ACS Applied Materials & Interfaces
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2025
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IF 8.2
Shuying He,Yuerong Lv,Jingnan Qiu,Shudan Cui,Zixian Gao,Liang Peng
Treating metabolic dysfunction-associated fatty liver disease (MAFLD) and reducing the occurrence of MAFLD-associated liver cancer remain challenging. Two-dimensional (2D) tantalum carbide (Ta4C3) MXene nanozymes (MXenzymes) exhibit antioxidant and anti-inflammatory activities and have thus attracted considerable attention in the fields of oncology and engineering. However, the potential mechanism of action and bioactive properties of Ta4C3 in MAFLD remain uncertain. In our study, Ta4C3 not only inhibited lipid accumulation and disrupted lipid metabolism in hepatocytes but also reduced cell death caused by fatty acids by decreasing intracellular reactive oxygen species (ROS) levels, which significantly promoted the polarization of M1 macrophages to M2 macrophages by alleviating oxidative stress and further suppressing inflammatory factor expression. In mice fed a methionine–choline-deficient (MCD) diet, Ta4C3 reduced lipid accumulation, the infiltration of inflammatory cells, and liver cell apoptosis by modulating the cellular microenvironment through its anti-inflammatory and antioxidant properties. Therefore, Ta4C3 can be used as a multifunctional bioactive material to alleviate hepatic steatosis and inflammation in individuals with MAFLD/metabolic dysfunction-associated steatohepatitis (MASH) because of its robust antioxidant and anti-inflammatory effects.
研究领域:
医学
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生物材料学
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肝脏病学
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DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE BIOLOGY
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2017
·Vol. 250
·期 2
·195-204
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IF 1.696
Ma Long,Dong Jia-Xin,Wu Can,Li Xue-Yi,Chen Jing,Zhang Hong,Liu Yi
Liver mitochondria are involved in several important life processes; mitochondrial dysfunction and disorders are implicated in several human diseases. Alcohol permeates all tissues of the body and exerts some intrinsic hepatotoxicity. In this work, our results demonstrated that ethanol caused a series of mitochondria permeability transition pore (MPTP) opening factors such as mitochondrial swelling, increased permeability of H + and K + , collapsed membrane potential, and increased membrane fluidity. Furthermore, mitochondrial ultrastructure alternation observed clearly by transmission electron microscopy and the release of Cytochrome c could explain the MPTP opening from another aspect. Moreover, ethanol damaged the mitochondrial respiration system and induced disturbance of mitochondrial energy metabolism which was monitored by polarographic and microcalorimetric methods, respectively. Considered together, these damages may promote both apoptotic and necrotic cell death and contribute to the onset or progression alcohol-induced liver diseases.
研究领域:
生物化学
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医学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Jinhui Yu,Chao Liu,Mingjie Wang,Yuanyuan Liu,Liyuan Ran,Zichao Yu,Deyuan Ma,Gao Chen,Fuwen Han,Shengbo You,Yuping Bi,Yingjie Wu
Spirulina is widely known as the “Super Nutritious Food of the Future” due to its exceptional nutritional properties. In this article, we investigated the effects of fermentation using a combination of Lactobacillus acidophilus KDB-03 and Kluyveromyces marxianus GDMCC 2.119 on Spirulina. Fermentation significantly increased the total flavonoid and phenol levels in Spirulina, and enhanced the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging capacity and ferric-reducing antioxidant power. Untargeted ultra-performance liquid chromatography-electrospray tandem mass spectrometry-based metabolomics and gas chromatography-ion mobility spectrometry analysis revealed alterations in the metabolites and flavor components of fermented Spirulina (FS). Furthermore, a mice experiment demonstrated that FS could effectively alleviate metabolism-associated fatty liver disease (MAFLD) by regulating liver metabolism, intestinal flora, and facilitating communication between the liver and gut. These findings suggest that fermentation could be a innovative approach to enhance the diversity of Spirulina products, and potentially be used as a strategy for the prevention and treatment of MAFLD.
