Biomolecules
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2025
·Vol. 15
·期 4
·492
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IF 4.8
Xia Xu,Chunguang Cui,Xin Du,Jine Chen,Xiuling He,Linbao Zhu,Chengjie Hu,Fang Xu,Chenkai Ma,Shaofang Yu,Xingjian He,Houhui Song,Yongqiang Wang
Lipid metabolism serves as the primary energy source for organisms. Silkworm eggs for spring use are divided into two types: autumn-produced eggs for next spring rearing (AS) and spring-produced eggs for next spring rearing (SS). Production practice revealed significant differences in hatching rates between these two types of silkworm production strain QiufengA. In this study, we identified differentially expressed genes (DEGs) primarily enriched in energy metabolism pathways. In particular, the PPARs are involved in energy regulation through lipid metabolism. Furthermore, both AS and SS contained the same eight long-chain fatty acids but in different amounts. Interference with PPARs activity in silkworm eggs disrupted the expression of key genes in this pathway, resulting in a significant decrease in hatching rate. Additionally, knockdown of the pathway key geneBmPlin4led to the reduction in lipid droplets. In conclusion, PPARs regulates the hatching rate of silkworms mainly by affecting lipid metabolism. This study proved the importance of PPARs for hatching and identifies them as potential target genes for population control.
研究领域:
昆虫学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 3
·1674-1684
·
IF 6.1
Jingqi Zhao,Yantong Sun,Cuiping Yuan,Tiezhu Li,Yuan Liang,Haoyang Zou,Jie Zhang,Li Ren
As a natural pigment in food, quercetin possesses multiple biological activities and plays a crucial role in regulating metabolic syndrome. Herein, we aim to explore the potential mechanism of quercetin to ameliorate hepatic fat accumulation. In vivo experiments showed that quercetin significantly relieved inflammation response by decreasing the serum TNF-α and IL-6 levels and also improved high-fat diet-induced hepatic steatosis without other organ injuries. Quercetin can effectively reduce lipid aggregation and down-regulate the protein expression of PCK1 in HepG2 cells induced by oleic acid and palmitic acid, indicating that inhibiting gluconeogenesis leads to hepatic fat accumulation reduction. Furthermore, molecular docking results suggested that quercetin can bind to both PPARα and PPARγ, with an even more potent binding affinity than indeglitazar, a pan-agonist of PPARs. In conclusion, quercetin may regulate gluconeogenesis to ameliorate hepatic fat accumulation via targeting PPARα/γ.
研究领域:
药理学
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代谢学
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营养学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Meiqi Wang,Beixuan Yang,Xin Li,Huanhuan Ma,Xia Ou,Zeren Dawa,Fangle Liu,Chenchen Zhu,Chaozhan Lin
Background Nonalcoholic fatty liver disease (NAFLD), which is characterized by the accumulation of fat in the liver, has emerged as a leading cause of chronic liver diseases and malignancies. However, there remains a scarcity of approved therapeutic interventions. Brunodelphinine A (BruA) is a diterpenoid alkaloid isolated from Delphinium brunonianum Royle. in our previous study. It was evaluated with strong activity of lipid-lowering. Nevertheless, its precise effects and mechanisms in the treatment of NAFLD remain unexplored. Purpose The present study aims to elucidate the effects of BruA against NAFLD and to investigate its potential pharmacological mechanism. Methods The lipid-lowering and anti-NAFLD effects of BruA were evaluated in the free fatty acid (FFA)-induced cell model and high-fat diet (HFD)-induced mice. Network pharology analysis combined with Non-targeted metabolomics study was used to explore the key mechanism of BruA. Furthermore, molecular docking and cellular thermal shift assay (CETSA) were used to simulate and verify the targeting activation of BruA on the NADPH oxidase 4 (NOX4). The core role of NOX4 in BruA in regulating nicotinamide adenine dinucleotide (NAD + )/Sirtuin 1 (SIRT1) and peroxisome proliferators-activated receptors (PPARs) signaling pathway to improve oxidative stress and lipid metabolic disorders was further focused, and such mechanism was evaluated in WT and NOX4 knockout mice or HepG2 cells. Results BruA dose-dependently reduced FFA-induced lipid accumulation and cell damage in vitro , and mitigated HFD-induced NAFLD in mice. At the metabolite