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Purpose: Continuous glucose monitors (CGMs) are becoming increasingly popular among endurance athletes despite unconfirmed accuracy. We assessed the concurrent validity of the FreeStyle Libre 2 worn on 2 different sites at rest, during steady-state running, and postprandial. Methods: Thirteen nondiabetic, well-trained recreational runners (age = 40 [8] y, maximal aerobic oxygen consumption = 46.1 [6.4] mL·kg–1·min–1) wore a CGM on the upper arm and chest while treadmill running for 30, 60, and 90 minutes at intensities corresponding to 50%, 60%, and 70% of maximal aerobic oxygen consumption, respectively. Glucose was measured by manually scanning CGMs and obtaining a finger-prick capillary blood glucose sample. Mean absolute relative difference, time in range, and continuous glucose Clarke error grid analysis were used to compare paired CGM and blood glucose readings. Results: Across all intensities of steady-state running, we found a mean absolute relative difference of 13.8 (10.9) for the arm and 11.4 (9.0) for the chest. The coefficient of variation exceeded 70%. Approximately 47% of arm and 50% of chest paired glucose measurements had an absolute difference ≤10%. Continuous glucose Clarke error grid analysis indicated 99.8% (arm) and 99.6% (chest) CGM data fell in clinically acceptable zones A and B. Time-in-range analysis showed reduced accuracy at lower glucose levels. However, CGMs accurately detected trends in mean glucose readings over time. Conclusions: CGMs are not valid for point glucose monitoring but appear to be valid for monitoring glucose trends during steady-state exercise. Accuracy is similar for arm and chest. Further research is needed to determine whether CGMs can detect important events such as hypoglycemia during exercise. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is an ALS-specific multi-domain screening tool. Few studies have examined the relationship between ECAS scores and [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) findings. Objective: To assess the relationship between ECAS scores and glucose metabolism patterns on [18F]FDG -PET images in ALS. Methods: We collected [18F]FDG-PET images from 65 patients with ALS and 39 healthy controls. ECAS scores were collected on all patients and we calculated the correlation to [18F]FDG-PET in order to investigate the potential links between cognition and glucose metabolism. Results: We observed hypometabolism in the frontal cortex, insula, and limbic system, together with hypermetabolism in the cerebellum in patients with ALS compared to controls. A lower ECAS total score was associated with lower glucose metabolism in the right orbitofrontal gyrus and higher glucose metabolism in lateral occipital, medial occipital, and cerebellar regions, among patients with ALS. Similar results, although less widespread, were observed in the analyses of ECAS ALS-specific scores. Conclusions: The metabolic patterns in [18F]FDG -PET show that changes in the glucose metabolism of corresponding areas are related to cognitive dysfunction in ALS, and can be detected using the ECAS. [ABSTRACT FROM AUTHOR]

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches. [ABSTRACT FROM AUTHOR]

Background: About two-thirds of those with Alzheimer's disease (AD) are women, most of whom are post-menopausal. Menopause accelerates dementia risk by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid-life metabolic disease (obesity, diabetes/prediabetes) is a well-known risk factor for dementia. A high fat diet can lead to poor metabolic health in both humans and rodents. Objective: Our goal was to determine the effects of a high fat diet on metabolic outcomes in the AppNL-F knock-in mouse model of AD and assess the effects of menopause. Methods: First, 3-month-old AppNL-F and WT female mice were placed on either a control or a high fat diet until 10 months of age then assessed for metabolic outcomes. Next, we did a more extensive assessment in AppNL-F mice that were administered VCD (4-vinylcyclohexene diepoxide) or vehicle (oil) and placed on a control or high fat diet for 7 months. VCD was used to model menopause by causing accelerated ovarian failure. Results: Compared to WT controls, AD female mice had worse glucose intolerance. Menopause led to metabolic impairment (weight gain and glucose intolerance) and further exacerbated obesity in response to a high fat diet. There were interactions between diet and menopause on some metabolic health serum biomarkers and the expression of hypothalamic markers related to energy balance. Conclusions: This work highlights the need to model endocrine aging in animal models of dementia and will contribute to further understanding the interaction between menopause and metabolic health in the context of AD. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which activated CD4+ T cells participate in the disease process by inducing inflammation. We aimed to investigate the role of Toll-like receptor 2 (TLR2) on CD4+ T cells in RA patients, and to elucidate the underlying mechanisms by which TLR2 contributes to the pathogenesis of RA. Methods: Serum samples were collected from RA patients and healthy controls. Soluble TLR2 levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to assess the TLR2 expression level, activation status, cytokine production, reactive oxygen species (ROS) levels, and glucose uptake capacity of CD4+ T cells. Quantitative polymerase chain reaction (qPCR) was used to measure the expression of enzymes associated with glucose and lipid metabolism. The concentration of lactic acid in the culture supernatant was determined using a dedicated detection kit. Results: RA patients had higher levels of TLR2 in their serum, which positively correlated with C-reactive protein and rheumatoid factor. The expression level of TLR2 in CD4+ T cells of RA patients was increased, and TLR2+ cells showed higher activation levels than TLR2- cells. Activation of TLR2 in CD4+ T cells of RA patients promoted their activation, TNF-α secretion, and increased production of ROS. Furthermore, TLR2 activation led to changes in enzymes related to glucose metabolism, causing a shift in glucose metabolism towards the pentose phosphate pathway. Blocking oxidative phosphorylation and the pentose phosphate pathway had varying effects on CD4+ T cell function. Conclusion: TLR2 reprograms the glucose metabolism of CD4+ T cells in RA patients, contributing to the development of RA through ROS-mediated cell hyperactivation and TNF-α secretion. Key Points • TLR2 is upregulated in CD4+T cells of RA patients and correlates with disease severity markers such as CRP and RF. • Activation of TLR2 in CD4+T cells promotes cell activation, TNF-α secretion, and increased ROS production, contributing to the pathogenesis of RA. • TLR2 activates glucose metabolism in CD4+T cells, shifting towards the pentose phosphate pathway, which may be a novel therapeutic target for RA treatment. • Blocking glucose metabolism and ROS production can reduce CD4 + T cell hyperactivation and TNF-α secretion, indicating potential therapeutic strategies for RA management. [ABSTRACT FROM AUTHOR]

Objective: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes. Methods: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6–18 years who underwent dual‐energy X‐ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta‐Analysis of Glucose and Insulin‐Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). Results: In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA‐IR) and homeostasis model assessment of pancreatic beta cell function (HOMA‐β) through FGF23, whereas fat‐free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat‐free mass with fasting glucose, fasting insulin and HOMA‐IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat‐free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01–1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77–0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: −0.05 [95% CI: −0.07, −0.02]) and fat‐free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose. Conclusions: Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses. [ABSTRACT FROM AUTHOR]

