting carnitine-carrying capacity. Furthermore, platelet count, splenectomy, treatment, and clinical traits were associated with specific omics features, providing insights into GD's clinical heterogeneity and potential diagnostic markers. Autophagy inhibition appears pivotal in GD, driving lipid synthesis, impaired mitochondrial function, and inflammation through chronic activation of mTORC1. Despite limitations like focusing on type 1 GD and using targeted omics approaches, this study provides valuable insights into GD metabolic and immune dysregulation. It lays the basis for future comprehensive investigations into GD manifestations with broader scope and molecular coverage. KEY MESSAGES: The study sheds light on metabolic and immune dysregulation in Gaucher disease. Gaucher disease patients showed elevated phosphatidylcholines, disrupted lipid metabolism, and inflammation profiles. Signs of mitochondrial dysfunction are evident in Gaucher disease patients, with autophagy inhibition significantly affecting lipid synthesis, mitochondrial function, and inflammation via chronic activation of mTORC1.

This review investigates how post-injury cellular signaling and energy metabolism are two pivotal points in zebrafish's cardiomyocyte cell cycle re-entry and proliferation. It seeks to highlight the probable mechanism of action in proliferative cardiomyocytes compared to mammals and identify gaps in the current understanding of metabolic regulation of cardiac regeneration.

Metabolic substrate changes after birth correlate with reduced cardiomyocyte proliferation in mammals. Unlike adult mammalian hearts, zebrafish can regenerate cardiomyocytes by re-entering the cell cycle, characterized by a metabolic switch from oxidative metabolism to increased glycolysis. Zebrafish provide a valuable model for studying metabolic regulation during cell cycle re-entry and cardiac regeneration. Proliferative cardiomyocytes have upregulated Notch, hippo, and Wnt signaling and decreased ROS generation, DNA damage in different zebrafish cardiac regeneration models. Understanding the correlation between metabolic switches during cell cycle re-entry of already differentiated zebrafish cardiomyocytes is being increasingly recognized as a critical factor in heart regeneration. Zebrafish studies provide insights into metabolic adaptations during heart regeneration, emphasizing the importance of a metabolic switch. However, there are mechanistic gaps, and extensive studies are required to aid in formulating therapeutic strategies for cardiac regenerative medicine.

Cadmium (Cd) and polystyrene microplastics (PS-MPs), two ubiquitous environmental contaminants, produce unique synergistic toxicity when co-existing. Key unanswered questions include specific effects on liver function and potential mechanisms.

In this study, C57BL/6 mice and AML12 cells were used to establish in vivo and in vitro models to elucidate the effects of combined exposure to PS-MPs and Cd on the liver and their mechanisms.

The results showed that the combined effects of PS-MPs and Cd caused significantly more liver damage than exposure alone. As observed by transmission electron microscopy (TEM), the number of autophagosomes was significantly increased in the PS-MPs and Cd co-treated group. In addition, autophagic flux was assayed by RFP-GFP-LC3, a reporter system expressing dual fluorescent proteins, which showed an overwhelming enhancement of autophagic flux damage by co-exposure to PS-MPs and Cd compared to exposure alone. To further investigate the involvement of carnitine palmitoyltransferase1(CPT1) in liver injury induced by co-exposure to Cd and PS-MPs, we co-exposed Baicalin, an activator of CPT1, with PS-MPs and Cd, and showed that activation of CPT1 alleviated the impairment of autophagic fluxes induced by co-exposure of Cd and PS-MPs and further alleviated the changes in lipid accumulation and associated protein levels.

In conclusion, the concurrent exposure of PS-MPs and Cd resulted in the blockage of hepatic lipid accumulation and autophagic pathway and further aggravated the toxic damage to the liver. Activation of CPT1 could alleviate the PS-MPs and Cd-induced lipid accumulation and autophagy pathway blockage thus reducing liver injury.

