The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis

Journal of Clinical and Translational Hepatology, Journal Year: 2025, Volume and Issue: 000(000), P. 000 - 000

Published: Jan. 22, 2025

Solute carrier (SLC) family transporters are crucial transmembrane proteins responsible for transporting various molecules, including amino acids, electrolytes, fatty and nucleotides. To date, more than fifty SLC transporter subfamilies have been identified, many of which linked to the progression hepatic steatosis fibrosis. These conditions often caused by factors such as non-alcoholic liver disease steatohepatitis, major contributors global burden. The activity members regulates transport substrates across biological membranes, playing key roles in lipid synthesis metabolism, mitochondrial function, ferroptosis. processes, turn, influence function hepatocytes, stellate cells, macrophages, thereby contributing development Additionally, some involved drug transport, acting critical regulators drug-induced steatosis. Beyond substrate certain also exhibit additional functions. Given pivotal role fibrosis, this review aimed summarize molecular mechanisms through these conditions.

Language: Английский

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γ-Glutamylcysteine suppresses epithelial-mesenchymal transition in lens epithelial cells to ameliorate diabetic cataract through regulating TGF-β2 and AMPK-related signaling pathways

Journal of Functional Foods, Journal Year: 2025, Volume and Issue: 127, P. 106725 - 106725

Published: March 14, 2025

Language: Английский

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Exogenous Nucleotides Ameliorate Insulin Resistance Induced by Palmitic Acid in HepG2 Cells through the IRS-1/AKT/FOXO1 Pathways

Nutrients, Journal Year: 2024, Volume and Issue: 16(12), P. 1801 - 1801

Published: June 7, 2024

Nucleotides (NTs) act as pivotal regulatory factors in numerous biological processes, playing indispensable roles growth, development, and metabolism across organisms. This study delves into the effects of exogenous NTs on hepatic insulin resistance using palmitic-acid-induced HepG2 cells, administering interventions at three distinct dosage levels NTs. The findings underscore that NT intervention augments glucose consumption modulates expression glycogen-synthesis-related enzymes (glycogen synthase kinase 3β glycogen synthase), influences content. Additionally, it governs (hexokinase, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase). Moreover, orchestrates signaling pathway (insulin receptor substrate-1, protein B, forkhead box O1) AMP-activated (AMPK) activity cells. Furthermore, fine-tunes oxidative stress-related markers (malondialdehyde, glutathione peroxidase, NADPH oxidase 4) inflammation-related nuclear transcription factor (NF-κB). Lastly, regulates transporter proteins (GLUTs). Consequently, ameliorate cells by modulating IRS-1/AKT/FOXO1 pathways regulate consumption, content, pathways, AMPK activity, stress, inflammatory status.

Language: Английский

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Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies)

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 13759 - 13759

Published: Sept. 6, 2023

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as promising approach for the treatment its complications. Kiwifruit recognized substantial content antioxidative phenolics. Therefore, this work aimed to examine effect Actinidia deliciosa (kiwi fruit) on hepatorenal damage in high-fat diet (HFD) streptozotocin (STZ)-induced T2D rats using vivo silico analyses. An increase hepatic renal lipid peroxidation was observed diabetic accompanied by decrease antioxidant status. Furthermore, it important highlight that there were observable inflammatory apoptotic responses organs diabetes, along dysregulation phosphorylation levels mammalian target rapamycin (mTOR), protein kinase B (Akt), phosphoinositide 3-kinase (PI3K) signaling proteins. However, administration kiwi extract alleviated dysfunction, processes, injury, events activation pathway. molecular docking dynamic simulation studies revealed quercetin, chlorogenic acid, melezitose components docked well potential effective natural products activating silent information regulator 1(SIRT-1) phenolic acids extract, especially syringic P-coumaric caffeic ferulic have ability inhibit phosphatase tensin homolog (PTEN) active site. In conclusion, can be argued may present potentially beneficial adjunctive

Language: Английский

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LC-MS-Based Metabolomics Reveals the Mechanism of Protection of Berberine against Indomethacin-Induced Gastric Injury in Rats

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1055 - 1055

Published: Feb. 28, 2024

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in wide variety of medicinal plants. has been demonstrated to exhibit potent prevention indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for first time investigate alteration serum metabolites protection berberine against rats. Subsequently, bioinformatics utilized analyze potential metabolic pathway anti-GI effect berberine. The pharmacodynamic data indicated that could ameliorate pathological damage, inhibit level proinflammatory factors serum, and increase antioxidant serum. LC-MS-based analysis conducted this study presence 57 differential rats induced GI caused by indomethacin, associated 29 pathways. Moreover, revealed showed significant impact on metabolites, 45 being reported between model group treated were 24 pathways, administration regulated 14 affecting primary pathways affected glutathione metabolism arachidonic acid metabolism. Based results, it can be concluded gastroprotective GI. This particularly since elucidate berberine’s action results suggest may energy metabolism, oxidative stress, inflammation regulation. These findings pave way development new therapeutic interventions management NSAID-induced disorders.

Language: Английский

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Current Advances in the Salt Reduction Properties of Kokumi γ-Glutamyl Peptides: A Review

Food Reviews International, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Oct. 8, 2024

A high-salt diet poses potential risks to human health. The current use of sodium substitutes in the food industry often results a reduction organoleptic quality food. γ-Glutamyl peptides are small-molecule containing γ-glutamyl residues, which significantly contribute kokumi taste foods. These exhibit synergistic effect when consumed with salt, thereby enhancing perception saltiness and aiding prevention various cardiovascular diseases associated excessive salt intake. have garnered considerable attention from researchers for their role eliciting inducing biological activities through activation calcium-sensing receptor (CaSR). This paper provides comprehensive review dietary sources, efficient preparations, taste-enhancing properties, evaluation methods, peptides. study aims explore application industry. Additionally, it offers theoretical foundation reference in-depth "salt without reducing saltiness", development related functional products.