Abnormal glucose metabolism is a common disease of the endocrine system. The effects of drugs on glucose metabolism have been reported frequently in recent years, and since abnormal glucose metabolism increases the risk of microvascular and macrovascular complications, metabolic disorders, and infection, clinicians need to pay close attention to these effects. A variety of common drugs can affect glucose metabolism and have different mechanisms of action. Hypertension is a common chronic cardiovascular disease that requires long‐term medication. Studies have shown that various antihypertensive drugs also have an impact on glucose metabolism. Among them, α‐receptor blockers, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers can improve insulin resistance, while β‐receptor blockers, thiazides and loop diuretics can impair glucose metabolism. The aim of this review was to discuss the mechanisms underlying the effects of various antihypertensive drugs on glucose metabolism in order to provide reference information for rational clinical drug use. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that disturbance of the clock genes, which leads to systemic endocrine perturbation, plays a crucial role in the pathogenesis of metabolic and liver diseases. Fluorene-9-bisphenol (BHPF) is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown. The impacts and involved mechanisms of BHPF on the liver diseases, metabolism, and circadian clock were comprehensively studied by zebrafish and mouse models. The therapeutic effect of melatonin (MT) was also verified. Zebrafish and mouse models with either acute exposure (0.5 and 1 µmol/L, 1-4 days post-fertilization) or chronic oral exposure (0.5 and 50 mg/(kg·2 days), 30 days) were established with various BHPF concentrations. Herein, we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model. BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain. The liver sexual dimorphic alteration along with reduced growth hormone and estrogens played a critical role in damaged glucose metabolism, hepatic inflammation, and fibrosis induced by BHPF. Besides, sleep improvement by exogenous MT alleviated BHPF‐related glucose metabolism and liver injury in mice. We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for liver metabolism disorders associated with endocrine perturbation chemicals. These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Context Body composition and glucose metabolism change with aging. Whether different levels of body-mass-index (BMI) are needed to define diabetes risk across the adult lifespan is unknown. Objective This work aimed to investigate whether BMI similarly reflects relative fat mass (FM) and diabetes risk across age groups. Methods Participants without diabetes from the Baltimore Longitudinal Study of Aging (973 men, 1073 women), stratified by age (<50, 50-59, 60-69, ≥70 years) and categorized by either World Health Organization (WHO)-defined BMI categories (for normal weight, overweight or obesity) or BMI quartiles. The primary exposure was BMI. The primary outcome was diabetes incidence. The relationship of BMI to dual-energy x-ray absorptiometry–derived FM was also investigated in older vs younger participants. Results The median (range) follow-up time was 7.1 years (range, 0-29.0 years). Within WHO-defined BMI categories, different age groups demonstrated significantly different FM percentage, FM/lean mass, and waist circumference (P <.05). WHO-defined BMI categories for overweight and obesity were generally related to higher diabetes risk compared to normal weight in all ages except 50 to 59 years. When BMI was categorized by quartiles, diabetes incidence increased dramatically beginning in quartile 2 (23-25 kg/m2) in older groups. BMI cutoffs with equivalent diabetes incidence rate as BMI 25 kg/m2 and 30.0 kg/m2 in individuals younger than 50 years were 22.7 kg/m2 and 25.2 kg/m2 for ages 50 to 59 years; 22.8 kg/m2 and 25.0 kg/m2 for ages 60 to 69 years; and 23.2 kg/m2 and 25.8 kg/m2 for ages 70 years and older, respectively. Conclusion WHO-defined BMI categories do not reflect similar diabetes risk across the lifespan. Diabetes incidence is greater at lower levels of BMI in older adults and may lead to underestimation of diabetes risk with aging, particularly among those traditionally classified as normal-weight individuals. [ABSTRACT FROM AUTHOR]

Background: ADHD is highly comorbid with Delayed Sleep Phase Syndrome (DSPS). Both are associated with obesity and diabetes, which can be caused by long-term dysregulations of appetite and glucose metabolism. This study explores hormones involved in these processes and the effects of chronotherapeutic interventions in a small sample of adults with ADHD and DSPS. Methods: Exploratory, secondary analysis of data from the PhASE study, a three-armed randomized clinical trial, are presented, including 37 adults (18–53 years) with ADHD and DSPS receiving three weeks of 0.5 mg/day (1) placebo, (2) melatonin, or (3) melatonin plus 30 minutes of bright light therapy (BLT). Leptin (appetite-suppressing), ghrelin (appetite-stimulating), insulin, insulin-like growth factor-1 (IGF-1), and glucose were measured from blood collected at 08:00 hours. Salivary cortisol was collected during the first 30 minutes after awakening and self-reported appetite was assessed. Results: Baseline leptin and IGF-1 levels were higher than reference ranges, and ghrelin and cortisol levels were lower, while insulin and glucose were normal. Melatonin treatment decreased leptin and insulin. Other outcomes remained unchanged and melatonin + BLT had no effects. Conclusion: Due to the small sample size and exploratory nature of the study, results should be interpreted with caution. Overall, these results show no strong indications for dysregulation of appetite and glucose metabolism to suggest high risk of obesity and diabetes in this small sample of adults with ADHD and DSPS. However, baseline appetite was suppressed, likely because measurements took place in the early morning which could be considered the biological night for this study population. Melatonin treatment seemed to cause subtle changes in appetite-regulating hormones suggesting increased appetite. Chronotherapeutic treatment may affect appetite-regulating hormones by advancing the biological rhythm and/or altering eating behaviors, but this remains to be investigated in larger samples using detailed food diaries. [ABSTRACT FROM AUTHOR]

Purpose We aimed to investigate the association between maternal fasting plasma glucose (FPG) trajectories during pregnancy and children's refractive errors at 6 years of age. Design Based on the Ma'anshan Birth Cohort (MABC) in China, a total of 1987 mother-child pairs were included in this study. Methods Using the group-based trajectory model, trajectory fitting was performed on FPG levels during the first, second, and third trimesters of pregnancy. Children's vision was measured at 6 years of age using the standard logarithmic visual acuity E-chart and cycloplegic refraction examination. Logistic regression models and multi-informant generalized estimating equations were used to analyze the association between maternal blood glucose level and 6-year-old children's visual acuity. Results Children born of mothers with high level FPG trajectory had a higher risk of developing refractive error (odds ratio [OR] = 1.46 [95% CI: 1.08, 1.97]), hypermetropia (OR = 1.64 [95% CI: 1.09, 2.46]), and astigmatism (OR = 1.60 [95% CI: 1.06, 2.41]) at age 6 compared to those with low level trajectory. Maternal blood glucose level in the first (β = −.012 [95% CI: −.024, −.001]) and the second (β = −.016 [95% CI: −.025, −.006]) trimesters was associated with 6-year-old children's distance vision value. Conclusion High level of FPG trajectories during pregnancy has been observed to be associated with 6-year-old children's refractive error, hypermetropia, and astigmatism. The first and the second trimesters may be critical periods for the effects of maternal blood glucose on children's vision. The long-term effect of maternal glucose metabolism on children's visual development deserves further study. [ABSTRACT FROM AUTHOR]

Mastitis is a significant and costly disease in dairy cows, reducing milk production and affecting herd health. Recent research highlights the role of gastrointestinal microbial dysbiosis in the development of mastitis. This review focuses on how microbial imbalances in the rumen and intestines can compromise the integrity of the gastrointestinal barriers, allowing harmful bacteria and endotoxins, such as lipopolysaccharide, to enter the bloodstream and reach the mammary gland, triggering inflammation. This process links gastrointestinal health to mammary gland inflammation through the gut–mammary axis. Furthermore, disruptions in glucose metabolism and immune responses are implicated in the progression of mastitis. This review underscores the potential for non‐antibiotic interventions aimed at restoring microbial balance to reduce mastitis incidence, providing new insights into improving dairy cow health and farm productivity. Our findings emphasise the critical need to explore preventive measures targeting the rumen and intestinal microbiota for effective mastitis control. [ABSTRACT FROM AUTHOR]

Background: Succinic acid (SA) is an important bio-based C4 platform chemical with versatile applications, including the production of 1,4-butanediol, tetrahydrofuran, and γ-butyrolactone. The non-conventional yeast Yarrowia lipolytica has garnered substantial interest as a robust cell factory for SA production at low pH. However, the high concentrations of SA, especially under acidic conditions, can impose significant stress on microbial cells, leading to reduced glucose metabolism viability and compromised production performance. Therefore, it is important to develop Y. lipolytica strains with enhanced SA tolerance for industrial-scale SA production. Results: An SA-tolerant Y. lipolytica strain E501 with improved SA production was obtained through adaptive laboratory evolution (ALE). In a 5-L bioreactor, the evolved strain E501 produced 89.62 g/L SA, representing a 7.2% increase over the starting strain Hi-SA2. Genome resequencing and transcriptome analysis identified a mutation in the 26S proteasome regulatory subunit Rpn1, as well as genes involved in transmembrane transport, which may be associated with enhanced SA tolerance. By further fine-tuning the glycolytic pathway flux, the highest SA titer of 112.54 g/L to date at low pH was achieved, with a yield of 0.67 g/g glucose and a productivity of 2.08 g/L/h. Conclusion: This study provided a robust engineered Y. lipolytica strain capable of efficiently producing SA at low pH, thereby reducing the cost of industrial SA fermentation. [ABSTRACT FROM AUTHOR]

