Metabolites

3 pages, 128 KB

Open AccessEditorial

Effects of Environmental Exposure on Host and Microbial Metabolism

by Bei Gao and Pengcheng Tu

Metabolites 2025, 15(10), 646; https://doi.org/10.3390/metabo15100646 - 26 Sep 2025

Trillions of microorganisms are living in our gastrointestinal tract, known as the gut microbiota, which plays an essential role in human health and disease [...] Full article

(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)

36 pages, 1562 KB

Open AccessReview

Targeting Metabolic Dysregulation in Obesity and Metabolic Syndrome: The Emerging Role of N-Acetylcysteine

by Dorota Magdalena Radomska-Leśniewska, Justyna Niderla-Bielińska, Marek Kujawa and Ewa Jankowska-Steifer

Metabolites 2025, 15(10), 645; https://doi.org/10.3390/metabo15100645 - 26 Sep 2025

Abstract

Obesity and metabolic syndrome (MetS), growing global health concerns, are closely linked to the development of insulin resistance, type 2 diabetes, steatotic liver disease, and cardiovascular diseases (CVDs). An increase in visceral adipose tissue, the main symptom of MetS, contributes to systemic metabolic [...] Read more.

Obesity and metabolic syndrome (MetS), growing global health concerns, are closely linked to the development of insulin resistance, type 2 diabetes, steatotic liver disease, and cardiovascular diseases (CVDs). An increase in visceral adipose tissue, the main symptom of MetS, contributes to systemic metabolic dysfunction, resulting in disturbances in glucose and lipid metabolism, mitochondrial dysfunction, and redox imbalance, which creates a vicious cycle of inflammation and oxidative stress, accelerating comorbidities. N-acetylcysteine (NAC), a precursor to glutathione, with antioxidant and anti-inflammatory properties, is described as a potent metabolic modulator that restores metabolic homeostasis. NAC’s ability to modulate oxidative stress and inflammation may be particularly valuable in preventing or mitigating cardiovascular complications of MetS. The aim of this narrative review is to summarize current evidence from cellular, animal, and human studies on NAC’s impact on metabolic health. MetS affects nearly one-third of the global population; therefore, there is a pressing need for accessible therapeutic strategies. NAC appears to offer potential benefits as an adjunctive agent for individuals with metabolic disturbances, but further research is needed to confirm its efficacy and establish its role in clinical practice. Full article

(This article belongs to the Special Issue Metabolic Modulators in Cardiovascular Disease Management)

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12 pages, 270 KB

Open AccessArticle

Association of Systemic Inflammation with Inflammatory mRNA Expression in Visceral Adipose Tissue in Gestational Diabetes

by Renata Saucedo, María Isabel Peña-Cano, Mary Flor Díaz-Velázquez, Alejandra Contreras-Ramos, Miranda Moleres-Orduña, Debbie López-Sánchez, Jorge Valencia-Ortega and Javier Pérez-Duran

Metabolites 2025, 15(10), 644; https://doi.org/10.3390/metabo15100644 - 26 Sep 2025

Abstract

Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) [...] Read more.

Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) investigate whether whole blood counts, the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), serum adiponectin levels, and the mRNA expression of inflammatory genes (TLR2, TLR4, pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, anti-inflammatory cytokines: IL-1RA, IL-10, and adiponectin) in VAT are altered in women with GDM in comparison to pregnant women with normal glucose tolerance (NGT), and (2) determine the correlations between systemic and local VAT inflammation in all, GDM, and NGT women. Methods: Study of 50 GDM and 50 women with NGT with a cross-sectional design. Standard biochemical and hematological tests were conducted and relative mRNA expression in VAT was measured by RT-qPCR. Results: Women with GDM showed higher neutrophil, monocyte, NLR, MLR, and VAT TNF-α/IL-10 mRNA expression ratios while lymphocyte and eosinophil counts, serum adiponectin, and mRNA local VAT inflammatory markers such as TLR2, TLR4, IL-1β, IL-6, IL-1RA, and IL-10 were lower in women with GDM relative to women with NGT. Additionally, the circulating monocyte count were associated with TLR2 and TLR-4 VAT mRNA expression levels and eosinophils count were associated with IL-1β, IL-6, IL-10, and IL-1RA VAT expression levels in women with GDM. Conclusions: GDM is characterized by systemic inflammation, and some circulating immune cells, such as monocytes and eosinophils, are associated with the expression of inflammatory markers in VAT. Full article

