Frontiers in Nutrition
·
2025
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IF 5.1
Ling Zhang,Zhou Peng,Caiyu Lin,Haixia Hu,Juan Du,Siqi Huang,Shan Huang,Jianfang Gao,Xirong Guo
Background: Traditional obesity interventions are often unsuitable for children. Breastfeeding has been shown to reduce obesity risk, potentially through bioactive metabolites in human milk. Here, we identified a human milk-derived metabolite, uridine 5′-monophosphate (5′-UMP), whose role in lipid metabolism and thermogenesis remains largely unknown.Methods: Untargeted metabolomics was performed on colostrum samples from obese and healthy mothers to identify obesity-associated metabolites. Zebrafish larvae and human preadipocytes were used to evaluate the anti-obesity effects of 5′-UMP. Lipid accumulation was assessed by Oil Red O and Nile Red staining, while mitochondrial function was analyzed using transgenic zebrafish [Tg(Xla. Eef1a1: mlsEGFP)] and fluorescent imaging.Results: Pyrimidine metabolism was significantly enriched in obese mothers, with orotate and 5′-UMP levels altered. Targeted analysis confirmed the presence of 5′-UMP in colostrum. Zebrafish toxicity assays confirmed 5′-UMP safety up to 200 μM. In the high-fat diet-induced zebrafish obesity model, 5′-UMP treatment significantly reduced abdominal lipid accumulation. In adipocytes, 5′-UMP enhanced mitochondrial respiration and increased mRNA and protein expression of PGC1-α and UCP1. Furthermore, mitochondrial fluorescence intensity and protein levels of NRF1 and MFN2 were elevated, indicating enhanced mitochondrial biogenesis and activity.Conclusion: Maternal obesity is associated with changes in the human milk metabolome. 5′-UMP, a nucleotide metabolite enriched in human milk, promotes thermogenesis and mitochondrial activation, effectively ameliorating obesity in zebrafish and human adipocytes. These findings support its potential as a safe, milk-derived therapeutic candidate for pediatric obesity intervention.
研究领域:
营养学
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代谢生物学
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分子生物学
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儿科学
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转化医学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Food Bioengineering
·
2024
·Vol. 3
·期 2
·151-159
·
IF 0
Ziye Zhao,Ning Nie,Xinwei Li,Ye Shi,Xudong Liu,Yifei Zhang
Nucleotides, such as uridine 5′-monophosphate (5′-UMP) and cytidine 5′-monophosphate (5′-CMP), are heavily demanded as food additives, dietary supplements, and medicinal intermediates. Although enzymatic phosphorylation is an effective approach to producing these nucleosides, its practical application is challenging due to the need for the expensive enzymes and coenzyme guanosine-5′-triphosphate (GTP). Here we prepared biocompatible calcium-based nanoflowers incorporated with cascade enzymes, uridine-cytidine kinase (UCK) and acetate kinase (ACK), for the production of nucleotides. The spatial distribution of these enzymes was optimized to maximize their catalytic performances. The most active nanoflowers (Ca 3 (PO 4 ) 2 & ACK)& UCK that display the rate-limiting enzyme UCK on the outer layer were used in a packed-bed reactor for continuous synthesis of 5′-UMP and 5′-CMP. The catalytic performance of the catalyst retained over 80% within 10 h, showing good operational stability.
研究领域:
生物催化
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纳米技术
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酶工程
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生物化学
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食品科学
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药物化学
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DOI
SCIENCE OF THE TOTAL ENVIRONMENT
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2022
·
IF 10.753
Yiwei Fang,Zhiliang Chen,Jinyu Chen,Minqi Zhou,Yuanyao Chen,Rong Cao,Chunyan Liu,Kai Zhao,Min Wang,Huiping Zhang
Mono(2-ethylhexyl) phthalate (MEHP) is a metabolite of DEHP which is one of phthalic acid esters (PAEs) widely used in daily necessities. Moreover, MEHP has been proven to have stronger biological toxicity comparing to DEHP. In particular, several recent population-based studies have reported that intrauterine exposure to MEHP results in adverse pregnancy outcomes. To explore the mechanisms and metabolic biomarkers of MEHP exposure, we examined the metabolic status of HTR-8/Svneo cell lines exposed to different doses of MEHP (0, 1.25, 5.0, 20 μM). Global and dose–response metabolomics tools were used to identify metabolic perturbations and sensitive markers associated with MEHP. Only 22 metabolic features (accounted for <1 %) were significantly changed when exposed to 1.25 μM. However, when the exposure dose was increased to 5 or 20 μM, the number of significantly changed metabolic features exceeded 300 (approximately 10 %). In particular, amino acid metabolism, pyrimidine metabolism and glutathione metabolism were widely affected according to the enrich analysis of those significant altered metabolites, which has and have previously been reported to be closely related to fetal development. Moreover, 5′-UMP and N -acetylputrescine with the lowest effective concentrations (EC −10 = 0.1 μM and EC +10 = 0.11 μM, respectively) were identified as sensitive endogenous biomarkers of MEHP exposure.
研究领域:
毒理学
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生殖生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）