This study investigates the hepatoprotective effects of olive oil and flaxseed oil on chemically induced hepatotoxicity in rats by evaluating key biochemical parameters, including free fatty acids, iodine value, liver enzymes (ALP, ALT, AST), cholesterol, triglycerides, and HDL levels. The results demonstrated significant improvements in these markers with the administration of olive oil and flaxseed oil, either individually or in combination. The free fatty acid percentages and iodine values were consistent with the known nutritional properties of the oils. Notably, the combination of olive oil and flaxseed oil yielded the most substantial benefits, reducing ALP (115.53 ± 0.44 U/L), ALT (50.77 ± 1.46 U/L), and AST (52.12 ± 0.36 U/L) levels while improving lipid profiles by lowering cholesterol (135.4 ± 1.43 mg/dL) and triglyceride levels (57.14 ± 2.35 mg/dL) and increasing HDL levels (49.20 ± 0.45 mg/dL). These findings suggest that olive oil and flaxseed oil, due to their antioxidant and anti‐inflammatory properties, can effectively mitigate liver damage and promote lipid metabolism. The study supports the potential therapeutic application of these oils in managing liver health and preventing hepatotoxicity. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionPancreatic β-cells play a critical role in regulating plasma insulin levels and glucose metabolism balance, with their dysfunction being a key factor in the progression of diabetes. This review aims to explore the role of autophagy, a vital cellular self-maintenance process, in preserving pancreatic β-cell functionality and its implications in diabetes pathogenesis.We examine the current literature on the role of autophagy in β-cells, highlighting its function in maintaining cell structure, quantity, and function. The review also discusses the effects of both excessive and insufficient autophagy on β-cell dysfunction and glucose metabolism imbalance. Furthermore, we discuss potential therapeutic agents that modulate the autophagy pathway to influence β-cell function, providing insights into therapeutic strategies for diabetes management.Autophagy acts as a self-protective mechanism within pancreatic β-cells, clearing damaged organelles and proteins to maintain cellular stability. Abnormal autophagy activity, either overactive or deficient, can disrupt β-cell function and glucose regulation, contributing to diabetes progression.Autophagy plays a pivotal role in maintaining pancreatic β-cell function, and its dysregulation is implicated in the development of diabetes. Targeting the autophagy pathway offers potential therapeutic strategies for diabetes management, with agents that modulate autophagy showing promise in preserving β-cell function. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non‐invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague–Dawley rats were imaged with [11C]UCB‐J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB‐J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB‐J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof‐of‐concept study shows for the first time that acute taVNS for 30 min can modulate in vivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS. [ABSTRACT FROM AUTHOR]

Gliomas are malignant tumors originating from both neuroglial cells and neural stem cells. The involvement of neural stem cells contributes to the tumor's heterogeneity, affecting its metabolic features, development, and response to therapy. This review provides a brief introduction to the importance of metabolism in gliomas before systematically categorizing them into specific groups based on their histological and molecular genetic markers. Metabolism plays a critical role in glioma biology, as tumor cells rely heavily on altered metabolic pathways to support their rapid growth, survival, and progression. Dysregulated metabolic processes, involving carbohydrates, lipids, and amino acids not only fuel tumor development but also contribute to therapy resistance and metastatic potential. By understanding these metabolic changes, key intervention points, such as mutations in genes like RTK, EGFR, RAS, and IDH can be identified, paving the way for novel therapeutic strategies. This review emphasizes the connection between metabolic pathways and clinical challenges, offering actionable insights for future research and therapeutic development in gliomas. [ABSTRACT FROM AUTHOR]

Maize is one of the most successful crops in utilizing heterosis which significantly improves maize stresses resistance and yield. Drought is a destructive abiotic stress that significantly reduces crop yield, particularly in maize. Drought stress and rewatering frequently occur during the growth and development of maize; however, themolecular mechanisms of heterosis under drought stress and re-watering have rarely been systematically investigated. Zhengdan7137 and Zhengdan7153 are two maize hybrid varieties with robust heterosis, and separately belongs to the SS×NSS and Reid×Tangsipingtou heterotic groups. 54 transcriptomes of these two hybrids and their parental inbred lines were analyzed under well-watering (WW), waterdeficit (WD), and re-watering (RW) conditions using RNA-Seq. In this study, we identified 3,411 conserved drought response genes (CDRGs) and 3,133 conserved re-watering response genes (CRRGs) between Zhengdan7137 and Zhengdan7153. When comparing CDRGs and CRRGs to overdominance and underdominance genes, we identified 303 and 252 conservative drought response overdominance genes (DODGs) and underdominance genes (DUDGs), respectively, and 165 and 267 conservative re-watering response overdominance genes (RODGs) and underdominance genes (RUDGs), respectively. DODGs are involved in stress response-related processes, such as L-phenylalanine metabolism, carbohydrate metabolism, and heat response, whereas DUDGs are associated with glucose metabolism, pentose-phosphate shunt, and starch metabolism. RODGs and RUDGs contribute to the recovery of hybrids from drought stress by upregulating cell propagation and photosynthesis processes, and repressing stress response processes, respectively. It indicated overdominant and underdominant genes conservatively contributed to hybrid heterosis under drought stress. These results deepen our understanding of the molecular mechanisms of drought resistance, uncover conservative molecular mechanisms of heterosis under drought stress and re-watering, and provide potential targets for improving drought resistance in maize. [ABSTRACT FROM AUTHOR]

The mandarin fish (Siniperca chuatsi) is a typical carnivorous fish, which has been able to consume artificial diets after domestication in recent years. However, the potential health consequences of artificial diets in mandarin fish remain unclear. This study aimed to elucidate the molecular mechanisms underlying these concerns. Fish (initial weight: 25.1 ± 0.1 g) were fed with natural (CON group) or artificial diets (AF group) for 8 weeks. Each diet was randomly distributed to sextuplicate circular tanks (300 L) with 40 fish in each tank. The transcriptome analysis revealed significant changes in metabolism-related pathways, particularly those involved in lipid and carbohydrate metabolism. Further investigation confirmed that the artificial diets significantly increased hepatic triglyceride content and fatty acid synthase activity. The artificial diets also significantly increased hepatic glycogen and glucose-6-phosphatase activity. Furthermore, the artificial diets significantly increased hepatic malondialdehyde levels, indicating increased oxidative stress. Antioxidant defense enzyme activities and the expression of antioxidant stress-related genes were significantly decreased. Additionally, the artificial diets significantly increased the expression of proinflammatory genes, including interleukin 1 beta and interferon-gamma. These findings collectively demonstrated that the artificial diets disrupted hepatic lipid and glucose metabolism, leading to oxidative stress and inflammation, thus affecting the health status of mandarin fish. [ABSTRACT FROM AUTHOR]

Dynamic positron emission tomography and kinetic modeling play a critical role in tracer development research using small animals. Kinetic modeling from dynamic PET imaging requires accurate knowledge of an input function, ideally determined through arterial blood sampling. Arterial cannulation in mice, however, requires complex, time-consuming and terminal surgery, meaning that longitudinal studies are impossible. The aim of the current work was to develop and evaluate a non-invasive, deep-learning-based prediction model (DLIF) that directly takes the PET data as input to predict a usable input function. We first trained and evaluated the DLIF model on 68 [18F] Fluorodeoxyglucose mouse scans with image-derived targets using cross validation. Subsequently, we evaluated the performance of a trained DLIF model on an external dataset consisting of 8 mouse scans where the input function was measured by continuous arterial blood sampling. The results showed that the predicted DLIF and image-derived targets were similar, and the net influx rate constants following from Patlak modeling using DLIF as input function were strongly correlated to the corresponding values obtained using the image-derived input function. There were somewhat larger discrepancies when evaluating the model on the external dataset, which could be attributed to systematic differences in the experimental setup between the two datasets. In conclusion, our non-invasive DLIF prediction method may be a viable alternative to arterial blood sampling in small animal [18F]FDG imaging. With further validation, DLIF could overcome the need for arterial cannulation and allow fully quantitative and longitudinal experiments in PET imaging studies of mice. [ABSTRACT FROM AUTHOR]

Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1ΔGFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Mechanistically, we observed that GLUT1-deficient astrocytes exhibited increased insulin receptor-dependent ATP release, and that both astrocyte insulin signaling and brain purinergic signaling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its depletion triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis, and cognitive function. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionsCapsiate (cap) is a metabolite that affects a number of biological processes, and diabetic retinopathy (DR) is now known to be the primary cause of end-stage eye illness.In order to examine the effects of the cap intervention on body weight, nutritional intake, changes in body weight composition, glucose metabolism levels, retinopathy, and oxidative stress levels, we proposed using a mouse model of diabetic retinopathy caused by STZ.Our findings demonstrated that, in addition to increasing lean body mass and lowering fat body mass content, cap intervention significantly improved body weight and dietary consumption in STZ mice. Additionally, our results on glucose metabolism revealed that cap had a significant impact on insulin resistance and the stabilization of OGTT levels. In conclusion, we examined the levels of oxidative stress and retinopathy. We discovered that the cap intervention greatly reduced the levels of MDA and significantly improved the levels of VEGF and retinopathy. In contrast, the STZ group’s levels of SOD, CAT, and GSH were significantly higher.According to our research, the Cap intervention improved the damage caused by diabetic retinopathy by reversing the levels of oxidative stress and the disrupted state of glucose metabolism, which in turn decreased the levels of VEGF. [ABSTRACT FROM AUTHOR]