研究领域:
营养学
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微生物学
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代谢组学
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DOI
高影响因子
ENVIRONMENT INTERNATIONAL
·
2025
·
IF 9.7
Jianrong Han,Changqian Liu,Zhiyuan Chen,Fengkai Ruan,Fanzheng Xue,Lingxiao Ye,Yi Yu,Zhenghong Zuo,Chengyong He
Metabolic-associated fatty liver disease (MAFLD), linked to lipid dysregulation, poses global health risks. 2,2′,3,4,4′,5′-hexachlorobiphenyl (PCB138) is a persistent organic pollutant that poses potential threats to liver health due to its environmental persistence and bioaccumulation. Theabrown (TB), a natural compound extracted from black tea, exhibits lipid-lowering and antioxidant properties, but its protective effects on PCB138-induced liver injury have not been thoroughly investigated. Following a biphasic experimental design, juvenile male C57BL/6J mice were subjected to chronic PCB138 exposure (100 μg/kg, oral gavage every other day) for 48 weeks, with subsequent administration of TB (225 mg/kg/day) for an 8-week recovery duration. Long-term PCB138 exposure resulted in elevated liver/body weight ratio, hepatic triglyceride/cholesterol accumulation, and histopathological lipidosis, confirming MAFLD progression. Mechanistically, chronic oral exposure to PCB138 induced multi-organ dysregulation, characterized by: (i) intestinal barrier disruption, (ii) gut microbiota dysbiosis, (iii) disruption of the gut-liver bile acid axis accompanied by hepatic accumulation of lithocholic acid (LCA), taurolithocholic acid (TLCA), taurodeoxycholic acid (TDCA), and glycodeoxycholic acid (GDCA), and (iv) upregulated hepatic fatty acid synthase (FASN) expression, thereby accelerating de novo lipogenesis. TB administration for another 8 weeks attenuated these MAFLD manifestations, evidenced by mitigated hepatic lipidosis, repaired intestinal defenses, microbiota normalization, and bile acids rebalance. Using alpha mouse liver 12 (AML12) cells, we demonstrated that GDCA activated sterol regulatory element-binding protein 1 (SREBP1) expression, promoting lipogenesis. This study establishes long-term environmental PCB138 exposure as a driver of MAFLD via gut-liver axis activating lipogenic pathways and microbial-metabolic crosstalk. TB emerges as a potential protective agent by targeting bile acids-mediated SREBP1/FASN signaling, offering insights into environmental pollutant toxicity mitigation and MAFLD management.
研究领域:
环境毒理学
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肝病学
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营养科学
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微生物学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2024
·
IF 12.4
Yan-Hang Wang,Xin Chen,Yi-Zhen Bai,Peng Gao,Zhuo Yang,Qiang Guo,Ying-Yuan Lu,Jiao Zheng,Dan Liu,Jun Yang,Peng-Fei Tu,Ke-Wu Zeng
The hypothalamus plays a fundamental role in controlling lipid metabolism through neuroendocrine signals. However, there are currently no available drug targets in the hypothalamus that can effectively improve human lipid metabolism. In this study, we found that the antimalarial drug artemether (ART) significantly improved lipid metabolism by specifically inhibiting microglial activation in the hypothalamus of high-fat diet-induced mice. Mechanically, ART protects the thyrotropin-releasing hormone (TRH) neurons surrounding microglial cells from inflammatory damage and promotes the release of TRH into the peripheral circulation. As a result, TRH stimulates the synthesis of thyroid hormone (TH), leading to a significant improvement in hepatic lipid disorders. Subsequently, we employed a biotin-labeled ART chemical probe to identify the direct cellular target in microglial cells as protein kinase Cδ (PKCδ). Importantly, ART directly targeted PKCδ to inhibit its palmitoylation modification by blocking the binding of zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5), which resulted in the inhibition of downstream neuroinflammation signaling. In vivo, hypothalamic microglia-specific PKCδ knockdown markedly impaired ART-dependent neuroendocrine regulation and lipid metabolism improvement in mice. Furthermore, single-cell transcriptomics analysis in human brain tissues revealed that the level of PKCδ in microglia positively correlated with individuals who had hyperlipemia, thereby highlighting a clinical translational value. Collectively, these data suggest that the palmitoylation of microglial PKCδ in the hypothalamus plays a role in modulating peripheral lipid metabolism through hypothalamus-liver communication, and provides a promising therapeutic target for fatty liver diseases.
研究领域:
神经科学
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代谢学
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药理学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
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