INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 2
·1593
·
IF 5.6
Ji Ma,Yang Deng,Tingting Yang,Maoru Li,Jing Shang
Non-alcoholic fatty liver disease (NAFLD), defined in recent years as metabolic-associated fatty liver disease (MAFLD), is one of the most common liver diseases in the world, with no drugs on market. Esculetin (ESC) is an active compound discovered in a variety of natural products that modulates a wide range of metabolic diseases and is a potential drug for the treatment of NAFLD. In this study, we used an HCD-induced NAFLD larval zebrafish model in vivo and an FFA-induced BRL-3A hepatocyte model in vitro to evaluate the anti-NAFLD effect of ESC. Lipid lowering, anti-oxidation and anti-inflammation effects were revealed on ESC and related gene changes were observed. This study provides a reference for further study and development of ESC as a potential anti-NAFLD/MAFLD drug.Keywords:esculetin;non-alcoholic fatty liver disease;lipid-lowering;antioxidant
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
PubMed
高影响因子
Metabolites
·
2021
·Vol. 11
·期 6
·374
·
IF 4.932
Nanlin Zhu,Suling Huang,Qingli Zhang,Zhuohui Zhao,Hui Qu,Mengmeng Ning,Ying Leng,Jia Liu
The pathophysiology of nonalcoholic fatty liver disease (NAFLD) is a complex process involving metabolic and inflammatory changes in livers and other organs, but the pathogenesis is still not well clarified. Two mouse models were established to study metabolic alteration of nonalcoholic fatty liver and nonalcoholic steatohepatitis, respectively. The concentrations of metabolites in serum, liver and intestine content were measured by the AbsoluteIDQ®p180 Kit (Biocrates Life Sciences, Innsbruck, Austria). Multivariate statistical methods, pathway analysis, enrichment analysis and correlation analysis were performed to analyze metabolomic data. The metabolic characteristics of liver, serum and intestine content could be distinctly distinguished from each group, indicating the occurrence of metabolic disturbance. Among them, metabolic alteration of liver and intestine content was more significant. Based on the metabolic data of liver, 19 differential metabolites were discovered between DIO and control, 12 between DIO-CCl4and DIO, and 47 between DIO-CCl4and normal. These metabolites were mainly associated with aminoacyl-tRNA biosynthesis, nitrogen metabolism, lipid metabolism, glyoxylate and dicarboxylate metabolism, and amino metabolism. Further study revealed that the intervention of obeticholic acid (OCA) could partly reverse the damage of CCl4. The correlation analysis of metabolite levels and clinical parameters showed that phosphatidylcholines were negatively associated with serum alanine aminotransferase, aspartate aminotransferase, NAFLD activity score, and fibrosis score, while lysophosphatidylcholines, sphingomyelins, amino acids, and acylcarnitines shared the reverse pattern. Our study investigated metabolic alteration among control, NAFLD model, and OCA treatment groups, providing preclinical information to understand the mechanism of NAFLD and amelioration of OCA.Keywords:nonalcoholic fatty liver disease (NAFLD);nonalcoholic fatty liver (NAFL);nonalcoholic steatohepatitis (NASH);differential metabolites;metabolic pathways;obeticholic acid (OCA)
研究领域:
代谢组学
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肝脏疾病
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药理学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Li Luo,Huafeng Zhang,Weiliang Chen,Ziming Zheng,Zihao He,Haoyu Wang,Kaiping Wang,Yu Zhang
Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 10 7 vs. 2.13 ± 0.52 × 10 7 ) and butyrate (1.83 ± 1.31 × 10 7 vs. 6.39 ± 1.44 × 10 7 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine–choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.