(This article belongs to the Special Issue Exploring Pathological Mechanisms in Obesity, Diabetes, and Metabolic Syndrome)

21 pages, 769 KB

Open AccessArticle

Phenolic Compounds from Hypericum cerastoides (Spach) N. Robson: Dereplication via UHPLC-HRMS/MS, Isolation, Identification, and Preliminary Biological Evaluation Focusing on Radical-Scavenging, Anti-α-Glucosidase, and Pro-Lipase Activities

by Zlatina Kokanova-Nedialkova, Yana Ilieva, Teodor Marinov and Paraskev T. Nedialkov

Metabolites 2025, 15(10), 643; https://doi.org/10.3390/metabo15100643 - 25 Sep 2025

Abstract

Background/Objectives: Hypericum cerastoides (Spach) N. Robson is a lesser-known species with potential pharmacological importance. This study aimed to profile phenolic compounds in its aerial parts and assess biological activities of isolated constituents, focusing on radical-scavenging, anti-α-glucosidase, and pro-lipase effects. Methods: Phenolic compounds [...] Read more.

Background/Objectives: Hypericum cerastoides (Spach) N. Robson is a lesser-known species with potential pharmacological importance. This study aimed to profile phenolic compounds in its aerial parts and assess biological activities of isolated constituents, focusing on radical-scavenging, anti-α-glucosidase, and pro-lipase effects. Methods: Phenolic compounds from H. cerastoides aerial parts were dereplicated via UHPLC-HRMS/MS. The structures of isolated compounds were determined using spectroscopic methods (1D and 2D NMR, UV, and HRMS-ESI). Radical-scavenging was evaluated by DPPH and ABTS assays; anti-α-glucosidase and pro-lipase activities were measured by LC-MS. Results: UHPLC-HRMS profiling of a hydroalcoholic extract tentatively identified and quantified 39 phenolic compounds, mainly flavonoids and hydroxycinnamic acid derivatives. Furthermore, two new phenolic compounds, namely hypercerastoside A (HC4) and hypercerastoside B (HC6), together with three known compounds, coumaroylquinic acid (HC1), myricetin-3-O-glycoside (HC2), and myricetin-3-O-galactoside (HC3), as well as two artifacts, namely methyl ester of chlorogenic acid (HC5) and hypercerastoside C (HC7), were isolated from the ethylacetate extract of the aerial parts of title plant. Compounds HC2, HC3, and HC5 displayed the highest radical-scavenging activity. The anti-α-glucosidase test showed that compounds HC1 (IC₅₀ = 44 µM) and HC3 (IC₅₀ = 206 µM) possessed similar activity to acarbose (IC₅₀ = 206 µM). Myricetin glycosides HC2 and HC3 enhanced lipase activity fivefold at 200 µM. Conclusions: H. cerastoides is a promising source of bioactive phenolic compounds with significant radical-scavenging and enzyme-modulating activities. These preliminary findings support further exploration of its therapeutic potential, especially for oxidative stress-related disorders, type 2 diabetes, and cachexia. Full article

(This article belongs to the Special Issue Bioactive Plant Extracts: Phytochemical Characterization, Isolation and Biological Evaluation)

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22 pages, 3716 KB

Open AccessArticle

Precision Probiotics Regulate Blood Glucose, Cholesterol, Body Fat Percentage, and Weight Under Eight-Week High-Fat Diet

by Jinhua Chi, Jeffrey S. Patterson, Lingjun Li, Nicole Lalime, Daniella Hawley, Kyle Joohyung Kim, Li Liu, Julia Yue Cui, Dorothy D. Sears, Paniz Jasbi and Haiwei Gu

Metabolites 2025, 15(10), 642; https://doi.org/10.3390/metabo15100642 - 25 Sep 2025

Abstract

Background/Objectives: Poor glycemic control is reaching an epidemic prevalence globally. It is associated with significantly morbid health concerns including retinopathy, neuropathy, nephropathy, cancer, and cardiovascular disease. Probiotics have shown promise in reducing health complications associated with poor blood glucose control. We tested [...] Read more.

