Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice DOI Creative Commons
Ann Wells, John J. Wilson, Sarah E. Heuer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 25, 2023

Abstract Objective Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), COVID-19, but the effects 2DG on gene function across different tissues are unclear. Methods This study analyzed transcriptional profiles nine from C57BL/6J mice treated with to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted co-network (WGCNA), variance, pathway were all performed identify modules altered by treatment. Results PCA revealed that samples clustered predominantly tissue, suggesting affects each tissue uniquely. Unsupervised clustering WGCNA six distinct tissue-specific significantly affected 2DG, unique key genes. mitochondrial metabolism in heart, while small intestine, immunological pathways. Conclusions These findings suggest impact varies organs, potentially affecting multiple functions. The provides insights into diseases highlights importance understanding its future research clinical applications.

Language: Английский

Metabolomic Investigation of Brain and Liver in Rats Fed Docosahexaenoic Acid in Regio‐ and Enantiopure Triacylglycerols DOI Creative Commons
Raghunath Pariyani, Yumei Zhang, Guđmundur G. Haraldsson

et al.

Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: 68(5)

Published: Feb. 23, 2024

Scope N‐3 polyunsaturated fatty acids (n‐3 PUFAs) play important roles in cognitive functions. However, there is a lack of knowledge on the metabolic impact regio‐ and stereo‐specific positioning n‐3 PUFAs dietary triacylglycerols. Methods results Rats state mild PUFA deficiency are fed daily with 360 mg triacylglycerols containing DHA (docosahexaenoic acid) at sn (stereospecific numbering)‐1, 2, or 3 positions 18:0 remaining positions, an equal amount tristearin for 5 days. Groups deficient diet normal adequate included as controls. The profiles brain liver studied using NMR (nuclear magnetic resonance)‐based metabolomics. Several metabolites significance membrane integrity neurotransmission, glutamate, particular, significantly lower groups ‐1 ‐3 compared to ‐2 group. Further, show lactate level diet, suggesting prominent role C18:0 regulating energy metabolism. Conclusion This study sheds light stereospecific stearic acid metabolism liver.

Language: Английский

Citations

3
Glycolytic enzymes in non-glycolytic web: functional analysis of the key players DOI

Avirup Malla,

Suvroma Gupta, Runa Sur

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(2), P. 351 - 378

Published: Jan. 9, 2024

Language: Английский

Citations

2
Time-resolved map of serum metabolome profiling in D-galactose-induced aging rats with exercise intervention DOI Creative Commons
Xue Li, Changling Wei, Jin Yu

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 108999 - 108999

Published: Jan. 26, 2024

Exercise, an intervention with wide-ranging effects on the whole body, has been shown to delay aging. Due aging and exercise as modulator of metabolism, a picture how delayed D-galactose (D-gal)-induced in time-resolved manner was presented this paper. The mapping molecular changes response become increasingly accessible development omics techniques. To explore dynamic during exercise, serum rats D-gal-induced before, during, after analyzed by untargeted metabolomics. variation metabolites monitored reveal specific senescence multiple pathways, especially basal amino acid including glycine serine threonine cysteine methionine tryptophan metabolism. homeostasis disturbed D-gal maintained exercise. paper expected provide theoretical basis for study anti-aging

Language: Английский

Citations

1
Quantitative proteomic analysis of oxaliplatin induced peripheral neurotoxicity DOI
Linlin Yang, Hua Wang,

Wanting Lu

et al.

Journal of Proteomics, Journal Year: 2022, Volume and Issue: 266, P. 104682 - 104682

Published: July 10, 2022

Language: Английский

Citations

4
Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice DOI Creative Commons
Ann Wells, John J. Wilson, Sarah E. Heuer

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(3), P. e0299595 - e0299595

Published: March 7, 2024

Objective Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), COVID-19, but the effects 2DG on gene function across different tissues are unclear. Methods This study analyzed transcriptional profiles nine from C57BL/6J mice treated with to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted co-network (WGCNA), variance, pathway were all performed identify modules altered by treatment. Results PCA revealed that samples clustered predominantly tissue, suggesting affects each tissue uniquely. Unsupervised clustering WGCNA six distinct tissue-specific significantly affected 2DG, unique key genes. mitochondrial metabolism in heart, while small intestine, immunological pathways. Conclusions These findings suggest impact varies organs, potentially affecting multiple functions. The provides insights into diseases highlights importance understanding its future research clinical applications.