研究领域:
药理学
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肝病学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
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2025
·Vol. 105
·期 4
·e70097
·
IF 3.3
Wei-fang Song,Sheng-nan Li,Rui-xin Yao,Qiu-yan Jiang,Ting Shi,Dan-dan Fan,Hai-juan Zhang,Wen-hui Zhang,Rui-jun Wang
The primary objective aims to evaluate the therapeutic efficacy of echinacoside in ameliorating hepatic steatosis and exploring its role in modulating autophagic flux through AMP-activated protein kinase (AMPK) signaling, positioning it as a potential treatment for non-alcoholic fatty liver disease (NAFLD). A well-established NAFLD rat model was employed, administering varying concentrations of echinacoside. Biochemical parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alongside liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), were measured to assess liver function. To elucidate the molecular mechanisms, western blot analyses were performed to assess the expressions of p-AMPK, total AMPK, and key autophagy markers LC-3 I/II and Beclin-1. Echinacoside significantly improved the lipid profile by lowering plasma TG, TC, and LDL-C levels while increasing HDL-C. It also reduced serum ALT, AST, and ALP activities, demonstrating hepatoprotective effects. Notably, echinacoside reversed the p-AMPK levels in NAFLD rats in a dose-dependent manner, with the highest dosage showing the strongest effect. This was accompanied by increased expression of LC-3 I/II and Beclin-1. Echinacoside is expected to be a therapeutic drug for NAFLD by activating AMPK activity and enhancing autophagy to improve liver function. These findings suggest its clinical potential, with autophagy modulation via the AMPK pathway as a possible therapeutic mechanism for NAFLD treatment.
研究领域:
药理学
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代谢生物学
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肝脏疾病研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
·
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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产品关联
DOI
PubMed
高影响因子
Heliyon
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2024
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IF 3.4
Kun Miao,Yawei Zhao,Ning Xue
The prevalence of obesity and its primary associated comorbidities, such as type 2 diabetes and fatty liver disease, has reached epidemic proportions, with no successful treatment available at present. Heat shock protein 90 (HSP90), a crucial chaperone, plays a key role in de novo lipogenesis (DNL) by stabilizing and maintaining sterol regulatory element binding protein (SREBP) activity. Kongensin A (KA), derived from Croton kongensis , inhibits RIP3-mediated necrosis, showing promise as an anti-necrotic and anti-inflammatory agent. It is not yet clear if KA, acting as an HSP90 inhibitor, can enhance hyperlipidemia, hepatic steatosis, and insulin resistance in obese individuals by controlling lipid metabolism. In this study, we first found that KA can potentially decrease lipid content at the cellular level. C57BL/6J mice were given a high-fat diet (HFD) and received KA and lovastatin through oral administration for 7 weeks. KA improved hyperlipidemia, fatty liver, and insulin resistance, as well as reduced body weight in diet-induced obese (DIO) mice, with no significant alteration in food intake. In vitro , KA suppressed DNL and reduced the amounts of mSREBPs. KA promoted mSREBP degradation via the FBW7-mediated ubiquitin-proteasome pathway. KA decreased the level of p -Akt Ser308, and p -GSK3β Ser9 by inhibiting the interaction between HSP90β and Akt. Overall, KA enhanced hyperlipidemia, hepatic steatosis, and insulin resistance by blocking SREBP activity, thereby impacting the FBW7-controlled ubiquitin-proteasome pathway.
研究领域:
药理学
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代谢生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2019
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IF 8.456
Jing Yang,Wenpeng Zhang,Hongjun Zhang,Minlin Zhong,Wenbo Cao,Zishuai Li,Xi Huang,Zongxiu Nie,Jiaming Liu,Peng Li,Xiaoxiao Ma,Zheng Ouyang
Mass spectrometry imaging (MSI) serves as a powerful tool for biological research, and laser desorption ionization (LDI) is used as a major sampling ionization method. Study of materials for LDI represents a major field in the MSI research, either for matrices in matrix-assisted LDI (MALDI) or sample substrates allowing matrix-free LDI. In this study, we developed a composite substrate using polydopamine (PDA) film to coat an antireflection (AR) surface for LDI-MSI. The AR material has been previously shown to confine UV energy within the micro-/nanostructures, leading to a highly localized temperature rise to facilitate analyte thermal desorption. PDA coating on the AR material further enhances the light-to-heat conversion and improves the contact between the substrate surface and the biological sample materials. With this substrate, desorption and ionization of lipids from raw human plasma samples and biological tissue sections have been achieved. Matrix-free LDI-MSI of around 30 lipid species in mouse brain sections was achieved with a significantly simplified MSI procedure at a spatial resolution of 50 μm. This method was applied to determine mouse fatty liver disease through monitoring the abundances and distributions of triacylglycerols and glycerophospholipids. Dramatic differences in the lipid profiles were subsequently identified between the liver tissues from the wild-type and obese mice.
