Toxics
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2023
·Vol. 11
·期 2
·184
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IF 4.6
Huazhong Zhang,Jinsong Zhang,Jinquan Li,Zhengsheng Mao,Jian Qian,Cheng Zong,Hao Sun,Beilei Yuan
Diquat (DQ), a widely used bipyridyl herbicide, is associated with significantly higher rates of kidney injuries compared to other pesticides. However, the underlying molecular mechanisms are largely unknown. In this study, we identified the molecular changes in the early stage of DQ-induced kidney damage in a mouse model through transcriptomic, proteomic and metabolomic analyses. We identified 869 genes, 351 proteins and 96 metabolites that were differentially expressed in the DQ-treated mice relative to the control mice (p< 0.05), and showed significant enrichment in the PPAR signaling pathway and fatty acid metabolism. Hmgcs2, Cyp4a10, Cyp4a14 and Lpl were identified as the major proteins/genes associated with DQ-induced kidney damage. In addition, eicosapentaenoic acid, linoleic acid, palmitic acid and (R)-3-hydroxybutyric acid were the major metabolites related to DQ-induced kidney injury. Overall, the multi-omics analysis showed that DQ-induced kidney damage is associated with dysregulation of the PPAR signaling pathway, and an aberrant increase in Hmgcs2 expression and 3-hydroxybutyric acid levels. Our findings provide new insights into the molecular basis of DQ-induced early kidney damage.Keywords:diquat;kidney injury;multi-omics;fatty acid metabolism;PPAR signaling pathway
研究领域:
毒理学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Current Computer-Aided Drug Design
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2024
·
IF 1.5
Lingxiao Zhang,Chenghao Yang,Xinyue Ding,Hui Zhang,Yuling Luan,Yueer Tang,Zongjun Liu
Background: Berberine (BBR), also known as berberine hydrochloride, was isolated from the rhizomes of the Coptis chinensis. Studies have reported that BBR plays an important role in glycolipid metabolism, including insulin (IR). The targets, and molecular mechanisms of BBR against hyperlipid-induced IR is worthy to be further studied. Material and methods: The related targets of BBR were identified via Pharmmapper database and relevant targets of diabetes were obtained through GeneCards and Online Mendelian Inheritance in Man (OMIM) database. The common targets were employed with the STRING database and visualized with the protein-protein interactions (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to explore the biological progress and pathways. In vitro, human hepatocellular carcinomas (HepG2) cell was used as experimental cell line, and an insulin resistant HepG2 cell model (IR-HepG2) was constructed using free fatty acid induction. After intervention with BBR, glucose consumption and uptake in HepG2 cells were observed. Molecular docking was used to test the interaction between BBR and key targets, and real-time fluorescence quantitative PCR was used to detect the regulatory effect of BBR on related targets. Results: 262 overlapped targets were extracted from BBR and diabetes. In the KEGG enrichment analysis, the peroxisome proliferator activated receptor (PPAR) signaling pathway was included. In vitro experiments, BBR can significantly increase sugar consumption and uptake in IR HepG2 cells, while PPAR inhibitors can weaken the effect of BBR on IR-HepG2. Conclusion: The PPAR signaling pathway is one of the important pathways for BBR to improve high-fat-induced insulin resistance in HepG2 cells.
研究领域:
药理学
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分子生物学
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内分泌学
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转化医学
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代谢疾病研究
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
·Vol. 67
·期 22
·2300258
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IF 5.2
Yiju Li,Zhi Feng,Tianliang Wu,Haixi You,Wei Wang,Xuebo Liu,Long Ding
Scope The obesity epidemic continues to be a major global public health threat with limited effective treatments. Peptides are a group of promising bioactive molecules. Both in vivo and in vitro studies have demonstrated that quinoa has potential prebiotic benefits. Thus, the present study aims to investigate the influence of quinoa peptides (QP) consumption on obesity and its underlying mechanisms in high-fat diet (HFD)-induced mice. Methods and results QP (1000 mg kg −1 day −1 ) is administered to HFD mice for 8 weeks, and is found to significantly reduce the body weight, and plasma levels of triacylglycerol (TG) and total cholesterol (TC) compare to the HFD group. In addition, QP significantly decreases lipid accumulation in the liver caused by HFD. The liver transcriptome analysis shows that the alleviation of QP on obesity is related to the PPAR signaling pathway. QP upregulates the expressions of PPAR-α and its related genes and downregulates the expressions of PPAR-γ and its downstream genes. Furthermore, QP remodels the community composition of gut microbiota by lowering the ratio of Firmicutes c Bacteroidetes (F/B). Conclusion These findings suggest that QP consumption alleviates HFD-induced obesity by regulating the PPAR-α/γ signaling pathway in the liver and community structure of gut microbiota.