Background/Objectives: Poor glycemic control is reaching an epidemic prevalence globally. It is associated with significantly morbid health concerns including retinopathy, neuropathy, nephropathy, cancer, and cardiovascular disease. Probiotics have shown promise in reducing health complications associated with poor blood glucose control. We tested a novel approach to designing a precision probiotic cocktail for improving blood glucose homeostasis. Methods: We tested the in vitro glucose consumption rate of twelve mouse microbiome bacterial strains and selected three with the greatest glucose consumption for the probiotic cocktail. The in vivo metabolic impact of ingesting the selected probiotic cocktail was evaluated in twelve C57BL/6J male mice fed a high-fat diet for eight weeks. Results: Compared to a control group, the probiotic group (L. rhamnosus, L. reuteri, and L. salivarius) exhibited significantly lower blood glucose levels, body weight, and body fat percentage. Moreover, the probiotic cocktail also demonstrated the ability to reduce serum insulin, total cholesterol, very-low-density lipoprotein/low-density lipoprotein cholesterol, and total cholesterol to high-density lipoprotein ratio. For further mechanistic investigation, untargeted metabolomics analyses uncovered overall downregulations in energy substrates and producing pathways like gluconeogenesis, acylcarnitine synthesis, glycolysis, the mitochondrial electron transport chain, the TCA cycle, and the building blocks for ATP formation. Partial least squares-discriminant analyses also confirmed clear group differences in metabolic activity. 16S rRNA sequencing from extracted gut microbiota also showed significant increases in Faith’s phylogenetic diversity, Lachnospiraceae bacterium 609-strain, and the genus Muribaculaceae as well as group β-diversity differences after probiotic intake. Conclusions: As such, we successfully developed a blend of three probiotics to effectively reduce blood glucose levels in male mice, which could further mitigate adverse health effects in the host. Full article

(This article belongs to the Special Issue Role of Nutraceuticals in Metabolic Disorders: Mechanisms and Benefits)

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13 pages, 1004 KB

Open AccessArticle

Matched Metabolic Stress Preserves Myokine Responses Regardless of Mechanical Load: A Randomized, Controlled Crossover Trial

by Yuji Maki, Hiroo Matsuse, Ryuki Hashida, Norika Matsukuma, Hiroshi Tajima, Eriko Baba, Yuji Kaneyuki, Sohei Iwanaga, Masayuki Omoto, Yoshio Takano, Matsuo Shigeaki, Takeshi Nago and Koji Hiraoka

Metabolites 2025, 15(10), 641; https://doi.org/10.3390/metabo15100641 - 25 Sep 2025

Abstract

Background/Objectives: Skeletal muscle functions as an endocrine organ by secreting myokines in response to exercise, with interleukin-6 (IL-6) recognized as a representative intensity-dependent biomarker that rapidly increases immediately after exercise and is strongly dependent on exercise intensity. However, it is unclear how [...] Read more.

Background/Objectives: Skeletal muscle functions as an endocrine organ by secreting myokines in response to exercise, with interleukin-6 (IL-6) recognized as a representative intensity-dependent biomarker that rapidly increases immediately after exercise and is strongly dependent on exercise intensity. However, it is unclear how changes in mechanical stress affect the response of myokines after exercise. This randomized crossover study aimed to investigate the effect of mechanical stress on acute myokine secretion during matched metabolic exercise under different mechanical stress. Methods: Ten healthy adult males performed 30 min of cycling at 60% of peak