Monocytes directly contribute to atherosclerosis development by their recruitment to plaques in which they differentiate into macrophages. In the present study, we ask how modulating monocyte glucose metabolism could affect their homeostasis and their impact on atherosclerosis. Here we investigate how circulating metabolites control monocyte behavior in blood, bone marrow and peripheral tissues of mice. We find that serum glucose concentrations correlate with monocyte numbers. In diet-restricted mice, monocytes fail to metabolically reprogram from glycolysis to fatty acid oxidation, leading to reduced monocyte numbers in the blood. Mechanistically, Glut1-dependent glucose metabolism helps maintain CD115 membrane expression on monocytes and their progenitors, and regulates monocyte migratory capacity by modulating CCR2 expression. Results from genetic models and pharmacological inhibitors further depict the relative contribution of different metabolic pathways to the regulation of CD115 and CCR2 expression. Meanwhile, Glut1 inhibition does not impact atherosclerotic plaque development in mouse models despite dramatically reducing blood monocyte numbers, potentially due to the remaining monocytes having increased migratory capacity. Together, these data emphasize the role of glucose uptake and intracellular glucose metabolism in controlling monocyte homeostasis and functions. Monocytes participate in plaque formation, and adapt to metabolic changes to alter their functions. Here the authors show, using genetic mouse models and functional analyses, that Glut1-mediated glucose metabolism is important for regulating monocyte homeostasis and migration, but curiously has no impact on atherosclerotic plaque formation. [ABSTRACT FROM AUTHOR]

Simple Summary: Long photoperiods are commonly used in modern intensive broiler chicken farming, which are crucial environmental factors in the growth and health of broilers. Through different photoperiods experiments, we found that extending the photoperiods could promote the growth rate of broilers while reducing the feed efficiency, inhibiting acetylcholine and its relative-acetylcholine receptor expression, and inducing glucose metabolism disorders in broilers. In addition, these findings have important implications for future research on the role of glucose metabolism, acetylcholine, and its relative acetylcholine receptors in regulating the health of broilers underlying extending the photoperiods. Photoperiods are crucial environmental factors in the growth and health of modern intensive broiler chicken production. To date, the effects of different photoperiods on glucose metabolism, acetylcholine (ACh), and its relative acetylcholine receptor modulation in broilers remain elusive. Herein, we aimed to identify the effects of different photoperiods on regulating glucose metabolism, ACh, nicotinic acetylcholine receptor alpha 4 (α4 nAChR) mRNA, and M3 muscarinic acetylcholine receptor (M3 mAChR) modulation in broilers. A total of 216 healthy 5-day-old Arbor Acres (AA) male broilers was randomly assigned to 12L:12D, 18L:6D, and 24L:0D photoperiods for 4 weeks. The results show that, compared with the 12L:12D photoperiod, the 18L:6D and 24L:0D photoperiods significantly increase the average daily gain (ADG) and average daily feed intake (ADFI) of broilers (p < 0.05). However, the feed efficiency (FE) of broilers significantly decreased in the 18L:6D and 24L:0D photoperiods (p < 0.05). Moreover, compared with the 12L:12D photoperiod, the ACh concentrations and α4 nAChR mRNA expression levels in the hypothalamus and medulla oblongata of broilers significantly increased (p < 0.05); M3 mAChR mRNA expression levels in cecum significantly reduced in the 18L:6D photoperiod and the 24L:0D photoperiod (p < 0.05). Compared with the 12L:12D photoperiod, the serum glucose (GLU), serum insulin (INS), serum triglyceride (TG) levels, and homeostasis model assessment of insulin resistance (HOMA-IR) of broilers significantly enhanced in the 18L:6D and 24L:0D photoperiods (p < 0.05). Our results indicate that extending the photoperiod can promote the growth rate, ACh expression, and α4 nAChR mRNA expression of broilers while reducing the feed efficiency, inhibiting M3 mAChR mRNA expression, and inducing glucose metabolism disorders in broilers. [ABSTRACT FROM AUTHOR]

The catalytic therapy for abundant •OH, 1O2, and •O2− provides an efficient tactic and methodology for rapid tumor/bacteria killing, whereas the limitation is focused on the catalytic efficiency owing to the in‐built energy band of catalytic materials. Thus, d‐band center tuning BioHJzyme is devised, which is composed of zinc tellurate/manganese dioxide anchored by glucose oxidase (GOx) with anti‐tumor and anti‐bacteria properties for postoperative infected wound regeneration of tumor. The GOx depletes glucose to produce H2O2, intercepting the glucose metabolism. The D‐BioHJzyme can catalyze the produced H2O2 to highly lethal •OH with POD‐mimetic activity owing to the tunned d‐band center strategy decreasing the adsorption energy of the intermediate in the catalytical process, while the oxygen originated from H2O2 and Mn2+ can be catalyzed into 1O2. The GPx‐mimetic activity of it can impair the antioxidant system of tumor. In vivo studies show that the BioHJzyme exhibits robust abilities against bacteria and tumors by •OH/1O2 production and promotes the apoptosis owing the Te. Besides, the BioHJzyme can accelerate cutaneous regeneration by M1/M2 regulation and the angiogenesis/collagen deposition. This work enlightens a powerful platform for the remedy of postoperative infected wound regeneration of tumor resection using an engineered BioHJzyme. [ABSTRACT FROM AUTHOR]

Aims: Various dietary risk factors for type 2 diabetes have been identified. A short assessment of dietary patterns related to the risk for type 2 diabetes mellitus may be relevant in clinical practice given the largely preventable nature of the disease. The aim of this study was to investigate the reproducibility of a short food frequency questionnaire based on available knowledge of diabetes-related healthy diets. In addition, we aimed to investigate whether a Diabetes Dietary Quality Index based on this questionnaire was related to metabolic risk factors, including measures of beta cell function and insulin sensitivity. Methods: A short food frequency questionnaire was composed by selecting fourteen questions (representing eight dietary factors) from existing food frequency questionnaires on the basis of their reported relationship with diabetes risk. Healthy participants (N = 176) from a Dutch family study completed the questionnaire and a subgroup (N = 123) completed the questionnaire twice. Reproducible items from the short questionnaire were combined into an index. The association between the Diabetes Dietary Quality index and metabolic risk factors was investigated using multiple linear regression analysis. Measures of beta cell function and insulin sensitivity were derived from a mixed meal test and an euglycemic–hyperinsulinemic and modified hyperglycemic clamp test. Results: Our results show that this new short food frequency questionnaire is reliable (Intraclass Correlations ranged between 0.5 and 0.9). A higher Diabetes Dietary Quality index score was associated with lower 2 h post-meal glucose (β −0.02, SE 0.006, p < 0.05), HbA1c (β −0.07, SE 0.02, p < 0.05), total cholesterol, (β −0.02, SE 0.07, p < 0.05), LDL cholesterol, (β −0.19, SE 0.07, p < 0.05), fasting (β −0.4, SE 0.16, p < 0.05) and post-load insulin, (β −3.9, SE 1.40, p < 0.05) concentrations and the incremental AUC of glucose during MMT (β −1.9, SE 0.97, p < 0.05). The scores obtained for the oral glucose insulin sensitivity-derived mixed meal test were higher in subjects who scored higher on the Diabetes Dietary Quality index (β 0.89, 0.39, p < 0.05). In contrast, we found no significant associations between the Diabetes Dietary Quality index and clamp measures of beta cell function. Conclusions: We identified a questionnaire-derived Diabetes Dietary Quality index that was reproducible and inversely associated with a number of type 2 diabetes mellitus and metabolic risk factors, like 2 h post-meal glucose, Hba1c and LDL, and total cholesterol. Once relative validity has been established, the Diabetes Dietary Quality index could be used by health care professionals to identify individuals with diets adversely related to development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