研究领域:
营养学
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分子生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2021
·Vol. 45
·期 11
·e13976
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IF 2.72
Longkai Shi,Emad Karrar,Xingguo Wang
Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatopathy caused by disordered lipid metabolism in the liver. Sesamol, a phenolic compound derived from sesame oil, has been shown to inhibit obesity, hyperlipidemia, and atherosclerosis in previous investigations. However, the preventive effect of sesamol against hepatic steatosis and oxidative stress in NAFLD has not been well-studied. In this work, sesamol was observed to alleviate lipid accumulation and oxidative stress in high oleic acid (300 μM)/cholesterol (25 μM) induced HepG2 cells, thus indicating that sesamol was involved in regulating hepatic lipid metabolism and oxidative injury. Mechanism studies found that the activated peroxisome proliferator-activated receptors (PPAR) signaling pathway by sesamol intervention up-regulated gene and protein expressions related to fatty acid oxidation and cholesterol efflux and catabolism, thus accelerating lipid consumption and reducing intracellular lipid accumulation in the process of NAFLD. These data suggested that sesamol can effectively ameliorate hepatic steatosis and sesamol riched sesamol oil may be a potential agent for finding therapeutic strategies to treat the NAFLD. Practical applications Sesamol and sesamol-rich sesame oil have received much attention due to their performance on hepatic lipid regulation. The results of this study indicate that sesamol treatment could ameliorate hepatic steatosis by inhibiting lipid accumulation and oxidative stress, thus demonstrating that sesamol and sesame oil can be used for functional foods and nutraceutical applications in the future. In addition, the present work provides knowledge of the effects of sesamol on NAFLD and involved mechanisms, and further supplies nutritional guidelines for sesame oil consumption.
研究领域:
营养学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2025
·
IF 5.9
Li Xin,Ma Yuntian,Wang Xin,Lü Xin
Macronutrients participate in vital biological processes and are critical in regulating organismal health. DL-norvaline, a nonproteinogenic amino acid, is an important pharmaceutical intermediate and a functional food ingredient for obesity control. This study aimed to explore the ameliorative effect and underlying mechanisms of DL-norvaline on lipid metabolism in high-fat diet-induced obese mice. The results showed that DL-norvaline inhibited adipogenesis and lipid accumulation in 3T3-L1 adipocytes, ameliorated tissue weight, food efficiency ratio and serum biochemical markers in obese mice. The combined transcriptomics and lipidomics analysis showed that lipid metabolism of adipose tissue such as sphingolipid and glycerophospholipid metabolism was ameliorated in obese mice after DL-norvaline treatment, particularly ceramides, via regulating peroxisome proliferators-activated receptor signaling pathway. This study offered a complementary perspective for exploring the effects of amino acids on lipid metabolism and speculated the possible mechanisms of ameliorating lipid-metabolism disorders by DL-norvaline in obese mice.
研究领域:
生物化学
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分子生物学
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营养学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Nutrients
·
2025
·Vol. 17
·期 10
·1693
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IF 5
Binsong Han,Yuhui Ye,Cunzheng Zhang,Lina Zhang,Peng Zhou
Background: Camel milk is considered to be an important source of bioactive peptides with potential anti-diabetic effects. However, the mechanism by which these active peptides exert their anti-diabetic effects is not clear. The aim of this study was to systematically evaluate the in vivo anti-diabetic effects of Leucine-Leucine-Proline-Lysine (LLPK), a novel dipeptidyl peptidase-4 (DPP-4) inhibitory peptide identified from the in vitro gastrointestinal digestion product of camel milk.Methods: Adb/dbdiabetic mouse model was used, and LLPK was administered to mice at doses of 50 mg/kg BW and 100 mg/kg BW as a daily oral gavage for 30 days. The effects of LLPK on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum lipid levels were monitored, and possible mechanisms of action were elucidated using proteomics.Results: The results demonstrated that LLPK significantly improved diabetic symptoms, including FBG, OGTT, ITT, and serum lipid levels indb/dbdiabetic mice. Furthermore, significantly increased levels of serum glucagon-like peptide 1 (GLP-1) and reduced serum DPP-4 activity were observed in the LLPK-treated group compared to the control group. Hepatic proteomics indicated that LLPK improved glucose and lipid metabolism via the PPAR signaling pathway, where the key targets were Scd1, Acox1, Acaa1b, Slc27a1, Acsl1, and Ehhadh.Conclusions: In summary, this study provided new insights into the anti-diabetic mechanisms of camel milk and supported the development of camel milk-based anti-diabetic functional foods or nutraceuticals.