High-magnitude cyclic stretch from arterial blood pressure significantly contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMCs), leading to neointima formation in vein grafts. However, the molecular mechanisms remain unclear. This study highlights the critical role of cytosolic Phospholipase A2 (cPLA2)/ Yin Yang 1 (YY1)/ carnitine palmitoyltransferase 1b (CPT1B) signaling in coordinating VSMC mechanical activation by inhibiting fatty acid β-oxidation. Metabolomic analysis showed that a 15%-1 Hz arterial cyclic stretch, compared to a 5%-1 Hz venous stretch, increased long-chain fatty acids in VSMCs. cPLA2, identified as a mechanoresponsive molecule, produces excessive arachidonic acid (ArAc) under the 15%-1 Hz stretch, inhibiting CPT1B expression, a key enzyme in fatty acid β-oxidation. ArAc promotes transcription factor YY1 degradation, downregulating CPT1B. Inadequate fatty acid oxidation caused by knockdown of CPT1B or YY1, or etomoxir treatment, increased nuclear membrane tension, orchestrating the activation of cPLA2. Overexpressing CPT1B or inhibiting cPLA2 reduced VSMC proliferation and migration in vein grafts, decreasing neointimal hyperplasia. This study uncovers a novel mechanism in lipid metabolic reprogramming in vein grafts, suggesting a new therapeutic target for vein graft hyperplasia.

Succinylation modification involves in the progression of human cancers. The present study aimed to investigate the role of CPT1A, which is a succinyltransferase in the progression of prostate cancer (PCa). CCK-8 was used to detect the cell viability. Seahorse was performed to evaluate the cell glycolysis. Luciferase assay was used to detect the transcriptional regulation. ChIP was performed to assess the binding between transcriptional factors with the promoters. Co-IP was used to assess the binding between proteins. We found that CPT1A was highly expressed in PCa tissues and cell lines. Silencing of CPT1A inhibited the viability and glycolysis of PCa cells. Mechanistically, CPT1A promoted the succinylation of SP5, which strengthened the binding between SP5 and the promoter of PDPK1. SP5 activated PDPK1 transcription and PDPK1 activated the AKT/mTOR signal pathway. These findings might provide novel targets for the diagnosis or therapy of prostate cancer.

Avian migration is among the most energetically demanding feats observed in animals. Studies evaluating the physiological underpinnings of migration have repeatedly shown that migratory birds display numerous adaptations that ultimately supply the flight muscle mitochondria with abundant fuel and oxygen during long-distance flights. To make use of this high input, the organs and mitochondria of migrants are predicted to display several traits that maximize their capacity to produce adenosine triphosphate (ATP). This review aims to introduce readers to several mechanisms by which organs and mitochondria can alter their capacity for oxidative phosphorylation and ATP production. The role of organ size, mitochondrial volume, substrate, and oxygen delivery to the electron transport system are discussed. A central theme of this review is the role of changes in electron chain complex activity, mitochondrial morphology and dynamics, and supercomplexes in allowing avian migrants and other taxa to alter the performance of the electron transport system with predictable shifts in demand. It is my hope that this review will serve as a springboard for future studies exploring the mechanisms that alter bioenergetic capacity across animal species.

The pathophysiology of diabetic cardiomyopathy (DCM) is a phenomenon of great interest, but its clinical problems have not yet been effectively addressed. Recently, the mechanism of ferroptosis in the pathophysiology of various diseases, including DCM, has attracted widespread attention. Here, we explored the role of PACS2 in ferroptosis in DCM through its downregulation of PACS2 expression.

Cardiomyocytes were treated with high glucose and palmitic acid (HGPA), and the detection of cardiomyocyte iron ions, lipid peroxides, and reactive oxygen species (ROS) revealed clear ferroptosis during these treatments. Silencing PACS2 downregulated CPT1A expression and upregulated DHODH expression significantly, reversing HGPA-induced ferroptosis. Further silencing of PACS2 with a CPT1A agonist exacerbated cardiomyocyte ferroptosis while promoting mitochondrial damage in cardiomyocytes. Using a mouse model of type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), we found that PACS2 deletion reversed these treatment-induced increases in cellular iron ions, impaired cardiac function, mitochondrial damage and ferroptosis in cardiac muscle tissues.

The PACS2/CPT1A/DHODH signalling pathway may be involved in ferroptosis in DCM by regulating cardiomyocyte mitochondrial function.

Carnitine palmitoyltransferase II (CPT2) deficiency is a rare genetic disorder that prevents the body from using long-chain fatty acids (LCFAs) for energy. We report a case of a 40-year-old male with a recent episode of rhabdomyolysis triggered by an illness. His liver function tests (LFTs) and creatine kinase (CK) levels were markedly elevated. His rhabdomyolysis improved in the hospital with supportive treatment. At follow-up appointments, it was found that he had labs consistent with CPT2 deficiency. Genetic testing confirmed a homozygous mutation in the CPT2 gene. This report highlights the importance of considering CPT2 deficiency as a cause of recurrent rhabdomyolysis, especially when triggered by non-traumatic causes.

Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid-related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies.

Carnitine Palmitoyl Transferase Type II (CPT II) deficiency is a disorder of fatty acid beta oxidation that causes decreased adenosine triphosphate (ATP) and ketone production during periods of fasting or high energy requirements. Labor and delivery can precipitate attacks for parturients with this disorder, causing hypoglycemia, muscle weakness, rhabdomyolysis, and kidney failure. Anesthetic management considers the delivery mode and anesthetic medications available to reduce these risks. We present the case of a pregnant patient with CPT II deficiency with labor epidural analgesia and a vaginal delivery, with alternative plans had a different delivery mode been required.

Carnitine palmitoyltransferase 1b (Cpt1b) is a crucial rate-limiting enzyme in fatty acid metabolism, but its role and mechanism in early cardiac development remains unclear. Here, we show that cpt1b regulates cardiomyocyte proliferation during zebrafish development. Knocking out entire cpt1b coding sequences leads to impaired cardiomyocyte proliferation, while cardiomyocyte-specific overexpression of cpt1b promotes cardiomyocyte proliferation. RNA sequencing analysis and pharmacological studies identified glutamine synthetase as a key downstream effector of cpt1b in regulating cardiomyocyte proliferation. Our study elucidates a novel mechanism whereby cpt1b promotes zebrafish cardiomyocyte proliferation through glutamine synthetase, which provides new perspectives on the significance of fatty acid metabolism in heart development and the interplay between fatty acid and amino acid metabolic pathways.

Along with abnormalities in glucose metabolism, disturbances in the balance of lipid catabolism and synthesis have emerged as a new area of cancer metabolism that needs to be studied in depth. Disturbances in lipid metabolic homeostasis, represented by fatty acid oxidation (FAO) imbalance, leading to activation of pro-cancer signals and abnormalities in the expression and activity of related metabolically critical rate-limiting enzymes, have become an important part of metabolic remodeling in cancer. The FAO process is a metabolic pathway that facilitates the breakdown of fatty acids into CO2 and H2O and releases large amounts of energy in the body under aerobic conditions. More and more studies have shown that FAO provides an important energy supply for the development of cancer cells. At the same time, the CPT family, including carnitine palmitoyltransferase 1 (CPT1) and carnitine palmitoyltransferase 2 (CPT2), are key rate-limiting enzymes for FAO that exert a pivotal influence on the genesis and progression of neoplastic growth. Therefore, we look at molecular structural properties of the CPT family, the roles they play in tumorigenesis and development, the target drugs, and the possible regulatory roles of CPTs in energy metabolism reprogramming to help understand the current state of CPT family research and to search for new therapeutic strategies.

Significance: Redox stress underlies numerous vascular disease mechanisms. Metabolic adaptability is essential for vascular cells to preserve energy and redox homeostasis. Recent Advances: Single-cell technologies and multiomic studies demonstrate significant metabolic heterogeneity among vascular cells in health and disease. Increasing evidence shows that reductive or oxidative stress can induce metabolic reprogramming of vascular cells. A recent example is intracellular L-2-hydroxyglutarate accumulation in response to hypoxic reductive stress, which attenuates the glucose flux through glycolysis and mitochondrial respiration in pulmonary vascular cells and provides protection against further reductive stress. Critical Issues: Regulation of cellular redox homeostasis is highly compartmentalized and complex. Vascular cells rely on multiple metabolic pathways, but the precise connectivity among these pathways and their regulatory mechanisms is only partially defined. There is also a critical need to understand better the cross-regulatory mechanisms between the redox system and metabolic pathways as perturbations in either systems or their cross talk can be detrimental. Future Directions: Future studies are needed to define further how multiple metabolic pathways are wired in vascular cells individually and as a network of closely intertwined processes given that a perturbation in one metabolic compartment often affects others. There also needs to be a comprehensive understanding of how different types of redox perturbations are sensed by and regulate different cellular metabolic pathways with specific attention to subcellular compartmentalization. Lastly, integration of dynamic changes occurring in multiple metabolic pathways and their cross talk with the redox system is an important goal in this multiomics era. Antioxid. Redox Signal. 41,793-817.