Language: Английский

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Flavonoids from Lophatherum gracile Brongn. Ameliorate Liver Damages in High-Fat Diet and Streptozotocin-Induced Diabetic Mice by Regulating PI3K/AKT and NF-Kappa B Pathways

Journal of Food Biochemistry, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 16

Published: Oct. 6, 2023

Inflammation and metabolic disorders are crucial factors that induce type 2 diabetes mellitus (T2DM). Lophatherum gracile Brongn. (L. gracile) has been popularly consumed as folk medicine dietary supplement for the treatment of fever inflammatory-associated diseases. Flavonoids major constituents L. with various pharmacological effects. However, protective effects flavonoids from leaves against T2DM, well potential mechanisms, were not yet elucidated. In present study, total flavonoid content (LGBF) higher pancreas lipase inhibitory activity was extracted screened gracile. Twelve compounds identified in LGBF by liquid LC-MS analysis. Network pharmacology seven 10 core targets associated T2DM. GO KEGG pathway enrichment analysis indicated PI3K/AKT inflammation-related pathways might occupy status. Molecular docking results showed active had a good binding key targets. Furthermore, high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice developed treated experimental validation. The data intervention potently improved lipid profiles insulin sensitivity HFD STZ-induced mice. Hepatic inflammation accumulation also partially reversed intervention. Further assays confirmed administration significantly increased PI3K AKT phosphorylation, while reducing IL-1β expression NF-κB P65 phosphorylation liver conclusion, could relieve damage via regulating pathways.

Language: Английский

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Biosynthesis of the antioxidant γ‐glutamyl‐cysteine with engineered Yarrowia lipolytica

Biotechnology Journal, Journal Year: 2024, Volume and Issue: 19(2)

Published: Feb. 1, 2024

The dipeptide γ-glutamylcysteine (γ-GC), the first intermediate of glutathione (GSH) synthesis, is considered as a promising drug to reduce or prevent plethora age-related disorders such Alzheimer and Parkinson diseases. unusual γ-linkage between two constitutive amino acids, namely cysteine glutamate, renders its chemical synthesis particularly challenging. Herein, we report on metabolic engineering non-conventional yeast Yarrowia lipolytica for efficient γ-GC synthesis. was converted into producer by disruption gene GSH2 encoding GSH synthase expression GSH1 glutamylcysteine ligase. Subsequently genes involved in glutamate anabolism, MET4, CYSE, CYSF, GDH1 were overexpressed with aim increase their intracellular availability. With strategy, titer 464 nmol mg

Language: Английский

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γ‐Glutamylcysteine Ameliorates LPS‐Induced Inflammatory Responses in BV2 Cells via Activating Autophagy

Journal of Food Biochemistry, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

In neurodegenerative diseases, the activation of microglia and ensuing neuroinflammation are pivotal in regulating disease progression. Attenuating inflammation induced by microglial cells is considered a key strategy for slowing progression diseases. γ‐glutamylcysteine (γ‐GC) has exhibited significant antioxidative anti‐inflammatory effects; nevertheless, its potential role modulating neuroinflammatory responses remains incompletely explored. The current investigation aimed to establish model stimulating BV2 with lipopolysaccharide (LPS) explore protective effect γ‐GC on cells. results demonstrated that significantly attenuated LPS‐induced oxidative damage cells, reduced levels tumor necrosis factor‐α (TNF‐α) interleukin‐1β (IL‐1β), inhibited cytoplasmic translocation high‐mobility group box 1 protein (HMGB1), effectively mitigated inflammatory response We further investigated regulatory mechanism found enhances autophagy resulting marked reduction mammalian target rapamycin (mTOR) phosphorylation an increase AMP‐activated kinase (AMPK) levels. use inhibitors 3‐methyladenine (3‐MA) AMPK corroborates proposition promotes while suppressing through AMPK‐mTOR pathway. findings indicate exerts substantial inhibitory impact neuroinflammation, making it promising candidate development therapeutic strategies against disorders related conditions.

Language: Английский

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γ‐Glutamylcysteine Inhibits VSMC‐Derived Foam Cell Formation via Upregulating Thioredoxin‐1 Expression

Journal of Food Biochemistry, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

The formation and accumulation of foam cells within the arterial wall is main early event atherosclerosis. Vascular smooth muscle (VSMCs) are most abundant in human atherosclerotic lesions suggested to contribute atheroma cells. γ ‐glutamylcysteine ( ‐GC), as an immediate precursor glutathione, exhibits anti‐inflammatory antioxidant effects. However, effects ‐GC on plaques not yet clarified. Here, we display against ox‐LDL‐induced foamy VSMCs. Our results showed that apparently reduced total intracellular cholesterol content mouse rat oil red O fluorescent BODIPY staining indicated inhibited cell. Mechanistically, expression macrophage scavenger receptor 1 (Msr1) VSMCs attenuate uptake by Further RNA‐seq analysis, immunofluorescence well immunoblotting measurements thioredoxin‐1 (Txn1) was important for reduce Msr1 lipid Overall, our research increases Txn1 expression, which causes A reduction inhibition ox‐LDL‐stimulated study revealed has potential prevention

Language: Английский

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