Mitochondrial folate metabolism–mediated α-linolenic acid exhaustion masks liver fibrosis resolution

Gao, Yanjie; Zheng, Bo; Xu, Shuaiqi; Zhang, Zhibo; Liu, Wanyue; Wang, Tingyu; Yuan, Manman; Sun, Xun; Tan, Yang; Xu, Qiang; Wu, Xingxin

doi:10.1016/j.jbc.2023.104909

Cited by 7 publications

(5 citation statements)

References 54 publications

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“…Collagen I and α-SMA are molecular markers of HSC activation. 4 EGT eliminated the TGFβ1-stimulated upregulation of these two factors (Fig. 1C and D).…”

Section: Resultsmentioning

confidence: 78%

“…3 Under some pathological conditions, contents of profibrotic cytokines in the liver such as transforming growth factor β1 (TGFβ1) are increased, which trigger HSC activation and promote LF occurrence. 4 Smad7 is an inhibitor of the signal transduction downstream of TGFβ1. 5 Upregulated Smad7 in HSCs is beneficial in reducing HSC activation and ameliorating LF.…”

Section: Introductionmentioning

confidence: 99%

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Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Shu,

Lei,

et al. 2023

Food Funct.

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“…Collagen I and α-SMA are molecular markers of HSC activation. 4 EGT eliminated the TGFβ1-stimulated upregulation of these two factors (Fig. 1C and D).…”

Section: Resultsmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Shu,

Lei,

et al. 2023

Food Funct.

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“…7-Aminocarboxycoumarin 2 (7ACC2) is an inhibitor of mitochondrial pyruvate carrier and was used as an alternative inhibitor of mitochondrial pyruvate transport and pyruvate cycling ( 27 , 39 ). LY345899 (LY) is an inhibitor of methylenetetrahydrofolate dehydrogenase 1, a cytosolic NADP + -reducing enzyme in the folate cycle ( 40 – 42 ). As expected, these data show that glucose-stimulated NADP + reduction was blocked with 7ACC2-induced inhibition of pyruvate cycling and not blocked with LY-induced inhibition of folate cycling.…”

Section: Resultsmentioning

confidence: 99%

Apollo-NADP ⁺ reveals in vivo adaptation of NADPH/NADP ⁺ metabolism in electrically activated pancreatic β cells

Bui,

Boswell,

Ciruna

et al. 2023

Sci. Adv.

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Several genetically encoded sensors have been developed to study live cell NADPH/NADP + dynamics, but their use has been predominantly in vitro. Here, we developed an in vivo assay using the Apollo-NADP + sensor and microfluidic devices to measure endogenous NADPH/NADP + dynamics in the pancreatic β cells of live zebrafish embryos. Flux through the pentose phosphate pathway, the main source of NADPH in many cell types, has been reported to be low in β cells. Thus, it is unclear how these cells compensate to meet NADPH demands. Using our assay, we show that pyruvate cycling is the main source of NADP + reduction in β cells, with contributions from folate cycling after acute electrical activation. INS1E β cells also showed a stress-induced increase in folate cycling and further suggested that this cycling requires both increased glycolytic intermediates and cytosolic NAD + . Overall, we show in vivo application of the Apollo-NADP + sensor and reveal that β cells are capable of adapting NADPH/NADP + redox during stress.

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“…Folate was superior to other donors in ameliorating disorders of hepatic one-carbon metabolism in high-fat-fed MAFLD mice and exhibited anti-steatosis and insulin-sensitizing effects [174][175][176][177]. In addition, folate shifted to mitochondrial and consumed α-linolenic acid to maintain TGFβ1 signaling, thereby promoting HSCs activation-mediated hepatic fibrosis in MAFLD [178]. Low vitamin B 12 levels promote lipogenesis and inhibit mitochondrial β oxidation in HepG2 cells, leading to lipid accumulation [179].…”

Section: Vitamin B Metabolism and Mafldmentioning

confidence: 99%

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

Fu,

Wang,

Qin

2024

Metabolites

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Metabolic-associated fatty liver disease (MAFLD), characterized primarily by hepatic steatosis, has become the most prevalent liver disease worldwide, affecting approximately two-fifths of the global population. The pathogenesis of MAFLD is extremely complex, and to date, there are no approved therapeutic drugs for clinical use. Considerable evidence indicates that various metabolic disorders play a pivotal role in the progression of MAFLD, including lipids, carbohydrates, amino acids, and micronutrients. In recent years, the medicinal properties of natural products have attracted widespread attention, and numerous studies have reported their efficacy in ameliorating metabolic disorders and subsequently alleviating MAFLD. This review aims to summarize the metabolic-associated pathological mechanisms of MAFLD, as well as the natural products that regulate metabolic pathways to alleviate MAFLD.

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Mitochondrial folate metabolism–mediated α-linolenic acid exhaustion masks liver fibrosis resolution

Cited by 7 publications

References 54 publications

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Apollo-NADP ⁺ reveals in vivo adaptation of NADPH/NADP ⁺ metabolism in electrically activated pancreatic β cells

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

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Mitochondrial folate metabolism–mediated α-linolenic acid exhaustion masks liver fibrosis resolution

Cited by 7 publications

References 54 publications

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl4-induced liver fibrosis in mice

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl4-induced liver fibrosis in mice

Apollo-NADP + reveals in vivo adaptation of NADPH/NADP + metabolism in electrically activated pancreatic β cells

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

Contact Info

Product

Resources

About

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Ergothioneine suppresses hepatic stellate cell activation via promoting Foxa3-dependent potentiation of the Hint1/Smad7 cascade and improves CCl₄-induced liver fibrosis in mice

Apollo-NADP ⁺ reveals in vivo adaptation of NADPH/NADP ⁺ metabolism in electrically activated pancreatic β cells