Colorectal cancer (CRC) involves various genetic alterations, with liver metastasis posing a significant clinical challenge. Furthermore, CRC cells mostly show an increase in resistance to traditional treatments like chemotherapy. It is essential to investigate more advanced and effective therapies to prevent medication resistance and metastases and extend patient life. As a result, it is anticipated that small interfering RNAs (siRNAs) would be exceptional instruments that can control gene expression by RNA interference (RNAi). In eukaryotes, RNAi is a biological mechanism that destroys specific messenger RNA (mRNA) molecules, thereby inhibiting gene expression. In the management of CRC, this method of treatment represents a potential therapeutic agent. However, it is important to acknowledge that siRNA therapies have significant issues, such as low serum stability and nonspecific absorption into biological systems. Delivery mechanisms are thus being created to address these issues. In the current work, we address the potential benefits of siRNA therapy and outline the difficulties in treating CRCby focusing on the primary signaling pathways linked to metastasis as well as genes implicated in the multi-drug resistance (MDR) process.

This study investigated the effects of acupuncture and warm acupuncture on the expression and mechanism of the AMP-activated protein kinase (AMPK) signalling pathway associated with lipid accumulation in the liver tissue of rats with metabolic dysfunction-associated fatty liver disease (MAFLD) induced by a high-fat diet. Sprague-Dawley rats were categorised into four groups: control (CON), untreated MAFLD (MAFLD), and two MAFLD groups treated with acupuncture (ACU) and warm acupuncture (WA). The treatment groups underwent 16 application sessions over 8 weeks at the SP9 and BL18 acupoints. We measured the expression levels of AMPK, sterol regulatory element-binding protein1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), peroxisome proliferator-activated receptorα (PPARα), carnitine palmitoyltransferase1 (CPT1), and CPT2. AMPK was activated in both ACU and WA groups. WA downregulated both SREBP1 and ACC expression at the protein level, whereas the acupuncture treatment downregulated SREBP1 expression. Additionally, WA selectively induced the activation of signalling pathways related to AMPK, PPARα, CPT1, and CPT2 at the mRNA level. Histological observations confirmed that fat accumulation was reduced in both the ACU and the WA groups compared to the MAFLD group. The WA treatment-promoted amelioration of HFD-induced MAFLD may be related to the activation of the AMPK/SREBP1/ACC pathway in the liver.

Astaxanthin (Ax) determines the flesh redness of a salmonid fish which is the most desirable quality indicator by consumers. Fish cannot synthesize Ax de novo, therefore, the only way to increase flesh redness is to increase dietary input or improve the absorption and retention rate of dietary Ax. As a hydrophobic carotenoid, the absorption of Ax can be modulated by other lipid molecules in the diet. The present study explored the effect of three lipids, cholesterol (CH), phytosterol (PS), and docosahexaenoic acid (DHA) on Ax absorption, transport, and retention in rainbow trout. Dietary CH significantly improved Ax absorption by elevating plasma Ax levels (p < 0.05); however, it had no effect on the whole body Ax or flesh color. Dietary PS appears to inhibit Ax absorption since fish had significantly (p < 0.05) reduced whole body Ax. Dietary DHA appeared to have no effect on Ax absorption or retention. By comparing intestinal transcriptomes, a low density lipoprotein receptor (ldlr) gene was significantly downregulated in fish fed the CH diet as compared to the control diet. Since LDLR protein plays a major role in plasma lipoprotein turnover, we hypothesized that the inhibition of ldlr gene by high dietary CH resulted in higher retention of plasma Ax. The elevation of plasma Ax was not reflected in higher flesh coloration, which suggested other limiting factors governing Ax retention in the muscle. On the other hand, the transcriptomic and proteomic analyses found no changes of genes or proteins involved in Ax absorption, transport, or excretion in fish fed PS or DHA diets as compared to the control diet. In conclusion, this study has suggested that CH promotes Ax absorption by regulating lipoprotein retention and provide evidence for improving Ax absorption via dietary modulation.

