Pleozymes: Pleiotropic Oxidized Carbon Nanozymes Enhance Cellular Metabolic Flexibility DOI Creative Commons
Anh Tran Tram Vo, K. Chandra Mouli, Anton V. Liopo

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(24), P. 2017 - 2017

Published: Dec. 15, 2024

Our group has synthesized a pleiotropic synthetic nanozyme redox mediator we term “pleozyme” that displays multiple enzymatic characteristics, including acting as superoxide dismutase mimetic, oxidizing NADH to NAD+, and H2S polysulfides thiosulfate. Benefits have been seen in acute chronic neurological disease models. The molecule is sourced from coconut-derived activated charcoal undergone harsh oxidization with fuming nitric acid, which alters the structure chemical yielding 3–8 nm discs broad potential. Prior work showed pleozymes localize mitochondria increase oxidative phosphorylation glycolysis. Here, measured cellular NAD+ levels after pleozyme treatment observed increased total but not levels. A 13C-glucose metabolic flux analysis suggested stimulate generation of pyruvate lactate glycolytically tricarboxylic acid (TCA) cycle, pointing malate decarboxylation. Analysis intracellular fatty abundances suggests β-oxidation, concomitant succinyl- acetyl-CoA. Pleozymes ATP, potentially via flexible enhancement NAD+-dependent catabolic pathways such glycolysis, through TCA cycle. These effects may be favorable for pathologies compromise metabolism brain injury.

Language: Английский

Targeting lipid metabolism in regulatory T cells for enhancing cancer immunotherapy DOI Creative Commons
Yang Liu, Xingyue Wang,

Shu‐Rong Wang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189259 - 189259

Published: Jan. 1, 2025

As immunosuppressive cells, Regulatory T cells (Tregs) exert their influence on tumor immune escape within the microenvironment (TME) by effectively suppressing activity of other thereby significantly impeding anti-tumor response. In recent years, metabolic characteristics Tregs have become a focus research, especially important role lipid metabolism in maintaining function Tregs. Consequently, targeted interventions aimed at modulating been recognized as an innovative and promising approach to enhance effectiveness immunotherapy. This review presents comprehensive overview pivotal regulating Tregs, with specific targeting augment responses. Furthermore, we discuss potential opportunities challenges associated this strategy, aiming provide novel insights for enhancing efficacy cancer

Language: Английский

Citations

2
Increased hepatic gluconeogenesis and type 2 diabetes mellitus DOI
Emma Barroso,

Javier Jurado-Aguilar,

Walter Wahli

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(12), P. 1062 - 1077

Published: May 29, 2024

Language: Английский

Citations

9
A hierarchical hepatic de novo lipogenesis substrate supply network utilizing pyruvate, acetate, and ketones DOI
Adam J. Rauckhorst, Ryan D. Sheldon, Daniel J. Pape

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

6
The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications DOI Creative Commons

Jiangxia Du,

Minhui Shen, Jiajia Chen

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Carbohydrates, lipids, bile acids, various inorganic salt ions and organic acids are the main nutrients or indispensable components of human body. Dysregulation in processes absorption, transport, metabolism, excretion these metabolites can lead to onset severe metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, gout hyperbilirubinemia. As second largest membrane receptor supergroup, several major families solute carrier (SLC) supergroup have been found play key roles transport substances carbohydrates, urate, monocarboxylates zinc ions. Based on common dysregulation related substances, we explored relationship between SLC diseases, providing examples drugs targeting proteins that approved currently clinical/preclinical research well SLC-related diagnostic techniques clinical use under investigation. By highlighting connections, aim provide insights may contribute development improved treatment strategies targeted therapies for disorders.

Language: Английский

Citations

0
The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation DOI Creative Commons
Kieran Smith, Kaitlyn M. J. H. Dennis, Leanne Hodson

et al.

Experimental Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract In health, the liver is a metabolically flexible organ that plays key role in regulating systemic lipid and glucose concentrations. There constant flux of fatty acids (FAs) to from multiple sources, including adipose tissue, dietary, endogenously synthesized non‐lipid precursors, intrahepatic droplets recycling triglyceride‐rich remnants. Within liver, FAs are used for triglyceride synthesis, which can be oxidized, stored or secreted very low‐density lipoproteins into circulation. The processes FA uptake, synthesis intracellular partitioning storage, oxidation secretory pathways tightly regulated. An imbalance these causes accumulate associated with development metabolic dysfunction‐associated steatotic disease. It well appreciated many factors influence partitioning, although there good evidence both phenotype (e.g., sex, ethnicity adiposity) dietary macronutrient composition play accumulation, their interaction remains poorly understood. aim this review explore how respective delivery, disposal altered by understand might vivo, humans.