研究领域:
分析化学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
Pharmaceutics
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2025
·Vol. 17
·期 4
·480
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IF 5.5
Kyeong-Ju Lee,Seong-Bin Yang,Jae-Hyeon Lee,Bison Seo,Hyung-Sik Won,Jooho Park
Background: Fatty liver disease and obesity are among the most prevalent health conditions in modern society and have recently garnered significant attention. Semaglutide, a well-known anti-obesity drug, has been widely used for diabetes and obesity treatment; however, nanotherapeutics utilizing semaglutide have not yet been developed.Methods: A novel statin–lipid conjugate was synthesized using rosuvastatin and ursodeoxycholic acid, a liver-protective agent. This conjugate was then formulated with semaglutide through hydrophobic interactions to create a new nanoparticle system. The physicochemical properties of the nanoparticles were analyzed, and their therapeutic efficacy was evaluated in a high-fat diet (HFD)-induced animal model.Results: The statin–lipid conjugate was successfully synthesized, forming novel nanoparticles with semaglutide in an aqueous solution. These nanoparticles exhibited distinct properties compared to conventional semaglutide formulations. In animal experiments, the treatment group demonstrated a 30.24% reduction in body weight and a 46.80% improvement in liver function markers compared to the control group.Conclusions: This study introduces a novel semaglutide-based nanoparticle (SRLC NP) system that overcomes key limitations of conventional semaglutide therapy by providing enhanced bioavailability, extended circulation time, and improved cellular uptake. These findings highlight the potential of SRLC NPs as a clinically translatable nanotherapeutic approach for more effective, sustained, and patient-friendly obesity and fatty liver disease treatment.
研究领域:
药学
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生物医学工程
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代谢疾病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ANIMAL SCIENCE
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2024
·
IF 2.7
Liu Jie,Zhang Ke,Zhao Mindie,Chen Liang,Chen Huimin,Zhao Yulan,Zhao Ruqian
The aim of this study was to investigate the alleviating effects and mechanisms of bile acids (BA) on corticosterone-induced fatty liver in broiler chickens. Male Arbor Acres chickens were randomly divided into three groups: control group (CON), stress model group (CORT), and BA-treated group (CORT-BA). The CORT-BA group received a diet with 250 mg/kg BA from 21 days of age. From day 36 to 43, both the CORT and CORT-BA groups received subcutaneous injections of corticosterone to simulate chronic stress. The results indicated that BA significantly mitigated the body weight loss, liver enlargement, and hepatic lipid deposition caused by corticosterone (P < 0.05). Liver RNA-seq analysis showed that BA alleviated corticosterone-induced fatty liver by inhibiting lipid metabolism pathways, including fatty acid biosynthesis, triglyceride biosynthesis, and fatty acid transport. Additionally, BA improved corticosterone-induced downregulation of glucocorticoid receptor (GR) expression (P < 0.05). Molecular docking and cellular thermal shift assays revealed that hyodeoxycholic acid (HDCA), a major component of compound bile acids, could bind to GR and enhance its stability. In conclusion, BA alleviated corticosterone-induced fatty liver in broilers by inhibiting lipid synthesis pathways and mitigating the suppression of hepatic GR expression.