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O₂ in both semi-recumbent position and side-lying positions. Blood samples were collected before, immediately after, and at 30 and 60 min post-exercise to evaluate IL-6, brain-derived neurotrophic factor (BDNF), and lactate. Results: BDNF and lactate levels peaked immediately after exercise, and IL-6 reached its peak at 30 min post-exercise in both the semi-recumbent position and side-lying positions. All markers showed significant elevations in response to exercise. However, no significant differences were found between the two postures in any of the measured variables. Conclusions: These findings suggest that reduced mechanical load does not impair endocrine responses when the intensity of metabolic stress is maintained. This study provides scientific evidence that, regardless of posture or environment, sufficient exercise intensity can induce adequate IL-6 and BDNF secretion, through which the beneficial effects of exercise may be expected. Full article

(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment: 2nd Edition)

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12 pages, 1928 KB

Open AccessArticle

Chemometric Discrimination of Korean and Chinese Kimchi Using Untargeted Metabolomics

by Quynh-An Nguyen, Dong-Shin Kim, Hyo-Dong Kim, Kyu-Bin Kim, Kyung-Sik Ham, Yonghoon Lee and Hyun-Jin Kim

Metabolites 2025, 15(10), 640; https://doi.org/10.3390/metabo15100640 - 25 Sep 2025

Abstract

Background/Objectives: Kimchi has gained global recognition for its unique taste and health benefits, but its quality is totally different according to its geographical origin of materials and production methods. Methods: In this study, differences between Korean (53 samples) and Chinese kimchi (72 samples) [...] Read more.

Background/Objectives: Kimchi has gained global recognition for its unique taste and health benefits, but its quality is totally different according to its geographical origin of materials and production methods. Methods: In this study, differences between Korean (53 samples) and Chinese kimchi (72 samples) were investigated through comprehensive metabolomic analysis using gas chromatography–mass spectrometry (GC-MS) and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS). Results: Multivariate statistical analyses revealed a clear separation between the two groups. Thirty-four metabolites contributing to the separation were identified. Korean kimchi was enriched in sucrose, quinic acid, sinapic acid derivatives, rutin, capsicosin, and capsianoside, while Chinese kimchi contained higher levels of trihydroxy octadecenoic acid, 2-hydroxypalmitic acid, pinellic acid, maltose, glucuronic acid, and corchorifatty acid F. In particular, the univariate Bayesianlogistic regression analysis revealed that among these metabolites, rutin, capsicosin derivatives, and sinapic acid derivatives showed strong potential as origin-discriminant markers of kimchi, providing insights into how these metabolites influence its nutritional and sensory properties. Conclusions: These compositional differences may be attributed to variations in raw materials and production methods of kimchi. Full article

(This article belongs to the Section Food Metabolomics)

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11 pages, 255 KB

Open AccessReview

Vitamin D Metabolism and the Risk of Renal Stones: A Focus on PHPT

by Elena Castellano and Federica Saponaro

Metabolites 2025, 15(10), 639; https://doi.org/10.3390/metabo15100639 - 24 Sep 2025

Abstract

Primary hyperparathyroidism is nowadays a common endocrine disorder. Over time, the clinical manifestation has shifted from symptomatic cases to mostly asymptomatic diagnoses. Despite this, nephrolithiasis remains significant, often presenting as bilateral and recurrent, with the literature reporting prevalence rates of up to 40%. [...] Read more.

Primary hyperparathyroidism is nowadays a common endocrine disorder. Over time, the clinical manifestation has shifted from symptomatic cases to mostly asymptomatic diagnoses. Despite this, nephrolithiasis remains significant, often presenting as bilateral and recurrent, with the literature reporting prevalence rates of up to 40%. The nephrolithiasis pathogenesis in PHPT is multifactorial and not fully understood. While elevated PTH increases urinary calcium load, additional urinary abnormalities and demographic factors, including age and sex, influence the risk. Vitamin D status has also been explored as a possible contributor to stone formation both in the general population and in PHPT patients. The relationship between serum 25OHD levels and nephrolithiasis remains unclear, and the impact of vitamin D supplementation on stone risk in PHPT is still under investigation. The relationship between vitamin D status, supplementation and renal stones in PHPT is explored in the present review. Full article