AbstractContext:Objective:Results:Conclusions: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physical activity.This study investigated glucose metabolism using the following groups of eight-week-old male Swiss mice: CS, sedentary and fed freely; RS, sedentary and RT, trained, both under 30% CR (n = 20–23 per group).Organs and fat depots of groups RS and RT were similar to CS, although body weight was lower. CR did not impair training performance nor affected systemic or hepatic glucose metabolism. Training combined with CR (group RT) improved in vivo glucose tolerance and did not affect liver gluconeogenesis.The mice tolerated the prolonged moderate CR without impairment of their well-being, glucose homeostasis, and resistance training performance. But the higher liver gluconeogenic efficiency previously demonstrated using this training protocol in mice was not evidenced under CR. [ABSTRACT FROM AUTHOR]

Wnt signaling is an important target for anabolic therapies in osteoporosis. A sclerostin-neutralizing antibody (Scl-Ab), that blocks the Wnt signaling inhibitor (sclerostin), has been shown to promote bone mass in animal models and clinical studies. However, the cellular mechanisms by which Wnt signaling promotes osteogenesis remain to be further investigated. O-GlcNAcylation, a dynamic post-translational modification of proteins, controls multiple critical biological processes including transcription, translation, and cell fate determination. Here, we report that Wnt3a either induces O-GlcNAcylation rapidly via the Ca2+-PKA-Gfat1 axis, or increases it in a Wnt-β-catenin-dependent manner following prolonged stimulation. Importantly, we find O-GlcNAcylation indispensable for osteoblastogenesis both in vivo and in vitro. Genetic ablation of O-GlcNAcylation in the osteoblast-lineage diminishes bone formation and delays bone fracture healing in response to Wnt stimulation in vivo. Mechanistically, Wnt3a induces O-GlcNAcylation at Serine 174 of PDK1 to stabilize the protein, resulting in increased glycolysis and osteogenesis. These findings highlight O-GlcNAcylation as an important mechanism regulating Wnt-induced glucose metabolism and bone anabolism. Synopsis: Wnt signaling stimulates O-GlcNAcylation either through the CaMKKII-PKA-GFAT1 axis or in a β-catenin-dependent manner, which stabilizes PDK1 protein levels and increases aerobic glycolysis, thereby facilitating osteogenesis, bone formation, and fracture healing. O-GlcNAcylation induced by Wnt3a or Scl-Ab promotes osteogenesis, bone formation, and fracture healing. Wnt/β-catenin or Wnt-CaMKKII-PKA-GFAT1 axes increase O-GlcNAcylation. Wnt-mediated O-GlcNAcylation enhances aerobic glycolysis. O-GlcNAcylation on Ser174 of PDK1 mediates Wnt3a-induced osteogenic differentiation. Wnt signaling stimulates O-GlcNAcylation either through the CaMKKII-PKA-GFAT1 axis or in a β-catenin-dependent manner, which stabilizes PDK1 protein levels and increases aerobic glycolysis, thereby facilitating osteogenesis, bone formation and fracture healing. [ABSTRACT FROM AUTHOR]

Background: Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [18F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [18F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [18F]FDG-PET/CT. Results: 155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15–20 min before [18F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [18F]FDG uptake pattern was evaluated visually and [18F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1–5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875). Conclusions: While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB. [ABSTRACT FROM AUTHOR]

The heterogeneous nuclear ribonucleoprotein C (HNRNPC) plays a crucial role in tumorigenesis, yet its role in papillary thyroid carcinoma (PTC) remains elusive. Herein, we elucidated the function and molecular mechanism of HNRNPC in PTC tumorigenesis and progression. Our study unveiled a significant upregulation of HNRNPC in PTC, and knockdown of HNRNPC markedly inhibited the proliferation, invasion, and metastasis of BCPAP cells. Furthermore, HNRNPC modulated PKM alternative splicing in BCPAP cells primarily through m6A modification. Additionally, by upregulating PKM2 expression, HNRNPC promoted aerobic glycolysis in BCPAP cells, thereby facilitating malignant progression in PTC. In summary, our findings demonstrate that HNRNPC regulates PKM alternative splicing through m6A methylation modification and promotes the proliferation, invasion and metastasis of PTC through glucose metabolism pathways mediated by PKM2. These discoveries provide new biomarkers for screening and diagnosing PTC patients and offer novel therapeutic targets for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Postpartum depression (PPD) constitutes a significant mental health disorder affecting almost one fifth of pregnancies globally. Despite extensive research, the precise etiological mechanisms underlying PPD remain elusive. However, several risk factors like genetic predisposition, hormonal fluctuations, and stress-related environmental and psychosocial triggers have been found to be implicated in its development. Main: Recently, an increased risk of PPD has been reported to be associated with gestational diabetes mellitus (GDM), which is characterized by the disruption of glucose metabolism, primarily attributed to the emergence of insulin resistance (IR). While IR during pregnancy seems to be an evolutionary adaptative mechanism to handle the profound metabolic alterations during pregnancy, its subsequent resolution following delivery necessitates a reconfiguration of the metabolic landscape in both peripheral tissues and the central nervous system (CNS). Considering the pivotal roles of energy metabolism, particularly glucose metabolism, in CNS functions, we propose a novel model that such pronounced changes in IR and the associated glucose metabolism seen postpartum might account for PPD development. This concept is based on the profound influences from insulin and glucose metabolism on brain functions, potentially via modulating neurotransmitter actions of dopamine and serotonin. Their sudden postpartum disruption is likely to be linked to mood changes, as observed in PPD. Conclusions: The detailed pathogenesis of PPD might be multifactorial and still remains to be fully elucidated. Nevertheless, our hypothesis might account in part for an additional etiological factor to PPD development. If our concept is validated, it can provide guidance for future PPD prevention, diagnosis, and intervention. [ABSTRACT FROM AUTHOR]

Key points Prolonged passive heat treatment (PHT) has been suggested to trigger skeletal muscle adaptations that may improve muscle maintenance in older individuals. To assess the effects of PHT on skeletal muscle tissue capillarization, perfusion capacity, protein synthesis rates, hypertrophy and leg strength, 14 older adults (9 males, 5 females; 73 ± 6 years) underwent 8 weeks of PHT (infrared sauna: 3× per week, 45 min at ∼60°C). Before and after PHT we collected muscle biopsies to assess skeletal muscle capillarization and fibre cross‐sectional area (CSA). Basal and postprandial muscle tissue perfusion kinetics and protein synthesis rates were assessed using contrast‐enhanced ultrasound and primed continuous l‐[ring‐13C6]phenylalanine infusions, respectively. One‐repetition maximum (1RM) leg strength and vastus lateralis muscle CSA were assessed. Type I and type II muscle fibre capillarization strongly increased following PHT (capillary‐to‐fibre perimeter exchange index: +31 ± 18 and +33 ± 30%, respectively; P < 0.001). No changes were observed in basal (0.24 ± 0.27 vs. 0.18 ± 0.11 AU; P = 0.266) or postprandial (0.20 ± 0.12 vs. 0.18 ± 0.14 AU; P = 0.717) microvascular blood flow following PHT. Basal (0.048 ± 0.014 vs. 0.051 ± 0.019%/h; P = 0.630) and postprandial (0.041 ± 0.012 vs. 0.051 ± 0.024%/h; P = 0.199) muscle protein synthesis rates did not change in response to prolonged PHT. Furthermore, no changes in vastus lateralis muscle CSA (15.3 ± 4.6 vs. 15.2 ± 4.6 cm2; P = 0.768) or 1RM leg strength (46 ± 12 vs. 47 ± 12 kg; P = 0.087) were observed over time. In conclusion, prolonged PHT increases muscle tissue capillarization but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates in healthy, older adults. Prolonged PHT does not induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults. Repeated exposure to heat has been suggested to trigger skeletal muscle adaptive responses. We investigated the effect of 8 weeks of whole‐body passive heat treatment (PHT; infrared sauna: 3× per week for 45 min at ∼60°C) on skeletal muscle tissue capillarization, perfusion capacity, basal, and postprandial muscle protein synthesis rates, muscle (fibre) hypertrophy, and leg strength in healthy, older adults. Prolonged PHT increases muscle tissue capillarization, but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates. Despite increases in muscle tissue capillarization, prolonged PHT does not suffice to induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA.The cross‐sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30–51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin‐like growth factor‐1 (IGF‐1). Blood glucose, insulin, and beta‐hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated.In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF‐1 negatively correlated with FM.Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objectives Methods Results Conclusions Pediatric‐onset Huntington's disease (POHD) exhibits a phenotype different from adult‐onset HD (AOHD), with hypokinetic movement disorders (eg, rigidity, bradykinesia, and dystonia) rather than chorea typical of AOHD.The aim was to identify pathophysiology‐based biomarkers specific to POHD (≥60 CAG repeats).Simultaneous hybrid imaging using [18F]fluoro‐2‐deoxy‐d‐glucose (FDG) positron emission tomography plus magnetic resonance imaging (FDG‐PET/MRI) and clinical assessment using standardized Huntington's disease (HD) scales were employed. Exploratory longitudinal analyses were also performed.Striatal volume loss was remarkable and more severe in POHD (n = 5) than in AOHD (n = 14). Widespread, significantly altered glucose metabolism occurred in several different POHD cortical areas and thalamus, but not AOHD cortex, consistent with differences in clinical progression.POHD patients' brains exhibited distinct morphologic and metabolic traits compared to AOHD patients’ brains, with longitudinal changes mirroring clinical progression. Hybrid FDG‐PET/MRI highlighted a variable regional brain dysfunction in vivo, as a biological consequence of highly expanded CAG repeats. Findings provide further evidence that POHD is a distinct disease from AOHD. [ABSTRACT FROM AUTHOR]