Lead (Pb) is a ubiquitously detected heavy metal pollutant in aquatic ecosystems. Previous studies focused mainly on the response of gut microbiota to Pb stress, with less emphasis on gene expression in intestine, thereby limiting the information about impacts of Pb on intestinal homeostasis in amphibians. Here, microbial community and transcriptional response of intestines in Rana zhenhaiensis tadpoles to Pb exposure were evaluated. Our results showed that 10 μg/L Pb significantly decreased bacterial diversity compared to the controls by the Simpson index. Additionally, 1000 μg/L Pb exposure resulted in a significant reduction in the abundance of Fusobacteriota phylum and Cetobacterium genus but a significant expansion in Hafnia-Obesumbacterium genus. Moreover, transcriptome analysis revealed that about 90 % of the DEGs (8458 out of 9450 DEGs) were down-regulated in 1000 μg/L Pb group, mainly including genes annotated with biological functions in fatty acid degradation, and oxidative phosphorylation, while up-regulated DEGs involved in metabolism of xenobiotics by cytochrome P450. The expression of Gsto1, Gsta5, Gstt4, and Nadph showed strong correlation with the abundance of genera Serratia, Lactococcus, and Hafnia-Obesumbacterium. The findings of this study provide important insights into understanding the influence of Pb on intestinal homeostasis in amphibians.

The carnitine cycle is responsible for the transport of cytoplasmic fatty acids to the mitochondria for subsequent β-oxidation to maintain intracellular energy homeostasis. Recent studies have identified abnormalities in the carnitine cycle in various types of tumors; these abnormalities include the altered expression levels of carnitine cycle-related metabolic enzymes and transport proteins. Dysfunction of the carnitine cycle has been shown to influence tumorigenesis and progression by altering intracellular oxidative and inflammatory status or regulating tumor metabolic flexibility. Many therapeutic strategies targeting the carnitine cycle are actively being explored to modify the dysfunction of the carnitine cycle in patients with malignant tumors; such approaches include carnitine cycle-related enzyme inhibitors and exogenous carnitine supplementation. Therefore, here, we review the studies of carnitine in tumors, aiming to scientifically illustrate the dysfunction of the carnitine cycle in tumor progression and provide new ideas for further research.

The advancement of the Penaeus vannamei industry in a sustainable manner necessitates the creation of eco-friendly and exceptionally effective feed additives. To achieve this, 720 similarly-sized juvenile shrimp (0.88 ± 0.02 g) were randomly divided into four groups in this study, with each group consisting of three replicates, each tank (400 L) containing 60 shrimp. Four experimental diets were formulated by adding 0, 500, 1000, and 1500 mg kg-1 glycerol monolaurate (GML) to the basal diet, and the feeding trial lasted for 42 days. Subsequently, a 72-h White Spot Syndrome Virus (WSSV) challenge test was conducted. Polynomial orthogonal contrasts analysis revealed that with the increase in the concentration of GML, those indicators related to growth, metabolism and immunity, exhibit linear or quadratic correlations (P < 0.05). The results indicate that the GML groups exhibited a significant improvement in the shrimp weight gain rate, specific growth rate, and a reduction in the feed conversion ratio (P < 0.05). Furthermore, the GML groups promoted the lipase activity and reduced lipid content of the shrimp, augmented the expression of triglyceride and fatty acid decomposition-related genes and lowered the levels of plasma triglycerides (P < 0.05). GML can also enhanced the humoral immunity of the shrimp by activating the Toll-like receptor and Immune deficiency immune pathways, improved the phagocytic capacity and antibacterial ability of shrimp hemocytes. The challenge test revealed that GML significantly reduced the mortality of the shrimp compared to control group. The 16S rRNA sequencing indicates that the GML group can increases the abundance of beneficial bacteria. However, 1500 mg kg-1 GML adversely affected the stability of the intestinal microbiota, significantly upregulating intestinal antimicrobial peptide-related genes and tumor necrosis factor-alpha levels (P < 0.05). In summary, 1000 mg kg-1 GML was proven to enhance the growth performance, lipid absorption and metabolism, humoral immune response, and gut microbiota condition of P. vannamei, with no negative physiological effects.

