Regulation of Ferroptosis in Obesity: Muscle Type-Specific Effects of Dietary Restriction and Exercise DOI Creative Commons

Fujue Ji,

Haesung Lee,

Jong Hee Kim

et al.

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

Published: Aug. 7, 2024

Background Obesity is a significant global health issue and risk factor for numerous diseases. Ferroptosis, an iron-dependent regulated cell death, triggered by iron overload the excessive accumulation of lipid peroxidation mediated reactive oxygen species. Studies has identified strong association between ferroptosis obesity. Additionally, dietary restriction (DR) DR combined with exercise (DR+Ex) are effective strategies managing obesity ferroptosis. However, regulation its signaling pathways in skeletal muscle under conditions obesity, DR, DR+Ex remains poorly understood. Methods Mice were divided into four groups: normal diet, high-fat DR+Ex. All mice fed ad libitum either or diet first 14 weeks, followed respective interventions subsequent 8 weeks. examined immunohistochemistry, Hematoxylin & Eosin, Masson’s trichrome, Prussian blue staining, Western-Immunoblot. Results The resulted increased inflammatory infiltration, fibrosis, accumulation. Red white showed expression 4-HNE, GPX4 NCAO4, respectively. reduced downstream 4-HNE regulating red muscle. Conclusion Due to metabolic differences, obesity-induced exhibiting fiber type-specificity. Specifically, respond through different pathways; can inhibit GPX4. This deepens understanding mechanisms related death provides scientific data support personalized treatment

Language: Английский

Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis DOI Creative Commons
Jiahui Ni, Lijie Zhang, Guize Feng

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107128 - 107128

Published: March 2, 2024

The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced by restoring intestinal homeostasis via inhibition ferroptosis. By CETSA assay DARTS assay, identified carbonic anhydrase IX (CAIX, CA9) as direct target VA. binding VA to CA9 causes insulin-induced gene-2 (INSIG2) interact stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading translocation SCAP-SREBP1 from endoplasmic reticulum (ER) Golgi apparatus for cleavage into mature SREBP1. activation SREBP1 induced then significantly facilitated transcription SCD1 exert an inhibitory effect inhibiting excessive death cells caused ferroptosis, effectively preserved integrity barrier prevented progression unresolved inflammation. In conclusion, our study demonstrated could alleviate through CA9/STIM1-mediated providing promising candidate UC.

Language: Английский

Citations

16
Lizhong decoction ameliorates ulcerative colitis by inhibiting ferroptosis of enterocytes via the Nrf2/SLC7A11/GPX4 pathway DOI
Wen Li, Yu Wang, Yun Zhang

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 326, P. 117966 - 117966

Published: Feb. 22, 2024

Language: Английский

Citations

15
Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update DOI Open Access

Júlia Pauli De Cól,

Enzo Pereira de Lima,

Fernanda Moris Pompeu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3694 - 3694

Published: March 26, 2024

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, syndrome are frequently present; these conditions related to lipogenesis systemic inflammation. This study aimed review connection between MAFLD. The inflammatory process, cellular alterations hepatocytes stellate cells, hypercaloric diet, sedentarism aggravate prognosis of patients with Thus, understand modulation physiopathology it is necessary include organokines involved this process (adipokines, myokines, osteokines, hepatokines) their clinical relevance project future perspectives condition bring light new possibilities therapeutic approaches. Adipokines responsible for activation distinct signaling different tissues, such as insulin pro-inflammatory cytokines, which important balancing substances avoid MAFLD its progression. Myokines improve quantity quality adipose contributing avoiding development Finally, hepatokines decisive improving or not progression through regulation anti-inflammatory organokines.

Language: Английский

Citations

13
Ferroptosis: Biology and Role in Gastrointestinal Disease DOI
Juan-José Escuder‐Rodríguez, Deguang Liang, Xuejun Jiang

et al.

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(2), P. 231 - 249

Published: March 1, 2024

Language: Английский

Citations

12
Immune Dysregulation in Endometriomas: Implications for Inflammation DOI Open Access
Izabela Dymanowska-Dyjak,

Barbara Terpiłowska,

Izabela Morawska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4802 - 4802

Published: April 28, 2024

The most common manifestation of endometriosis, a condition characterized by the presence endometrial-like tissue outside uterus, is endometrioma, cystic ovarian lesion. It commonly occurring associated with chronic pelvic pain exacerbated prior to and during menstruation, as well infertility. exact pathomechanisms endometrioma are still not fully understood. Emerging evidence suggests pivotal role immune dysregulation in pathogenesis endometriomas, primarily influencing both local systemic inflammatory processes. Among factors implicated creation milieu alterations serum levels several cytokines stand out, including IL-6, IL-8, IL-1β, along abnormalities innate system. While numerous signaling pathways have been suggested play process linked only NF-κB has conclusively demonstrated be involved. Additionally, increased oxidative stress, resulting from contributing identified primary driver inflammation condition. This article reviews current understanding dysfunctions their implications for inflammation.

Language: Английский

Citations

11
A guide to ferroptosis in cancer DOI Creative Commons
Fatma Isil Yapici, Christina M. Bebber, Silvia von Karstedt

et al.