Language: Английский

Citations

0
Cardiometabolic state links neurovascular burden with brain structure and function across age: evidence from EEG and MRI DOI Creative Commons

Daniel Franco-O’Byrne,

Ana María Castro Laguardia, Carolina Delgado

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Abstract Aging affects brain structure and function alongside metabolic vascular processes leading to energetic impairments. While local neurometabolic dysfunction in aging is well-documented, the influence of systemic cardiometabolic markers on remains less understood. We examine link between (measured by an allostatic load index) neurovascular burden white matter hyperintensities) with changes, including ventricular hippocampal volume, as well EEG activity, across age. Analyzing data from 196 healthy individuals age (20-75 years), we found a significant positive correlation index white-matter hyperintensities, irrespective White-matter hyperintensities are also positively linked enlargement, but not atrophy. The mediated relationship volume. Regarding function, changes spectral aperiodic exponent periodic alpha power were index. Such hyperintensities. Thus, findings suggest that state, measured index, plays crucial role health age, particularly influencing enlargement increased activity.

Language: Английский

Citations

0
Mass Spectrometry Imaging Reveals Spatial Metabolic Alterations and Salidroside’s Effects in Diabetic Encephalopathy DOI Creative Commons
Shuohan Cheng,

Xianyue Meng,

Zixuan Wang

et al.

Metabolites, Journal Year: 2024, Volume and Issue: 14(12), P. 670 - 670

Published: Dec. 2, 2024

Background: Diabetic encephalopathy (DE) is a neurological complication of diabetes marked by cognitive decline and complex metabolic disturbances. Salidroside (SAL), natural compound with antioxidant neuroprotective properties, has shown promise in alleviating diabetic complications. Exploring the spatial reprogramming DE elucidating SAL’s effects are critical for deepening our understanding its pathogenesis developing effective therapeutic strategies. Methods: Air-flow-assisted desorption electrospray ionization–mass spectrometry imaging (AFADESI-MSI) was employed to investigate alterations brains db/db mice, spontaneous model. The mice were treated SAL (30 150 mg/kg, orally) 12 weeks. Differential metabolites identified characterized using high-resolution mass validated against public databases. Results: Our AFADESI-MSI analysis revealed significant changes 26 compared controls. These indicated disruptions glucose, glutamate-glutamine, nucleotide, lipid, choline, aspartate, L-carnitine metabolism. Notably, glucose 6-phosphate (G6P), glutamine, adenosine, L-carnitine, choline exhibited similar trends both STZ-induced rat models DE, suggesting their potential as reliable biomarkers. Twelve weeks treatment demonstrated positive regulatory effect on metabolism, glutamate–glutamine cycle, lipid Conclusions: This study identifies key demonstrates modulating these disturbances, offering valuable insights targeted interventions

Language: Английский

Citations

0
Metabolic correction of neurodegenerative pathologies: the role of macronutrients and timing DOI Creative Commons
Yuri Zilberter,

Tanya Zilberter

Exploration of neuroscience, Journal Year: 2023, Volume and Issue: unknown, P. 67 - 81

Published: April 21, 2023

Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s Parkinson’s acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state most, if not all, risk factors preceding onset major NDDs. proposes initial brain resulting specifically from hyperactivation nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline utilization primary initiating factor The existing clinical experimental evidence points to NOX as mechanism shared within During stress, activation triggered variable cells via multiple pathways, beta-amyloid alpha-synuclein, fibrin glutamate seizures. Therefore, strategy should have targeted NOX, wouldn’t there be lack clinically approved selective antagonists? On other hand, are promising metabolism-altering approaches dietary means able switch energy intake ketones, which influences both could ameliorate disease progression. regimen time-restricted eating appears most feasible, nutritious, palatable one providing essential benefits ketogenic diet without adverse effects.

Language: Английский

Citations

0
Transcriptome Analysis Reveals Organ-Specific Effects of 2-Deoxyglucose Treatment in Healthy Mice DOI Creative Commons
Ann Wells, John J. Wilson, Sarah E. Heuer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 25, 2023

Abstract Objective Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), COVID-19, but the effects 2DG on gene function across different tissues are unclear. Methods This study analyzed transcriptional profiles nine from C57BL/6J mice treated with to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted co-network (WGCNA), variance, pathway were all performed identify modules altered by treatment. Results PCA revealed that samples clustered predominantly tissue, suggesting affects each tissue uniquely. Unsupervised clustering WGCNA six distinct tissue-specific significantly affected 2DG, unique key genes. mitochondrial metabolism in heart, while small intestine, immunological pathways. Conclusions These findings suggest impact varies organs, potentially affecting multiple functions. The provides insights into diseases highlights importance understanding its future research clinical applications.

Language: Английский

Citations

0