Recurrent miscarriage (RM) has a huge impact on women. Both oxidative stress and ferroptosis play an important role in the pathogenesis of RM. Hence, it was vital to screen the ferroptosis oxidation-related biomarkers for the diagnosis and treatment of RM. We introduced transcript data to screen out differentially expressed genes (DEGs) in RM. Ferroptosis oxidation-related differentially expressed genes were obtained by overlapping DEGs and oxidative stress related genes with correlations >0.9 with ferroptosis-related genes. Least Absolute Shrinkage and Selectionator operator regression and support vector machine based recursive feature elimination algorithm were implemented to screen feature genes. The biomarkers associated with ferroptosis oxidation were screened via receiver operating characteristic curve analysis. We finally analyzed the competing endogenous RNAs regulatory network and potential drugs of biomarkers. We identified 1047 DEGs in RM. Then, 9 ferroptosis oxidation-related differentially expressed genes were obtained via venn diagram. Subsequently, 8 feature genes (PTPN6, GJA1, HMOX1, CPT1A, CREB3L1, SNCA, EPAS1, and TGM2) were identified via machine learning. Moreover, 4 biomarkers associated with ferroptosis oxidation, including PTPN6, GJA1, CPT1A, and CREB3L1, were screened via receiver operating characteristic curve analysis. We constructed the '227 long noncoding RNAs-4 mRNAs-36 microRNAs' network, in which hsa-miR-635 was associated with CREB3L1 and PTPN6. There were 11 drugs with therapeutic potential on 3 biomarkers associated with ferroptosis oxidation. We also observed higher expression of CPT1A and CREB3L1 in RM group compared to the healthy control group by quantitative real-time reverse transcription polymerase chain reaction. Overall, we obtained 4 biomarkers (PTPN6, GJA1, CPT1A, and CREB3L1) associated with ferroptosis and oxidative stress, which laid a theoretical foundation for the diagnosis and treatment of RM.

Kisspeptin signaling regulates energy homeostasis. Adiposity is the principal source and receiver of peripheral Kisspeptin, and adipose Kiss1 metastasis suppressor (Kiss1) gene expression is stimulated by exercise. However, whether the adipose Kiss1 gene regulates energy homeostasis and plays a role in adaptive alterations during prolonged exercise remains unknown. Here, we investigated the role of Kiss1 role in mice and adipose tissues and the adaptive changes it induces after exercise, using adipose-specific Kiss1 knockout (Kiss1adipoq-/-) and adeno-associated virus-induced adipose tissue Kiss1-overexpressing (Kiss1adipoq over) mice. We found that adipose-derived kisspeptin signal regulates lipid and glucose homeostasis to maintain systemic energy homeostasis, but in a sex-dependent manner, with more pronounced metabolic changes in female mice. Kiss1 regulated adaptive alterations of genes and proteins in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OxPhos) pathways in female gWAT following prolonged aerobic exercise. We could further show that adipose Kiss1 deficiency leads to reduced peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) protein content of soleus muscle and maximum oxygen uptake (VO2 max) of female mice after prolonged exercise. Therefore, adipose Kisspeptin may be a novel adipokine that increases organ sensitivity to glucose, lipids, and oxygen following exercise.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure.

Three-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot.

MiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression.

Our findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements.

Currently, there is a lack of effective medicines capable of halting or reversing the progression of neurodegenerative disorders, including amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, or Alzheimer's disease. Given the unmet medical need, it is necessary to reevaluate the existing paradigms of how to target these diseases. When considering neurodegenerative diseases from a systemic neurometabolic perspective, it becomes possible to explain the shared pathological features. This innovative approach presented in this paper draws upon extensive research conducted by the authors and researchers worldwide. In this review, we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases. We provide an overview of the risk factors associated with developing neurodegenerative disorders, including genetic, epigenetic, and environmental factors. Additionally, we examine pathological mechanisms implicated in these diseases such as oxidative stress, accumulation of misfolded proteins, inflammation, demyelination, death of neurons, insulin resistance, dysbiosis, and neurotransmitter disturbances. Finally, we outline a proposal for the restoration of mitochondrial metabolism, a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

Defective fatty acid oxidation (FAO) has been implicated in diabetic kidney disease (DKD), yet little is known about the role of carnitine palmitoyltransferase-1A (CPT1A), a pivotal rate-limiting enzyme of FAO, in the progression of DKD. Here, we investigate whether CPT1A is a reliable therapeutic target for DKD. We first confirmed the downregulation expression of CPT1A in glomeruli from patients with diabetes. We further evaluated the function of CPT1A in diabetic models. Overexpression of CPT1A exhibited protective effects in diabetic conditions, improving albuminuria and glomerular sclerosis as well as mitigating glomerular lipid deposits and podocyte injury in streptozotocin-induced diabetic mice. Mechanistically, CPT1A not only fostered lipid consumption via fatty acid metabolism pathways, thereby reducing lipotoxicity, but also anchored Bcl2 to the mitochondrial membrane, thence preventing cytochrome C release and inhibiting the mitochondrial apoptotic process. Furthermore, a novel transcription factor of CPT1A, FOXA1, was identified. We elucidate the crucial role of CPT1A in mitigating podocyte injury and the progression of DKD, indicating that targeting CPT1A may be a promising avenue for DKD treatment.