level, BruA improved metabolic disorder in NAFLD mice focusing on the metabolism of arachidonic acid and linolenic acid, which has been considered as signs of oxidative stress, that positively correlated with NAFLD. BruA targeting inhibited NOX4 to mitigate reactive oxygen species (ROS)-mediated oxidative stress and prevent abnormal redox levels, thereby regulating NAD + /SIRT1 in protecting the liver from oxidative damage, and further affected downstream PPARs-related lipid metabolism regulation processes, thus alleviating hepatic lipid accumulation. Furthermore, NOX4 deficiency suppressed the protective effect of BruA in vitro and in vivo . Conclusion BruA improved oxidative stress and lipid metabolic disorders of NAFLD by regulating the NOX4-SIRT1-PPARs signaling axis in vivo and in vitro , and this regulation is targeting dependent on NOX4. For its mechanisms of antioxidant stress and lipid-lowering, there is great therapeutic potential for BruA in the treatment of period with elevated lipids and inflammation production in NAFLD.
研究领域:
药理学
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生物化学
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分子生物学
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药物化学
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细胞生物学
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代谢组学
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药物研发
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肝病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
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IF 5.6
Liu Guanjie,Chang Ling,Qian Yihan,Lin Jiacheng,Shang Zhi,Xu Min,Wang Fang,Sun Xuehua,Jiang Yun,Gao Yueqiu,Kong Xiaoni
Non-alcoholic fatty liver disease (NAFLD) is a predominant contributor to end-stage liver disease in the forthcoming decades. Polygonum perfoliatum L. (PPL) is an herbal medicine with anti-lipid peroxidation and anti-inflammatory properties. However, detailed hepatoprotective effects of PPL against NAFLD and its underlying mechanisms are not fully understood. Here, we found that PPL protects against high fat diet (HFD)-induced hepatic steatosis, lipid peroxidation, and glucose-lipid metabolism dysfunction in NAFLD mice. We therefore performed a label-free quantitative proteomic profiling analysis to determine the effect of PPL treatment on liver tissue proteomics and identified that activated PPARs/CPT1A/CPT2-mediated hepatic fatty acid β-oxidation (FAO) process was significantly altered. In vitro treatment of hepatocytes with PPL confirmed this altered process and FAO inhibitor etomoxir (ETO) attenuated the lipid-lowering activity of PPL in hepatocytes. Ultra-high-performance liquid chromatography/Q Exactive-HFX (UPLC/QE-HFX) was used to determine the material basis of anti-NAFLD activity of PPL. Our results have demonstrated the efficacy and potential mechanisms of PPL as an effective pharmacological therapy of NAFLD.
研究领域:
药理学
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肝病学
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蛋白质组学
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代谢学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
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2025
·
IF 3
Shu-Mei Pan,Wen-Cai Liu,Chun-Yu Xing,Xin-Yue Pu,Qian-Qian Wang,Xuan Zhao,Qi-Chen Zhang,Dan-Dan Wang,Ya-di Zhu
Uridine-5′-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) is a key enzyme in the regulation of bilirubin metabolism and detoxification of a variety of internal and external substances, and its insufficient function can lead to hyperbilirubinemia and affect the metabolic clearance of drugs, food additives, and environmental toxicants. However, there is a lack of safe and effective UGT1A1 inducers in the clinic. This study presents Corylin, an efficient UGT1A1 inducer identified from a series of natural flavonoids and isoflavonoids. Notably, Corylin demonstrated potent induction of intracellular UGT1A1. Furthermore, nuclear receptor reporter gene assays revealed that Corylin dose-dependently activated PPARs and AhR nuclear receptors, with the most robust activation observed in the PPARβ/δ subtype. Animal experiments indicated that Corylin exhibited favorable safety profiles and significant hepatoprotective effects in mice with APAP-induced liver injury, accompanied by marked UGT1A1 expression. Collectively, this study suggests that Corylin is a potential UGT1A1 inducer and a promising candidate for the intervention of liver-related disorders.
