BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Chunmeng Ding,Zhenguo Shen,Ruonan Xu,Yajing Liu,Mengyue Xu,Chenyu Fan,Dongyue Hu,Tian Xing
Aim To investigate the impact of exosomes released by Porphyromonas gingivalis -Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. Results The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. Conclusions In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis.
研究领域:
分子生物学
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细胞生物学
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病理学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2026
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IF 5.4
Fang Wang,Yan Qing Liu,Jun Nan Wei,Xiao Fen Wang,Feng Qin Li,Xiu Jia Tian,Dan Li,Yu Xuan Gao,Xin Zhi Guo,Xue Yan Li,Ping Luo
Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder characterized by intrahepatic lipid accumulation, oxidative stress, and inflammatory responses, underscoring the urgent need for effective therapeutic strategies. D-limonene, a cyclic monoterpenoid primarily derived from citrus fruits, possesses well-documented antioxidant, anti-fibrotic, and wound-healing properties. However, its therapeutic potential in MASLD remains largely unexplored. Methods To evaluate the therapeutic efficacy of D-limonene, a rat model of MASLD was established using a high-fat diet (HFD). An integrated approach combining metabolomics, transcriptomics, and network analysis was employed to identify key signaling pathways and molecular targets. The expression levels of candidate targets were validated by RT-qPCR and Western blotting. Molecular docking simulations were performed to predict the binding affinity between D-limonene and the target proteins. Furthermore, a cellular thermal shift assay (CETSA) was conducted to confirm direct binding and protein stabilization. In parallel, cellular experiments using BRL-3A and HepG2 cells were carried out to assess the effect of D-limonene on lipid accumulation. Results D-limonene treatment significantly ameliorated liver injury, reduced excessive lipid deposition, attenuated inflammation, and suppressed oxidative stress in HFD-induced rats. Integrated multi-omics and network analyses identified the PPAR signaling pathway as the core pathway mediating the regulatory effects of D-limonene on lipid metabolism, with PPARγ and SCD-1 pinpointed as key downstream targets. RT-qPCR and Western blot analyses confirmed that D-limonene significantly downregulated the expression of both PPARγ and SCD-1. Molecular docking simulations revealed stable binding of D-limonene to PPARγ and SCD-1. Importantly, CETSA further demonstrated that D-limonene directly binds to and stabilizes these two proteins. Consistently, cellular assays showed that D-limonene significantly reduced lipid accumulation in BRL-3A and HepG2 cells by inhibiting the PPARγ/SCD-1 axis. Conclusion Collectively, these findings suggest that D-limonene alleviates HFD-induced MASLD, and its protective effects may be mediated, at least in part, through inhibition of the PPARγ/SCD-1 axis. This study provides preliminary evidence supporting the potential development of D-limonene as a targeted therapeutic agent for MASLD. Further studies are warranted to validate these findings and elucidate additional underlying mechanisms.
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2023
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IF 5.6
Ritian Jin,Jude Juventus Aweya,Rong Lin,Wuyin Weng,Jiaqi Shang,Dangfeng Wang,Yiling Fan,Shen Yang
VLATSGPG (VLA) was a DPP-IV inhibitory peptide isolated from salmon ( Salmo Salar ) skin. Here, we demonstrated that VLA inhibited the activation of PERK through the AKT signaling pathway. Furthermore, we investigated the effect of VLA on free fatty acid (FFA)-induced lipid accumulation disorder and inflammation in HepG2 cells, elucidating the potential regulatory mechanism in this nonalcoholic fatty liver disease cell model. VLA reduced the mRNA expression of adipogenic factors FAS, ACC, and SCD-1 through the PERK/eIF2α pathway and the level of apolipoprotein B-100 secretion. These may contribute to the reducing FFA-induced lipid accumulation in cells and reducing intracellular lipid levels. In addition, VLA increased IκBα mRNA expression via the PERK/IκBα pathway, inhibited the NF-κB p65 activation, and thus inhibited cell inflammation.
研究领域:
分子生物学
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细胞生物学
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药理学
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生物化学
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DOI
高影响因子
Chinese Herbal Medicines
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2019
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IF 0
Ya-yun Liu,Jiao-jiao You,Wei Xu,Ting Zhai,Chun-yuan Du,Yong Chen,Feng-mei Han
Objective The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens (GPAE) against nonalcoholic steatohepatitis (NASH) in mice and NCTC-1469 cells. Methods C57BL/6J mice were fed with methionine and choline-deficient (MCD) diet and administered simultaneously with GPAE (500 and 1000 mg/kg/d, respectively) by gavage for six weeks. The biomarkers of NASH in serum and liver were determined. NCTC-1469 cells were pretreated with 0.25 mmol/L palmitic acid (PA) plus 0.5 mmol/L oleic acid (OA) for 24 h or treated with adenovirus expressing short-hairpin RNA against CFLAR (Ad-shCFLAR) for 24 h and then treated with GPAE (80 and 160 µg/mL, respectively) for 24 h, and the content of cellular biomarkers of NASH was detected. Results In mice treated with MCD , GPAE could decrease the levels of serum ALT , AST, the content of hepatic TG , TC and MDA , repress the activities and protein expression of CYP2E1 and CYP4A and the phosphorylation of JNK, increase the activities of HO-1, CAT and GSH-Px, up-regulate the mRNA expression of PPARα, FABP5, CPT1α, ACOX, SCD-1, mGPAT, MTTP and the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with PA and OA, GPAE could decrease the content of cellular TG and ROS , promote the uptake of 2-NBDG, up-regulate the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with Ad-sh CFLAR , GPAE up-regulated the mRNA and protein expression of CFLAR, down-regulated the phosphorylation of JNK, and increased the protein expression of NRF2 and pIRS1 . Conclusion These results indicated that the activation on CFLAR-JNK pathway might be the main anti-NASH mechanism of GPAE, which on the one hand promote the β-oxidation and efflux of fatty acids in liver, and finally reduce hepatic lipid accumulation , on the other hand increase the activities of anti-oxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2, and therefore attenuates hepatic oxidative stress damage.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
危险品化学品经营许可证（带存储）