Molecular Oncology, Journal Year: 2024, Volume and Issue: 18(6), P. 1378 - 1396

Published: April 8, 2024

Ferroptosis is a newly identified iron‐dependent type of regulated cell death that can also be regarded as caused by the specific collapse lipid antioxidant defence machinery. has gained increasing attention potential therapeutic strategy for therapy‐resistant cancer types. However, many ferroptosis‐inducing small molecules do not reach pharmacokinetic requirements their effective clinical use yet. Nevertheless, optimization under development. In this review, we summarize current understanding molecular pathways regulating ferroptosis, how cells protect themselves from induction ferroptotic death, and better metabolism represent vulnerabilities ferroptosis‐based therapies. Lastly, discuss context‐dependent effect ferroptosis on various types within tumor microenvironment address controversies tissue might impact systemic immunity in paracrine manner.

Language: Английский

Citations

9
Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota DOI Open Access
Jinzhi Wang, Yuanyuan Yao, Ting Yao

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2343 - 2343

Published: July 19, 2024

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role mechanism HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover beneficial effects its detailed UC. Experimental was induced by 2.5% dextran sodium sulfate (DSS) for seven days. ameliorated DSS-induced mice, showing marked improvement weight loss, colon length, colonic pathological severity, levels TNFα IL6 serum. A combination informatics, network pharmacology, molecular docking identified eight key targets multi-pathways influenced As highlight, experimental validation demonstrated that PTGS2, marker ferroptosis, along other indicators ferroptosis (such as ACSL4, Gpx4, lipid peroxidation), were regulated vivo vitro. Additionally, supplement increased diversity gut microbiota, decreased relative abundance Proteobacteria Gammaproteobacteria, restored bacteria (Lachnospiraceae_NK4A136_group Prevotellaceae_UCG-001). In conclusion, an effective nutritional against suppressing modulating microbiota.

Language: Английский

Citations

9
Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome DOI Creative Commons
Arturs Zemitis, Juris Vanags, Theresa Schiemer

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 23, 2025

Purpose PEXS was first described in 1917, yet its etiology still needs clarification. An imbalance between oxidants and antioxidants plays a significant role. leads to various ocular complications, including increased risk during cataract surgery due weak zonules, lens dislocation, reduced visual outcomes. Our study investigates whether metabolomics can provide insights into this pathology. Methods The included 183 patients undergoing at Pauls Stradins Clinical University Hospital. 104 did not have PEXS, while 79 were diagnosed with the condition. Intraocular fluid samples from these analyzed using targeted metabolite analysis, performed through HILIC liquid chromatography coupled mass spectrometry detection. Results aqueous humor of contains statistically higher levels cystine ( p < 0.001), citrulline phenylalanine = 0.041), tyrosine 0.025), serine 0.030), arginine 0.017), lactic acid 0.055), tryptophan creatinine 0.022). These results suggest potential link ferroptosis. Conclusion Ferroptosis is form programmed cell death characterized by iron-dependent LPO. inhibition antiporter system X c − oxidative stress, suggesting that changes seen could be linked findings indicate cysteine synthesis occurs via transsulfation pathway, attributable inhibiting . Treatment pseudoexfoliation should lower stress inside anterior chamber reducing uptake PUFAs, iron levels, supplementation.

Language: Английский

Citations

1
Sodium butyrate alleviates DSS-induced inflammatory bowel disease by inhibiting ferroptosis and modulating ERK/STAT3 signaling and intestinal flora DOI Creative Commons

Yingyin Liu,

Nan Chen, Han He

et al.

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: March 3, 2025

Background Inflammatory bowel disease (IBD), encompassing Crohn's (CD) and ulcerative colitis (UC), can seriously impact patients' quality of life. Sodium butyrate (NaB), a product dietary fiber fermentation, has been shown to alleviate IBD symptoms. Some studies have that it is related ferroptosis. However, the precise mechanism linking NaB, IBD, ferroptosis not clear.

Language: Английский

Citations

1
Vitamin E and GPX4 cooperatively protect treg cells from ferroptosis and alleviate intestinal inflammatory damage in necrotizing enterocolitis DOI Creative Commons

Shunchang Luo,

Yingying Zeng,

Baozhu Chen

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103303 - 103303

Published: Aug. 8, 2024

The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues,contribute to excessive inflammation and necrosis, yet precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from disrupted lipid redox metabolism, is focus this investigation. Specifically, study delves into ferroptosis Treg cells context NEC observes protective effects exerted by vitamin E intervention, which aims mitigate cells. To investigate reduction intestine, we analyzed its association with multiple angles. We constructed mouse specific knockout Gpx4 cells, aiming examine impact on injury localized inflammation. Ultimately, employed treatment intestine's monitoring subsequent amelioration inflammatory damage. diminution attributed diminished GPX4 expression. Gpx4-deficient exhibit impaired immunosuppressive function are susceptible ferroptosis. This exacerbates damage response NEC. Notably, Vitamin can inhibit subsequently alleviating Additionally, bolsters anti-lipid peroxidation capability upregulating expression GPX4. In NEC, represents significant factor contributing tissue an exaggerated response. pivotal for viability functionality exhibits thereby enhancing their function, plays crucial role mitigating

Language: Английский

Citations

8