研究领域:
营养学
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分子生物学
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代谢研究
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
·
IF 3.1
Xiang Li,Kevin Shyong Wei Tan,Li Wang
This study was aimed to explore the alleviating effect of black rice (BR), black peeled rice (BPR), and black rice bran (BRB) on lipid metabolism disorders in hyperlipidemia mice caused by high fat and cholesterol diet (HFCD). Combined untargeted metabolomics and RNA-seq transcriptomics analysis was used to demonstrate the potential mechanism regulated by BR, BPR and BRB. The untargeted metabolomics analysis indicated that BR especially BRB significantly increased Deoxycholic acid, 5-Dehydroavenasterol, scyllo-Inositol, Phloretin, 5-KETE, Lipoxin B4, 3,4-Dihydroxybenzeneacetic acid levels, while BRB significantly regulated PPAR signaling pathway, Arachidonic acid metabolism, Regulation of lipolysis in adipocytes, Steroid biosynthesis, and Sphingolipid signaling pathway, which closely linked to lipid metabolism. Furthermore, RNA-seq transcriptomics analysis showed that BRB obviously regulated Steroid hormone biosynthesis ( Cyp2b9 , Cyp2b13 and Cyp2c38 ) and PPAR signaling pathway ( Pparg , Fabp4 , Cd36 and Plin4 ), which were closely associated with inflammation and lipid metabolism. Moreover, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis validated this. The obtaining results were hoping to reveal the detailed mechanism of BRB in alleviating hyperlipidemia and provide some insights for developing a new kind of natural anti-hyperlipidemia drug.
研究领域:
营养学
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Bing Zheng,Tianxiang Ao,Xiaole Zhao,Yi Chen,Jianhua Xie,Xingcai Gao,Li Liu,Xiaobo Hu,Qiang Yu
The impact of different forms of dietary fiber (total, insoluble or soluble) derived from the same source on health remains incompletely understood. In this study, the effects of total, insoluble, and soluble dietary fiber extracted from highland barley (HDF, HIDF, and HSDF) on combating obesity were evaluated and compared. A high-fat diet (HFD) was used to induce obesity in a murine model, followed by gavage administration of HDF, HIDF, or HSDF, and a comprehensive multi-omics approach was utilized to assess and compare the effects of these dietary fibers on obesity-related parameters. The results showed that all three dietary fibers significantly reduced body weight, modified blood lipid profiles, and ameliorated tissue damage in HFD-fed mice. Additionally, 16S rRNA sequencing analysis of mice feces showed that three types of dietary fiber exerted varying degrees of impact on the composition and abundance of gut microbiota while simultaneously promoting the biosynthesis of short-chain fatty acids. Specifically, HDF supplementation remarkably enhanced the abundance of Coprococcus , while HIDF and HSDF supplementation elevated the levels of Akkermansia and Allobaculum , respectively. Transcriptomic and proteomic results suggested the PPAR signaling pathway as a central regulatory mechanism influenced by these fibers. HDF and HIDF were particularly effective in modulating biological processes related to triglyceride and fatty acid metabolism, identifying Abcc3 and Dapk1 as potential targets. Conversely, HSDF primarily affected processes related to membrane lipids, ceramides, and phospholipids metabolism, with Pck1 identified as a potential target. Collectively, HDF, HIDF, and HSDF demonstrated distinct mechanisms in exerting exceptional anti-obesity properties. These insights may inform the development of personalized dietary interventions for obesity.
研究领域:
营养学
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分子生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Future Foods
·
2025
·
IF 7.2
Haohao Tang,Luyi Wang,Wanqiang Sun,Guocheng Du,Jingwen Zhou,Jian Chen,Xin Guan
Cultured meat provides a sustainable and safe alternative to traditional meat production by culturing animal cells in vitro . Cultured fat is an important component of cultured meat, contributing to its flavor, texture, and nutrition. Induced adipogenic differentiation is the most important step in the production of cultured fat, but conventional adipogenic inducer cocktails are complex and contain non-food-grade substances, which introduces a food safety risk for cultured meat products. Here we demonstrated that a food-grade substance, peanut oil (P-OIL), promoted adipogenic differentiation and lipid accumulation of bovine adipose-derived stem cells (bADSCs), based on which a simple and efficient approach was developed to produce cultured bovine fat. Mechanistic analysis showed that P-OIL upregulated genes involved in lipid synthesis and storage, such as PPARγ, CPT2 , and LPL , by activating the PPAR signaling pathway during adipogenesis. Notably, the lipid composition of cultured bovine fats generated using P-OIL induction was similar to that of fats obtained from farmed cattle, but free of trans -fatty acids. This study provides valuable insights into the production of safe, healthy, and nutritious cultured fats.