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PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Jinlu Han,Jiong Chen,Hong Hu,Yun Song,Mengyan Chen,De Zhao,Wen Shan,Qinghui Zhang,Ling Xu
Background Non-alcoholic fatty liver disease (NAFLD) and its fibrotic progression represent major global health concerns with limited pharmacological interventions. Moronic acid (MA), a natural pentacyclic triterpenoid, has demonstrated anti-inflammatory and metabolic activity, but its role in NAFLD and fibrosis remains unclear. Purpose This study aimed to elucidate the therapeutic potential and mechanism of MA in ameliorating NAFLD and liver fibrosis. Methods The therapeutic effects of MA were evaluated in C57BL/6J mouse models of NAFLD and fibrosis. An integrated multi-omics approach, combining network pharmacology, proteomics, and lipidomics, was used to investigate the underlying mechanism. Direct binding to the identified target, peroxisome proliferator-activated receptors (PPARs), and cellular engagement were confirmed by microscale thermophoresis (MST) and Cellular Thermal Shift Assay (CETSA). The dependency on this pathway was genetically validated using siRNA-mediated gene silencing and further confirmed in a 3D human liver organoid model. Results MA alleviated hepatic steatosis, fibrosis, and metabolic dysregulation in both models. MA activated PPARα/β/γ, as evidenced by molecular docking, dynamics simulations, and increased hepatic expression. In hepatocytes and hepatic stellate cells, MA reduced lipid accumulation and fibrogenesis, effects reversed by PPAR inhibition. Lipidomic profiling showed that MA upregulated glycerophospholipids and sphingolipids and downregulated glycerolipids, consistent with PPAR-driven lipid remodeling. Conclusion MA exerts therapeutic effects against NAFLD and fibrosis through PPAR activation and lipidomic reprogramming. These findings support the potential of MA as a novel phytotherapeutic agent for metabolic liver disease.
研究领域:
药理学
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代谢组学
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肝脏病学
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分子生物学
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天然产物研究
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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
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
·
IF 6.8
Weiqiang Sun,Xuemin Zhang,Ying Qiao,Nathan Griffin,Hongxia Zhang,Li Wang,Hui Liu
Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC 50 (PFOA 100 μM, Gen-X 200 μM, HFPO-TA 30 μM). At the same LC 50 toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2019
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IF 7.65
Zhuo Li,Zhenyang Yu,Changzheng Cui,Fangting Ai,Daqiang Yin
Increasing concerns are earned on the multigenerational hazards of antibiotics due to the connection between their mother-children transfer via cord blood and breast milk and obesity in the children. Currently, Caenorhabditis elegans was exposed to sulfamethoxazole (SMX) over 11 generations (F0–F10). Indicators of obesogenic effects and gene expressions were measured in each generation and also in T11 to T13 that were the offspring of F10. Biochemical analysis results showed that SMX stimulated fatty acids in most generations including T13. The stimulation was resulted from the balance between enzymes for fatty acid synthesis (e.g., fatty acid synthetase) and those for its consumption (e.g., fatty acid transport protein). Gene expression analysis demonstrated that the obesogenic effects of SMX involved peroxisome proliferator activated receptors (PPARs, e.g., nhr-49 ) and insulin/insulin-like signaling (IIS) pathways (e.g., ins-1 , daf-2 and daf-16 ). Further epigenetic analysis demonstrated that SMX caused 3-fold more H3K4me3 binding genes than the control in F10 and T13. In F10, the most significantly activated genes were in metabolic and biosynthetic processes of various lipids, nervous system and development. The different gene expressions in T13 from those in F10 involved development, growth, reproduction and responses to chemicals in addition to metabolic processes.
研究领域:
药理学
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毒理学
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表观遗传学
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分子生物学
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发育生物学
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DOI
PubMed
高影响因子
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