(This article belongs to the Special Issue Primary Hyperparathyroidism: Mechanisms and Treatment)

18 pages, 1886 KB

Open AccessArticle

Effect of β-Caryophyllene on PPAR-γ, NF-κB, and CNR2: Implications for Gut–Brain Axis Communication in a Murine Model of Diet-Induced Obesity

by Cristina Pech-Jiménez, Lucrecia Carrera-Quintanar, Juan Manuel Viveros-Paredes, Yolanda Fabiola Marquez-Sandoval, Luis Felipe Jave-Suárez, Adelaida Sara Minia Zepeda-Morales, Gilberto Velázquez-Juárez and Rocio Ivette López-Roa

Metabolites 2025, 15(10), 638; https://doi.org/10.3390/metabo15100638 - 24 Sep 2025

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Abstract

Background /Objectives: The rising prevalence of metabolic disorders, such as obesity, is linked to increased consumption of high-calorie foods and sedentary lifestyles. While conventional treatments rely on lifestyle modifications and pharmaceuticals, these often have limitations and adverse effects. As an alternative, natural compounds [...] Read more.

Background /Objectives: The rising prevalence of metabolic disorders, such as obesity, is linked to increased consumption of high-calorie foods and sedentary lifestyles. While conventional treatments rely on lifestyle modifications and pharmaceuticals, these often have limitations and adverse effects. As an alternative, natural compounds like β-caryophyllene (BCP), found in spices such as black pepper and cloves, have gained interest due to their anti-inflammatory and metabolic properties. This study investigated the effects of BCP on the gut–brain axis in obese C57BL/6J mice. Methods: Quantitative real-time PCR (RT-qPCR) was performed using a Rotor-GeneQ thermocycler (Qiagen). Relative gene expression levels were normalized to the reference gene’s transcript levels (2^−∆∆Ct method). Results: BCP was found to modulate key receptors, including FFAR3, LEPR, and GHSR, which are involved in appetite regulation and insulin sensitivity. Its action on the CNR2 (CB2 receptor) suggests additional benefits in energy balance and anorexigenic activity. Conclusions: These findings support BCP’s potential as a complementary therapy for obesity, though further studies are needed to confirm its efficacy in humans. Its safety profile and multifactorial effects make it a promising alternative to conventional treatments. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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25 pages, 6097 KB

Open AccessArticle

Hexavalent Chromium Induces Defense Responses, Hepatocellular Apoptosis, and Lipid Metabolism Alterations in New Zealand Rabbit Livers

by Junzhao Yuan, Lei Zhang, Xiuqing Li, Xinfeng Li, Pandeng Zhao, Xiaoli Ren and Yuzhen Song

Metabolites 2025, 15(10), 637; https://doi.org/10.3390/metabo15100637 - 23 Sep 2025

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Abstract

Background: Hexavalent chromium (Cr(VI)) can migrate into soil and water, posing risks to animal health. However, it remains unclear whether Cr(VI) perturbs essential trace elements and antioxidant gene expression, triggers apoptosis, or disrupts hepatic lipid metabolism in New Zealand rabbits. Methods: [...] Read more.