Language: Английский

Citations

0
Natural products targeting AMPK signaling pathway therapy, diabetes mellitus and its complications DOI Creative Commons
Min Li,

Lu Ding,

L. Cao

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Diabetes mellitus (DM) ranks among the most prevalent chronic metabolic diseases, characterized primarily by a persistent elevation in blood glucose levels. This condition typically stems from either insufficient insulin secretion or functional defect itself. Clinically, diabetes is classified into type 1 (T1DM) and 2 (T2DM), with T2DM comprising nearly 90% of all diagnosed cases. Notably, global incidence has surged dramatically over recent decades. The adenylate-activated protein kinase (AMPK) signaling pathway crucial regulating cellular energy metabolism, marking it as significant therapeutic target for related complications. Natural products, their diverse origins, multifaceted bioactivities, relative safety, hold considerable promise modulating AMPK pathway. review article explores advances research on natural products that pathway, aiming to inform development innovative antidiabetic therapies.

Language: Английский

Citations

0
Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics DOI Creative Commons
Kristýna Brejchová, Michal Rahm, Andrea Beňová

et al.

Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 156157 - 156157

Published: Feb. 1, 2025

Highlights•MSDC-0602K differentially affects BM-MSCs and AT-MSCs.•Bioorthogonal click chemistry allowed measurement of pyruvate pools.•Subcellular metabolic flux analysis revealed rewiring pathways.•Metabolic TG synthesis showed distinct adipogenic strategies.AbstractObjectiveInsulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, the mechanisms underlying these side effects remain largely unclear. Here, we investigated different a series thiazolidinediones, including rosiglitazone, pioglitazone, second-generation compound MSDC-0602 K, on human mesenchymal stem cells (MSCs).MethodsWe developed 13C subcellular metabolomic tracer measuring separate mitochondrial cytosolic metabolite pools, lipidomic network-based isotopologue models, bioorthogonal chemistry, to demonstrate that K affected marrow-derived MSCs (BM-MSCs) adipose tissue-derived (AT-MSCs). In BM-MSCs, promoted osteoblastic differentiation suppressed adipogenesis. This effect was clearly from earlier drugs AT-MSCs.ResultsFluxomic data reveal unexpected differences between this drug's provide mechanistic insight into pharmacologic inhibition carrier 1 (MPC). Our study demonstrates retains capacity inhibit MPC, akin rosiglitazone but unlike enabling utilization alternative pathways. Notably, exhibits limited lipogenic potential compared both each which employs strategy.ConclusionsThese findings indicate new-generation do not compromise structure, offering safer for treating insulin resistance. Moreover, results highlight ability cell compartment-specific labeling by reactions metabolomics complex lipids discover molecular within intersection carbohydrate lipid metabolism.Graphical abstract

Language: Английский

Citations

0
sRecirculating aquaculture-fasting strategy (RAS F) to modulate gut microbiota and enhance the fish meat quality of bighead carp (Aristichthys nobilis) DOI

Weifa Su,

Xini Wang,

Weichao Bu

et al.

Food Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 143946 - 143946

Published: March 1, 2025

Language: Английский

Citations

0
Bioinformatic analysis of glycolysis and lactate metabolism genes in head and neck squamous cell carcinoma DOI Creative Commons

Huanyu Jiang,

Lijuan Zhou, Haidong Zhang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 28, 2025

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous cancer with significant global incidence. This study investigates glycolysis- lactate metabolism-related genes (GALMRGs) in HNSCC, focusing on their impact prognosis, the tumor immune microenvironment, potential as therapeutic biomarkers. Analysis of data from Cancer Genome Atlas Gene Expression Omnibus identified 16 GALMRGs that were differentially expressed HNSCC compared to normal tissues. Functional analysis revealed involvement pyruvate metabolism HIF-1 signaling pathways. Weighted gene co-expression network two module genes, CDKN3 SLC2A1. Five key (CAV1, CDKN3, LDHA, MB, PER2) through univariate, multivariate, LASSO regression analyses used construct prognostic model. model demonstrated strong predictive accuracy for overall survival, stratifying patients into high- low-risk groups. Immune infiltration showed negative correlation between resting activated mast cells, had higher mutational burden, suggesting better response immunotherapy. Consensus clustering classified distinct molecular subtypes differing expression genes. GALMRG-based promising biomarker predicting outcomes immunotherapy responses, providing valuable insights personalized treatment strategies.

Language: Английский

Citations

0
FTZ alleviates lipid deposition in diabetic kidney disease by AMPK/ACC/SREBP signaling pathway DOI
Jie Tao, Xiaoyu Zhang, Haibo Tan

et al.

Acta Diabetologica, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0