Reprogrammed glucose metabolism is considered as the hallmark of cancer with therapeutic implications. Phytocompounds have potential to inhibit cancer metabolism. Here, we tested the ability of Withaferin A (WA), a withanolide derived from Withania somnifera, in modulating cancer metabolism. The assessed effect of WA on aerobic glycolysis in breast cancer cell lines showed that WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2. We also identified that WA induced inhibition of cancer glycolysis by targeting c-myc as validated by silencing experiments followed by metabolic readouts. Decreased glycolysis resulted in reduced cell viability, biomass and colony forming ability of breast cancer cells. To further validate our in vitro findings in breast cancer patients, we analyzed 90 metabolic pathways in ~ 2000 breast tumors and observed that glycolysis is the most deregulated pathway in breast tumors. Deregulated glycolysis also predicted poor prognosis in breast cancer patients. In addition, patient data showed correlation between c-myc expression and glycolytic deregulation in breast cancer. Taken together, our results highlight the role of WA in inhibiting breast cancer metabolism via c-myc/glycolysis axis. [ABSTRACT FROM AUTHOR]

Glypican-3 (GPC-3) is predominantly found in the placenta and fetal liver, with limited expression in adult tissues. Its re-expression in hepatocellular carcinoma (HCC) and secretion into the serum highlights its potential as a diagnostic marker. GPC-3 is involved in important cellular processes such as proliferation, metastasis, apoptosis, and epithelial–mesenchymal transition through various signaling pathways including Wnt, IGF, YAP, and Hedgehog. To review the structure, biosynthesis, and post-translational modifications of GPC-3, and to elucidate its signaling mechanisms and role as a pro-proliferative protein in HCC, emphasizing its diagnostic and therapeutic potential. A comprehensive literature review was conducted, focusing on the expression of GPC-3 in various tumors, with a special emphasis on HCC. The review synthesized findings from experimental studies and clinical trials, analyzing the overexpression of GPC-3 in HCC, its differentiation from other liver diseases, and its potential as a diagnostic and therapeutic target. GPC-3 overexpression in HCC is linked to aggressive tumor behavior and poor prognosis, including shorter overall and disease-free survival. Additionally, GPC-3 has emerged as a promising therapeutic target. Ongoing investigations, including immunotherapies such as monoclonal antibodies and CAR-T cell therapies, demonstrate potential in inhibiting tumor growth and improving clinical outcomes. The review details the multifaceted roles of GPC-3 in tumorigenesis, including its impact on tumor-associated macrophages, glucose metabolism, and epithelial–mesenchymal transition, all contributing to HCC progression. GPC-3's re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3's diagnostic and therapeutic potential in HCC management. [ABSTRACT FROM AUTHOR]

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding the IR in crustaceans, particularly their role in shrimp growth and glucose metabolism. In this study, we identified a novel insulin-like receptor gene in Litopenaeus vannamei and cloned its full length of 6439 bp. This gene exhibited a highly conserved sequence and structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern analysis showed that LvRTK2 is primarily expressed in female reproductive and digestive organs. Through a series of in vivo and in vitro experiments, including glucose treatment, exogenous insulin treatment, and starvation treatment, LvRTK2 was confirmed to be involved in the endogenous glucose metabolic pathway of shrimp under different glucose variations. Moreover, long-term and short-term interference experiments with LvRTK2 revealed that the interference significantly reduced the shrimp growth rate and serum glucose clearance rate. Further studies indicated that LvRTK2 may regulate shrimp growth by modulating the downstream PI3K/AKT signaling pathway and a series of glucose metabolism events, such as glycolysis, gluconeogenesis, glycogen synthesis, and glycogenolysis. This report on the characteristics and functions of LvRTK2 confirms the important role of RTK2-type IRs in regulating shrimp growth and glucose metabolism. [ABSTRACT FROM AUTHOR]

Some respiratory viruses, such as Human Rhinovirus, SARS-CoV-2, and Enterovirus D-68 (EV-D68), share the feature of hijacking host lipids in order to generate specialised replication organelles (ROs) with unique lipid compositions to enable viral replication. We have recently uncovered a novel non-canonical function of the stimulator of interferon genes (STING) pathway, as a critical factor in the formation of ROs in response to HRV infection. The STING pathway is the main DNA virus sensing system of the innate immune system controlling the type I IFN machinery. Although it is well-characterised as part of the DNA sensor machinery, the STING function in RNA viral infections is largely unexplored. In the current study, we investigated whether other RO-forming RNA viruses, such as EV-D68 and SARS-CoV-2, can also utilise STING for their replication. Using genetic and pharmacological inhibition, we demonstrate that STING is hijacked by these viruses and is utilised as part of the viral replication machinery. STING also co-localises with glycolytic enzymes needed to fuel the energy for replication. The inhibition of STING leads to the modulation of glucose metabolism in EV-D68-infected cells, suggesting that it might also manipulate immunometabolism. Therefore, for RO-generating RNA viruses, STING seems to have non-canonical functions in membrane lipid re-modelling, and the formation of replication vesicles, as well as immunometabolism. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the deadly malignant tumors that directly leads to the death of nearly one million people worldwide every year, causing a serious burden on society. In the presence of sufficient oxygen, HCC cells rapidly generate energy through aerobic glycolysis, which promotes tumor cell proliferation, immune evasion, metastasis, angiogenesis, and drug resistance. Pyruvate kinase M2 (PKM2) is a key rate‐limiting enzyme in glycolysis. In recent years, studies have found that PKM2 not only exerts pyruvate kinase activity in the process of glucose metabolism, but also exerts protein kinase activity in non‐metabolic pathways to affect tumor cell processes, and its activity is flexibly regulated by various posttranslational modifications such as acetylation, phosphorylation, lactylation, ubiquitination, SUMOylation, and so forth. This review summarizes the role of posttranslational modifications of PKM2‐related sites in the development of HCC. Summary: Hepatocellular carcinoma (HCC) is one of the deadly malignant tumors.Even in the case of sufficient oxygen, HCC cells rapidly generate energy through aerobic glycolysis.Pyruvate kinase M2 (PKM2) is a key rate‐limiting enzyme in glycolysis.Recent studies have found that the posttranslational modification of PKM2 flexibly regulates its pyruvate kinase activity and protein kinase activity, thus affecting the important physiological functions of cells.This review summarizes the role of posttranslational modifications of PKM2‐related sites in the development of HCC.It has been found that posttranslational modifications of PKM2‐related sites mostly promote the occurrence, metastasis and drug resistance of HCC, often suggesting poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Ketogenic diets are proposed as a therapeutic approach for type 1 and type 2 diabetes due to their low glucose intake. However, their potential effects on the immune system need investigation. This study aims to explore how glucose concentration and beta-hydroxybutyrate (BHB) impact T cell phenotype, metabolism, and function, with a focus on systemic inflammatory response (T2D) and autoimmunity (T1D). Methods: T cells from healthy donors were cultured in vitro under varying glucose concentrations with or without BHB. Flow cytometry was employed to analyze changes in T cell phenotype, while proliferation was evaluated through a CFSE dilution assay. Additionally, we used a novel flow cytometry method allowing a direct assessment of T cell metabolism. Results: Culturing T cells in low glucose concentrations revealed their dependency on glucose metabolism, leading to reduced proliferation rates, overexpression of exhaustion markers and increased susceptibility to Treg suppression and the influence of immune-modulating drugs such as rapamycin, FK506, and MMF. Notably, T cells cultured in low glucose concentrations increased the expression of BDH1 to utilize BHB as an alternative fuel source. Finally, the addition of BHB to the culture effectively rescued T cell impairments caused by insufficient glucose levels. Conclusions: T cells display limited capacity to adapt to low glucose levels, resulting in profound functional impairment. However, T cell functions can be efficiently recovered by the presence of 2mM BHB. [ABSTRACT FROM AUTHOR]