Background: Hexavalent chromium (Cr(VI)) can migrate into soil and water, posing risks to animal health. However, it remains unclear whether Cr(VI) perturbs essential trace elements and antioxidant gene expression, triggers apoptosis, or disrupts hepatic lipid metabolism in New Zealand rabbits. Methods: To address this knowledge gap, twenty-four 30-day-old New Zealand rabbits were randomly allocated to one control and three Cr(VI)-treated groups (differing in Cr(VI) concentration) and maintained for 28 days. Livers were then harvested for analysis. Total Cr and essential trace elements were quantified by ICP-OES. Hematoxylin–eosin staining and transmission electron microscopy were employed to assess histopathological and ultrastructural alterations, respectively. Hepatic lipid accumulation was visualized with Oil Red O staining. QRT-PCR was used to determine the expression of antioxidant and lipid-metabolism-related genes. Results: Cr(VI) was detectable in liver tissue at all exposure levels and was accompanied by significant decreases in four essential trace elements (Fe, Mn, Zn, and Se); Cu displayed a biphasic response, rising at lower Cr(VI) doses before declining at higher doses. Histopathological and ultrastructural analyses revealed overt hepatic injury. Notably, all Cr(VI) treatments elevated antioxidant gene expression, indicating activation of hepatic defense pathways. Lipid metabolism was also disrupted, evidenced by increased lipid deposition and up-regulation of genes governing hepatic fat metabolism. Conclusions: Collectively, these findings demonstrate that Cr(VI) elicits dose-dependent activation of hepatic antioxidant defenses, promotes apoptosis, and induces lipid-metabolic disorders in New Zealand rabbit hepatocytes. This study provides novel mechanistic insights into Cr(VI)-induced hepatotoxicity and offers a valuable reference for evaluating the hepatic risks of environmental Cr(VI) exposure in this species. Full article

(This article belongs to the Special Issue Animal Nutritional Metabolism and Toxicosis Disease, 2nd Edition)

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17 pages, 2668 KB

Open AccessArticle

NAD⁺-Dependent Lysine Acetylation Regulates Glucose Uptake and Fatty Acid Oxidation in Cardiomyocytes

by Ettore Vanni and Christophe Montessuit

Metabolites 2025, 15(10), 636; https://doi.org/10.3390/metabo15100636 - 23 Sep 2025

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Abstract

Background/Objectives: Stimulation of glucose uptake in response to ischemic stress is important for cardiomyocyte post-ischemic function and survival. In the diabetic myocardium chronically exposed to an excess of circulating lipids, this mechanism is impaired, making the myocardium more sensitive to ischemia–reperfusion injury (IRI). [...] Read more.

Background/Objectives: Stimulation of glucose uptake in response to ischemic stress is important for cardiomyocyte post-ischemic function and survival. In the diabetic myocardium chronically exposed to an excess of circulating lipids, this mechanism is impaired, making the myocardium more sensitive to ischemia–reperfusion injury (IRI). In vitro studies have shown that exposure to fatty acids (FAs) reduces basal and stimulated glucose uptake in cardiomyocytes. Preliminary results indicate reduced NAD⁺ levels and increased protein lysine acetylation in FA-exposed cardiomyocytes. This study aims to investigate whether intracellular NAD⁺ reduction is responsible for FA-induced increase in protein acetylation and impaired glucose uptake. Methods: Primary rat cardiomyocytes were chronically treated with the sirtuin deacetylase inhibitor nicotinamide (NAM) in absence of FAs to induce protein acetylation. Conversely, we replenished NAD⁺ concentration using nicotinamide riboside (NR) to induce protein deacetylation in FA-exposed cardiomyocytes. Results: Similar to FA exposure, NAM treatment increased protein acetylation and impaired metabolic-stress-stimulated glucose uptake in cardiomyocytes. In contrast, NR supplementation reduced protein acetylation and improved metabolic-stress-stimulated glucose uptake in FA-exposed cardiomyocytes. Neither NAM nor NR influenced insulin-stimulated glucose uptake. Both NAM and FAs induced hydroxyacyl-CoA dehydrogenase trifunctional enzyme subunit α (HADHA) acetylation on lysine residues K¹⁶⁶ and K²¹⁴ and enhanced palmitate oxidation. Conversely, NR treatment induced HADHA deacetylation and reduced palmitate uptake and oxidation in FA-exposed cardiomyocytes. Conclusions: In cardiomyocytes, protein hyperacetylation, resulting from either FA exposure or sirtuin inhibition, impairs metabolic-stress-stimulated glucose uptake and is associated with increased FA oxidation. Full article

(This article belongs to the Section Cell Metabolism)

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Metabolites, Volume 15, Issue 10 (October 2025) – 11 articles

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