研究领域:
生物工程
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食品科学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Environmental Chemical Engineering
·
2023
·
IF 7.7
Fei Shi,Minshan Yao,Yao Huang,Zhilong Chen,Jin Xiao,Fanbin Zhan,Yanan Li,Li Lin,Zhendong Qin
Antibiotics are used to treat illnesses in animals and humans worldwide. Yet, many antibiotics and other secondary metabolites can contaminate the water supply, creating a substantial risk to human health. A comprehensive investigation is currently focusing on the systematic effects of dietary antibiotics on fish liver, particularly on their impacts on oxidative stress , transcriptome profiles, toxicity, and apoptosis. In the present study, healthy grass carp were treated orally with 10 mg/kg enrofloxacin or florfenicol for 14 days. The enzyme activity outcomes reflected that the administration of enrofloxacin or florfenicol could significantly induce oxidative stress by decreasing CAT , SOD and GPx and increasing MDA. In addition, KEGG analysis showed that both antibiotics activated the PPAR signal pathway. The expression levels of the six genes, namely FABP6, APOA1, CYP27A1, ACSL1, CPT1A , and ANGPTL4, in the PPAR signal pathway were determined to further clarify the transcriptomic data. Enrofloxacin induced apoptosis in grass carp liver tissue, while hepatocytes from grass carp treated with enrofloxacin and florfenicol activated cytotoxicity and apoptosis. The present study suggests that antibiotics can induce antioxidant stress, impair the immune system, and attenuate the PPAR signal pathway in the grass carp liver, thus being harmful to grass carp as a dietary supplement, mainly within the aquaculture industry .
研究领域:
水产养殖
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毒理学
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分子生物学
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Yue Zhang,Hui Zhao,Qianxi Feng,Rui Guo,Li Zhong,Shengxian Liang
Benzotriazole ultraviolet stabilizers (BUVSs) are pervasive environmental contaminants that pose significant risks to human health. This study evaluated the effects of three typical BUVSs (UV-328, UV-329, and UV-P) on human mesenchymal stem cells (hMSCs), which play crucial roles in tissue maintenance and repair. hMSCs were exposed to BUVSs across a range of concentrations, and their maintenance and differentiation capacities were assessed. At concentrations below 50 μM, no significant cytotoxicity was observed. However, at non-cytotoxic doses, UV-P exhibited stronger effects on the differentiation of hMSCs compared to UV-328 and UV-329, significantly inhibiting adipogenesis and enhancing osteogenesis. Mechanistically, UV-P was found to significantly enrich the PPAR signaling pathway during both differentiation processes. Dual-luciferase reporter assays confirmed UV-P's interaction with PPARγ_LBD at an alternate binding site outside the canonical pocket. These findings raise concerns about the health impacts of BUVSs, particularly UV-P, and underscore the need for further investigation into their toxicological profiles.
研究领域:
细胞生物学
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毒理学
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环境健康科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Xun’e Yi,Haiyu Qin,Guangyu Li,Ren Kong,Chunsheng Liu
Tricresyl phosphate (TCP) has received extensive attentions due to its potential adverse effects, while the toxicological information of TCP isomers is limited. In this study, 2 h post-fertilization zebrafish embryos were exposed to tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) or tri-p-cresyl phosphate (TpCP) at concentrations of 0, 100, 300 and 600 μg/L until 120 hpf, and the cardiotoxicity and mechanism of TCP isomers in zebrafish embryos/larvae were evaluated. The results showed that ToCP or TmCP exposure induced cardiac morphological defects and dysfunction in zebrafish, characterized by increased distance between sinus venosus and bulbus arteriosis, increased atrium and pericardial sac area, trabecular defects, and decreased heart rate and blood flow velocity, while no adverse effects of TpCP on zebrafish heart were found. Transcriptomic results revealed that extracellular matrix (ECM) and motor proteins, as well as PPAR signaling pathways, were included in the cardiac morphological defects and dysfunction induced by ToCP and TmCP. Co-exposure test with D-mannitol indicated that the inhibition of energy metabolism by ToCP and TmCP affected cardiac morphology and function by decreasing osmoregulation. This study is the first to report the cardiotoxicity induced by TCP in zebrafish from an isomer perspective, providing a new insight into the toxicity of TCP isomers and highlighting the importance of evaluating the toxicity of different isomers.
研究领域:
环境毒理学
·
发育生物学
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分子生物学
✓ 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）