A potential therapeutic approach for cancer treatment is target oxidative phosphorylation and glycolysis simultaneously. The matrix protein of vesicular stomatitis virus (VSV MP) can target the surface of mitochondria, causing morphological changes that may be associated with mitochondrial dysfunction and oxidative phosphorylation inhibition. Previous research has shown that mitochondrial abnormalities can direct glucose metabolism toward glycolysis. Thus, after treatment with VSV MP, glycolysis inhibition is necessary to completely block glucose metabolism and eradicate cancer. Here, to inhibit glycolysis, the 2-deoxy-D-glucose (2-DG), a synthetic glucose analog was used to combine with VSV MP to treat cancer. This study aims to determine how VSV MP affects the glucose bioenergetic metabolism of cancer cells and to evaluate the synergistic effect of 2-DG when combined with VSV. Our results indicated that in U87 and C6 glioblastoma cell lines, VSV MP caused mitochondrial membrane potential loss, cytochrome c release, and glucose bioenergetics metabolism reprogramming. When combined with 2-DG, VSV MP synergistically aggravated cell viability, apoptosis, and G2/M phase arrest. Meanwhile, the combination therapy exacerbated ATP depletion, activated AMPK, and inhibited mammalian target of rapamycin signaling pathways. In addition, 2-DG treatment alone induced autophagy in glioblastoma cells; however, VSV MP inhibited the autophagy induced by 2-DG in combined treatment and finally contributed to the enhanced cytotoxic effect of the combination strategy in U87 and C6 cancer cells. In the orthotopic U87 glioblastoma model and subcutaneous C6 glioblastoma model, the combined treatment led to significant tumor regression and prolonged survival. A potent therapeutic approach for treating glioblastoma may be found in the combination of VSV MP and glycolytic inhibitors. [ABSTRACT FROM AUTHOR]

The agricultural pest Drosophila suzukii exhibits a strong preference for feeding on fresh fruits, demonstrating high adaptability to sugary environments. Meanwhile, high sugar levels stimulate insulin secretion, thereby regulating the steady state of sugar metabolism. Understanding the mechanisms related to sugar metabolism in D. suzukii is crucial due to its adaptation to these specific environmental conditions. The insulin signaling pathway is an evolutionarily conserved phosphorylation cascade with significant roles in development and metabolism. We observed that the activation of the insulin signaling pathway inhibited FoxO activity and downregulated the expression of Pepck, thereby activating glycolysis and reducing glucose levels. By contrast, inhibiting insulin signaling increased the FoxO activity and upregulated the expression of Pepck, which activated gluconeogenesis and led to increased glucose levels. Our findings demonstrated the crucial role of the insulin signaling pathway in mediating glucose metabolism through the FoxO–Pepck axis, which supports the ecological adaptation of D. suzukii to high-sugar niches, thereby providing insights into its metabolic control and suggesting potential strategies for pest management. Elucidating these molecular processes is important for understanding metabolic regulation and ecological specialization in D. suzukii. [ABSTRACT FROM AUTHOR]

The impact of aging on body composition and glucose metabolism is not well established in C57BL/6J mice, despite being a common pre-clinical model for aging and metabolic research. The purpose of this study was to examine the effect of advancing age on body composition, in vivo glucose metabolism, and skeletal muscle AKT expression in young (Y: 4 months old, n = 7), old (O: 17–18 months old, n = 10), and very old (VO: 26–27 month old, n = 9) male C57BL/6J mice. Body composition analysis, assessed by nuclear magnetic resonance, demonstrated O mice had a significantly greater fat mass and body fat percentage when compared to Y and VO mice. Furthermore, VO mice had a significantly greater lean body mass than both O and Y mice. We also found that the VO mice had greater AKT protein levels in skeletal muscle compared to O mice, an observation that explains a portion of the increased lean body mass in VO mice. During glucose tolerance (GT) testing, blood glucose values were significantly lower in the VO mice when compared to the Y and O mice. No age-related differences were observed in insulin tolerance (IT). We also assessed the glucose response to AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). The change in blood glucose following AICAR administration was significantly reduced in VO mice compared to Y and AG mice. Our findings indicate that lean body mass and AKT2 protein expression in muscle are significantly increased in VO mice compared to O mice. The increase in AKT2 likely plays a role in the greater lean body mass observed in the oldest of old mice. Finally, despite the increased GT, VO mice appear to be resistant to AMPK-mediated glucose uptake. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) with the BRAFV600E mutation is associated with a poorer prognosis. BRAF inhibitors may demonstrate limited efficacy due to emerging drug resistance. The Warburg effect may have cancer therapeutic implications. It is not known if the BRAFV600E mutation is associated with altered glucose metabolism in PTC. Methods: This study examined the effect of BRAFV600E and dynamin-related protein 1 (DRP1) on various cellular processes in PTC cells, including cell proliferation, migration, invasion, mitochondrial fission, glucose metabolism, reactive oxygen species (ROS) generation, and apoptosis. We used RT-qPCR to assess the expression of key glycolytic enzymes in thyroid cancer tissues. Additionally, the regulatory interaction between BRAFV600E and DRP1 was investigated through Western blot and immunohistochemical staining. We further evaluated the impact of DRP1 in PTC and the inhibitory effects of dabrafenib and 2-deoxy-d-glucose (2-DG) in vitro and in vivo. Results: We found that the BRAFV600E mutation significantly augments aerobic glycolysis while suppressing oxidative phosphorylation in PTC. We identified the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway as a critical mediator in PTC progression. First, the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway enhances cell proliferation by upregulating hexokinase 2 expression and thereby increasing aerobic glycolysis. Second, it inhibits apoptosis by promoting mitochondrial fission and reducing ROS levels. Moreover, we demonstrated that the combination therapy of 2-DG and dabrafenib markedly impedes the progression of BRAFV600E-positive PTC. Conclusion: The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway plays a pivotal role in glucose metabolism reprogramming, contributing to the aggressiveness and progression of BRAFV600E-positive PTC. Our findings suggest that a combined therapeutic approach using 2-DG and dabrafenib has the potential to improve the outcome of PTC patients with BRAFV600E. [ABSTRACT FROM AUTHOR]

G6PC2 encodes a glucose-6-phosphatase catalytic subunit that opposes the action of glucokinase in pancreatic islets, thereby modulating the sensitivity of insulin and glucagon secretion to glucose. In mice, G6pc2 is expressed at ~20-fold higher levels in ß-cells than in a-cells, whereas in humans G6PC2 is expressed at only ~5-fold higher levels in ß-cells. We therefore hypothesize that G6PC2 likely influences glucagon secretion to a greater degree in humans. With a view to generating a humanized mouse that recapitulates augmented G6PC2 expression levels in a-cells, we sought to identify the genomic regions that confer differential mouse G6pc2 expression in a-cells versus ß-cells as well as the evolutionary changes that have altered this ratio in humans. Studies in islet-derived cell lines suggest that the elevated G6pc2 expression in mouse ß-cells versus a-cells is mainly due to a difference in the relative activity of the proximal G6pc2 promoter in these cell types. Similarly, the smaller difference in G6PC2 expression between a-cells and ß-cells in humans is potentially explained by a change in relative proximal G6PC2 promoter activity. However, we show that both glucocorticoid levels and multiple differences in the relative activity of eight transcriptional enhancers between mice and humans likely contribute to differential G6PC2 expression. Finally, we show that a mouse-specific non-coding RNA, Gm13613, whose expression is controlled by G6pc2 enhancer I, does not regulate G6pc2 expression, indicating that altered expression of Gm13613 in a humanized mouse that contains both the human promoter and enhancers should not affect G6PC2 function. [ABSTRACT FROM AUTHOR]