A main hepatic consequence of obesity is metabolic-associated fatty liver disease (MAFLD), currently treated by improving eating habits and administrating fibrates yet often yielding suboptimal outcomes. Searching for a new therapeutic approach, we aimed to evaluate the efficacy of hydroxytyrosol linoleoyl ether (HTLE), a dual Ppar-α agonist/Cb1 antagonist with inherent antioxidant properties, as an antisteatotic agent. Using lean and obese Zucker rats, they were administrated daily doses of HTLE (3 mg/kg) over a 15-day period, evaluating its safety profile, pharmacokinetics, impact on body weight, hepatic fat content, expression of key enzymes involved in lipogenesis/fatty acid oxidation, and antioxidant capacity. HTLE decreased the body weight and food intake in both rat genotypes. Biochemical analysis demonstrated a favorable safety profile for HTLE along with decreased concentrations of urea, total cholesterol, and aspartate aminotransferase AST transaminases in plasma. Notably, HTLE exhibited potent antisteatotic effects in obese rats, evidenced by a decrease in liver fat content and downregulation of lipogenesis-related enzymes, alongside increased expression of proteins controlling lipid oxidation. Moreover, HTLE successfully counteracted the redox imbalance associated with MAFLD in obese rats, attenuating lipid peroxidation and replenishing both glutathione levels and the overall antioxidant. Our findings highlight the effectiveness of triple-action strategies in managing MAFLD effectively. Based on our results in the Zucker rat model, HTLE emerges as a promising candidate with triple functionality as an anorexigenic, antisteatotic, and antioxidant agent, offering potential relief from MAFLD symptoms associated with obesity while exhibiting minimal side effects. In conclusion, our study positions HTLE as a highly promising compound for therapeutic intervention in MAFLD treatment, warranting further exploration in clinical trials.

As an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, including palmitoyltransferases and depalmitoylases, and discusses the currently available broad-spectrum and selective inhibitors for these enzymes.

Japanese Brown (JBR) cattle have moderately marbled beef compared to the highly marbled beef of Japanese Black (JBL) cattle; however, their skeletal muscle properties remain poorly characterized. To unveil interbreed metabolic differences over the previous results, we explored the metabolome network changes before and after postmortem 7-day aging in the trapezius muscle of the two cattle breeds by employing a deep and high-coverage metabolomics approach. Using both capillary electrophoresis (CE) and ultra-high-performance liquid chromatography (UHPLC)-Fourier transform mass spectrometry (FT/MS), we detected 522 and 384 annotated peaks, respectively, across all muscle samples. The CE-based results showed that the cattle were clearly separated by breed and postmortem age in multivariate analyses. The metabolism related to glutathione, glycolysis, vitamin K, taurine, and arachidonic acid was enriched with differentially abundant metabolites in aged muscles, in addition to amino acid (AA) metabolisms. The LC-based results showed that the levels of bile-acid-related metabolites, such as tauroursodeoxycholic acid (TUDCA), were high in fresh JBR muscle and that acylcarnitines were enriched in aged JBR muscle, compared to JBL muscle. Postmortem aging resulted in an increase in fatty acids and a decrease in acylcarnitine in the muscles of both cattle breeds. In addition, metabolite set enrichment analysis revealed that JBR muscle was distinctive in metabolisms related to pyruvate, glycerolipid, cardiolipin, and mitochondrial energy production, whereas the metabolisms related to phosphatidylethanolamine, nucleotide triphosphate, and AAs were characteristic of JBL. This suggests that the interbreed differences in postmortem trapezius muscle are associated with carnitine/acylcarnitine transport, β-oxidation, tricarboxylic acid cycle, and mitochondrial membrane stability, in addition to energy substrate and AA metabolisms. These interbreed differences may characterize beef quality traits such as the flavor intensity and oxidative stability.