研究领域:
动物科学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
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2025
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IF 10.5
Mengdi Zhang,Jinliang Ji,Yuanyuan Lei,Fujian Qin,Yitong Tao,Ning Li,Jinlei Bian,Zhiyu Li,Maode Lai,Zhixia Qiu
Inhibiting de novo lipogenesis (DNL) in hepatocytes is a promising strategy for treating metabolic fatty liver diseases. ACLY, a key enzyme in the DNL pathway, has become a therapeutic target for non-alcoholic fatty liver disease (NAFLD). However, its inhibition shows mixed outcomes, depending on interventions and diets. Evidence suggest ACLY inhibition activates the ACSS2-mediated acetate metabolism and the subsequent DNL, though potential mechanisms and possible consequences remain unclear. This study found that targeting hepatic ACLY with AAV8-shRNA failed to improve NAFLD in mice fed a high-fat, high-fructose diet. Instead, it worsened inflammation and liver injury. ACLY inhibition conditionally upregulated DNL enzymes, but consistently activated the ACSS2-acetyl-CoA pathway and suppressed fatty acid oxidation. Further, ACLY inhibition led to polyunsaturated fatty acid accumulation, triggering mitochondrial dysfunction. The resulting ROS redirected carbon flux into acetate, activating the ACSS2-acetyl-CoA pathway, which promoted lipid biosynthesis and exacerbated mitochondrial dysfunction—a vicious cycle that fueled inflammation and liver damage. Dual inhibition of ACLY and ACSS2 broke this cycle by reducing hepatic acetyl-CoA flux, suppressing DNL, enhancing fatty acid oxidation via PPAR-α activation, and improving mitochondrial function. This combined targeting strategy reduced lipid accumulation, alleviated inflammation, and normalized aminotransferase levels, effectively reversing NAFLD progression.
研究领域:
生物化学
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代谢疾病
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肝脏研究
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Qian Wang,Dongmei Li,Ze Zhang,Lingyi Shen,Hong Xu,Zhiyong Wang,Carl Redshaw,Qilong Zhang
Non-alcoholic fatty liver disease (NAFLD) is a disease closely associated with metabolic abnormalities. Lipid droplets (LDs) serve as organelles that store intracellular neutral lipids and maintain cellular energy homeostasis. Their abnormalities can cause metabolic disorders and disease, which is also one of the distinctive characteristics of NAFLD patients. However, the correlation between the polarity of LDs and NAFLD is easily overlooked. To monitor the polarity changes in LDs in order to assess the progression of NAFLD, triphenylamine was used as the electron donor (D), pyridine as the electron acceptor (A) and thiazolo[5,4-d]thiazole (TTz) as π bridge in this study. The structure was modified by introducing different substituents at the triphenylamine to obtain a series of D-π-A structural polar-responsive asymmetric thiazolo[5,4-d]thiazole (aTTz) fluorescent probes with different push–pull electron effects and steric hindrance. The fluorescent probes, which exhibit distinct fluorescence emission spectra in solutions with varying polarities, demonstrate excellent polarity-sensitive properties, and the displacement of the maximum emission wavelength varies from 125 to 150 nm. Meanwhile, the fluorescent probes exhibited low dark toxicity of cells and can specifically image lipid droplets, with a localization coefficient of more than 0.84 when imaging, and can be applied to the fluorescence imaging of C. elegans . Furthermore, the polar response properties of the fluorescent probes were used to distinguish normal liver tissue and nonalcoholic fatty liver tissue by fluorescence lifetime microscopic imaging (FLIM), thus providing a molecular tool for the diagnosis of NAFLD.
研究领域:
生物化学
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医学影像学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2021
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IF 4.24
Fan Yang,Bo Feng,Yong Jie Niu,Ching Yuan Hu,Yong Hong Meng
Fatty liver disease is a global public health threat. Fu instant tea is a new tea product made from the Fu brick tea fermented by Eurotium cristatum . This study explored Fu instant tea's effects on improving fatty liver disease and intestinal microbiota dysbiosis caused by a high-fat diet. We found that Fu instant tea's production process increased polyphenols content from 36.3 ± 1.4 mg/g to 111 ± 6 mg/g, and the Fu instant tea had higher antioxidant activity than Fu brick tea. More importantly, Fu instant tea prevented fatty liver disease by reducing liver edema and reduced liver fat accumulation and inflammation. Meanwhile, Fu instant tea also reduced the ratio of the Firmicutes / Bacteroidetes that decreased energy intake. Fu instant tea increased the abundance of Bifidobacterium , Lactobacillus , Ruminococcaceae , and Lachnospiraceae and reduced Helicobacter and Desulfovibrio , contributing to inhibiting liver inflammation. Fu instant tea also increased the short-chain fatty acids, which indirectly contributed to increasing intestinal epithelial cells' growth, which helped prevent fatty liver disease. Our results demonstrate the health function of Fu instant tea and support the development of other tea products.
研究领域:
营养学
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微生物学
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食品科学
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DOI
高影响因子
危险品化学品经营许可证（带存储）