Objectives: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier‐related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. Materials and Methods: A CAL‐27‐LEC co‐culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability. Western blotting and RT‐qPCR detected protein and mRNA expression under different conditions, respectively. CCK‐8, scratch wound healing, and transwell assays revealed cell migration and proliferation. Tube formation experiment tested capacity for endothelial tube formation. Immunohistochemical staining analyzed tissue sections from 43 oral cancer individuals with/without diabetes. Results: In high‐glucose co‐culture system, we observed increased lymphatic barrier permeability and decreased expression of ZO‐1 and occludin, two tight‐junction proteins; conversely, the expression of PAR2, a high permeability‐related protein, was increased. Following linagliptin treatment, the expression levels of VEGF‐C, VEGFR‐3, and PAR2 decreased, while those of ZO‐1 and occludin increased. Considerably higher levels of LYVE‐1 expression in individuals with diabetes than in those without diabetes. Conclusions: By ameliorating the high glucose‐induced disruption of the lymphatic endothelial barrier, linagliptin may reduce lymphangiogenesis and exhibit an inhibitory effect on lymphatic metastasis in oral cancer patients with diabetes. [ABSTRACT FROM AUTHOR]

Cancer cells change their glucose metabolism towards lactic acid production for various defensive and proliferative advantages. Dichloroacetate (DCA) is an inhibitor of a key enzyme and thus, changes back the OX‐PHOS to glycolysis ratio. We designed and synthesized a singlet oxygen triggered source of dichloroacetate which releases this inhibitor during photodynamic singlet oxygen generation. Synergistic action of DCA and singlet oxygen results in significant enhancement of photocytotoxicity. The results suggest that this approach could offer significant improvement in the therapeutic outcome of PDT. [ABSTRACT FROM AUTHOR]

Objective: To date, there are no widely implemented machine learning (ML) models that predict progression from prediabetes to diabetes. Addressing this knowledge gap would aid in identifying at-risk patients within this heterogeneous population who may benefit from targeted treatment and management in order to preserve glucose metabolism and prevent adverse outcomes. The objective of this study was to utilize readily available laboratory data to train and test the performance of ML-based predictive risk models for progression from prediabetes to diabetes. Methods: The study population was composed of laboratory information services data procured from a large U.S. outpatient laboratory network. The retrospective dataset was composed of 15,029 adults over a 5-year period with initial hemoglobin A1C (A1C) values between 5.0% and 6.4%. ML models were developed using random forest survival methods. The ground truth outcome was progression to A1C values indicative of diabetes (i.e., ≥6.5%) within 5 years. Results: The prediabetes risk classifier model accurately predicted A1C ≥6.5% within 5 years and achieved an area under the receiver-operator characteristic curve of 0.87. The most important predictors of progression from prediabetes to diabetes were initial A1C, initial serum glucose, A1C slope, serum glucose slope, initial HDL, HDL slope, age, and sex. Conclusions: Leveraging readily obtainable laboratory data, our ML risk classifier accurately predicts elevation in A1C associated with progression from prediabetes to diabetes. Although prospective studies are warranted, the results support the clinical utility of the model to improve timely recognition, risk stratification, and optimal management for patients with prediabetes. [ABSTRACT FROM AUTHOR]

The two clathrin isoforms, CHC17 and CHC22, mediate separate intracellular transport routes. CHC17 performs endocytosis and housekeeping membrane traffic in all cells. CHC22, expressed most highly in skeletal muscle, shuttles the glucose transporter GLUT4 from the ERGIC (endoplasmic-reticulum-to-Golgi intermediate compartment) directly to an intracellular GLUT4 storage compartment (GSC), from where GLUT4 can be mobilized to the plasma membrane by insulin. Here, molecular determinants distinguishing CHC22 from CHC17 trafficking are defined. We show that the C-terminal trimerization domain of CHC22 interacts with SNX5, which also binds the ERGIC tether p115. SNX5, and the functionally redundant SNX6, are required for CHC22 localization independently of their participation in the endosomal ESCPE-1 complex. In tandem, an isoform-specific patch in the CHC22 N-terminal domain separately mediates binding to p115. This dual mode of clathrin recruitment, involving interactions at both N- and C-termini of the heavy chain, is required for CHC22 targeting to ERGIC membranes to mediate the Golgi-bypass route for GLUT4 trafficking. Interference with either interaction inhibits GLUT4 targeting to the GSC, defining a bipartite mechanism regulating a key pathway in human glucose metabolism. Synopsis: The formation of insulin-sensitive GLUT4-containing compartments involves direct secretion that bypasses the Golgi apparatus and uses the dedicated clathrin isoform CHC22. This study defines two key interactions between CHC22 and the early secretory tether p115 in this process; direct binding by the CHC22 N-terminal domain and indirectly through SNX5/6 bound to the CHC22 trimerization domain. Sorting nexin 5/6 (SNX5/6) levels influence CHC22 clathrin's membrane localization. SNX5 binds the early secretory pathway protein p115. The terminal domain (TD) of CHC22 clathrin contains an isoform-specific divergent patch that binds p115. CHC22 direct binding to p115 via the TD and binding to SNX5/6 are required for association with the early secretory pathway. The two-site interaction of CHC22 with p115 is required for appropriate trafficking of the insulin-responsive glucose transporter GLUT4. Insulin-responsive GLUT4 secretion requires a designated clathrin isoform, CHC22, which is specifically recruited through its interactions with the trafficking proteins p115 and SNX5. [ABSTRACT FROM AUTHOR]

Introduction: Amyloid-β (Aβ) plaques is a significant hallmark of Alzheimer's disease (AD), detectable via amyloid-PET imaging. The Fluorine-18-Fluorodeoxyglucose ([18F]FDG) PET scan tracks cerebral glucose metabolism, correlated with synaptic dysfunction and disease progression and is complementary for AD diagnosis. Dual-scan acquisitions of amyloid PET allows the possibility to use early-phase amyloid-PET as a biomarker for neurodegeneration, proven to have a good correlation to [18F]FDG PET. The aim of this study was to evaluate the added value of synthesizing the later from the former through deep learning (DL), aiming at reducing the number of PET scans, radiation dose, and discomfort to patients. Methods: A total of 166 subjects including cognitively unimpaired individuals (N = 72), subjects with mild cognitive impairment (N = 73) and dementia (N = 21) were included in this study. All underwent T1-weighted MRI, dual-phase amyloid PET scans using either Fluorine-18 Florbetapir ([18F]FBP) or Fluorine-18 Flutemetamol ([18F]FMM), and an [18F]FDG PET scan. Two transformer-based DL models called SwinUNETR were trained separately to synthesize the [18F]FDG from early phase [18F]FBP and [18F]FMM (eFBP/eFMM). A clinical similarity score (1: no similarity to 3: similar) was assessed to compare the imaging information obtained by synthesized [18F]FDG as well as eFBP/eFMM to actual [18F]FDG. Quantitative evaluations include region wise correlation and single-subject voxel-wise analyses in comparison with a reference [18F]FDG PET healthy control database. Dice coefficients were calculated to quantify the whole-brain spatial overlap between hypometabolic ([18F]FDG PET) and hypoperfused (eFBP/eFMM) binary maps at the single-subject level as well as between [18F]FDG PET and synthetic [18F]FDG PET hypometabolic binary maps. Results: The clinical evaluation showed that, in comparison to eFBP/eFMM (average of clinical similarity score (CSS) = 1.53), the synthetic [18F]FDG images are quite similar to the actual [18F]FDG images (average of CSS = 2.7) in terms of preserving clinically relevant uptake patterns. The single-subject voxel-wise analyses showed that at the group level, the Dice scores improved by around 13% and 5% when using the DL approach for eFBP and eFMM, respectively. The correlation analysis results indicated a relatively strong correlation between eFBP/eFMM and [18F]FDG (eFBP: slope = 0.77, R2 = 0.61, P-value < 0.0001); eFMM: slope = 0.77, R2 = 0.61, P-value < 0.0001). This correlation improved for synthetic [18F]FDG (synthetic [18F]FDG generated from eFBP (slope = 1.00, R2 = 0.68, P-value < 0.0001), eFMM (slope = 0.93, R2 = 0.72, P-value < 0.0001)). Conclusion: We proposed a DL model for generating the [18F]FDG from eFBP/eFMM PET images. This method may be used as an alternative for multiple radiotracer scanning in research and clinical settings allowing to adopt the currently validated [18F]FDG PET normal reference databases for data analysis. [ABSTRACT FROM AUTHOR]