ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2022
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IF 4.114
Pan Li,Yuwei Chen,Xiumei Ke,Ruoyu Zhang,Ling Zuo,Meng Wang,Zhiwei Chen,Xianqin Luo,Jianwei Wang
Baicalin is a flavonoid compound abundant in multiple edible and medicinal plants such as Scutellaria baicalensis Georgi . In this study, we provide evidence to support the fact that baicalin ameliorates alcohol-induced hepatic steatosis via regulating SREBP1c elicited PNPLA3 competitive binding to ATGL . Results showed that baicalin significantly attenuated the development of metabolic disorders and hepatic steatosis in alcohol-induced rats after four weeks of treatment. It was evident that baicalin treatment significantly normalized the serous contents of hepatic triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and attenuated the increase of hepatic vacuolization and Oil Red O staining area caused by alcohol. Meanwhile, baicalin relieves alcohol-induced hepatic fibrosis by masson staining and RT-qPCR analysis. Mechanistically, alcohol aggravated the nuclear expression of SREBP1c, which contributed to the high expression of PNPLA3 and FASN , thereby enhancing the binding of PNPLA3 to ABHD5 , and indirectly impairing the binding ability between ATGL and ABHD5, ultimately causing a decline in the hydrolysis capacity in liver lipid droplets . As expected, these alcohol-induced pathobolism were reversed by baicalin treatment both in vivo and in vitro . In conclusion, this study has demonstrated that baicalin can protect against alcohol-induced hepatic lipid accumulation by activating hepatic lipolysis via suppressing SREBP1c elicited PNPLA3 competitive binding to ATGL. Baicalin is a promising natural product for preventing alcohol-induced hepatic steatosis.
研究领域:
药理学
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肝病学
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代谢学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULES
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2018
·Vol. 23
·期 7
·1654
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IF 3.098
Xiaozhi Qiao,Yunlan Li,Jiaqi Mai,Xiaoqing Ji,Qingshan Li
Dibutyltin dilaurate (DBTD) has multiple applications in daily life. However, DBTD is easily deposited in the liver and affects liver functions. This study was designed to explore the effects of DBTD on triglyceride metabolism in human normal hepatocyte HL7702 cells. Our results showed that the intracellular fat contents were dose-dependently decreased by DBTD. The expression of lipolysis genes and proteins were elevated while the lipogenesis genes and proteins were diminished by DBTD. The phosphorylation levels of ribosomal S6 kinase 1 were reduced by both rapamycin and DBTD, indicating that the mTOR pathway was suppressed possibly. The decreased sterol regulatory element-binding protein 1C (SREBP1C) transcription levels, as well as the increased peroxisome proliferator-activated receptor alpha (PPARα) transcription levels, caused by rapamycin and DBTD corresponded to the inactive mTOR pathway. In conclusion, it was possible that DBTD reduced the intracellular triglyceride through depressing the mTOR pathway and affecting its downstream transcription factors.Keywords:dibutyltin dilaurate (DBTD);triglycerides metabolism;mTOR pathway;SREBP1C;PPARα
研究领域:
毒理学
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细胞生物学
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代谢研究
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DOI
PubMed
高影响因子
Nature Communications
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2026
·Vol. 17
·期 1
·2821
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IF 18.1
Xiao Hai-Tao,Song Peng,Jin Jing,Wang Yong-Dan,Xu Yin-Yue,Wu He,Shao Xue-Xue,Gan Qi-Feng,He Jian,Wen Yan-Rong,Zhu Jing,Chen Bao-Yi,Zhou Ping,Lai Li-Na,Yang Hua,Li Ping,Zheng Zu-Guo
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern that affects nearly one-quarter of the world’s population. General control non-repressed protein 5 (GCN5), a histone acetyltransferase (HAT), has been implicated in the progression of several diseases, but its role in MASLD remains unclear. Here, we provide the experimental evidence that progressive human and male murine MASLD is driven by GCN5, but not by p300/CREB binding protein associated factor (PCAF) activation. Hepatocyte-specific GCN5 overexpression accelerates MASLD progression, whereas its ablation alleviates disease severity. Moreover, pharmacological inhibition of GCN5 with CPTH2 protects against MASLD. Metabolomics and RNA-seq analyses demonstrate that GCN5 promotes de novo lipogenesis (DNL) by upregulating SREBP1c-mediated transcription of lipogenic genes. Mechanistically, GCN5 acetylates histone H3 at the SREBP1c promoter, enhancing transcription through its intrinsic acetyltransferase activity. Our findings further identify GCN5 as a key regulator of LXRα-induced SREBP1c expression, suggesting that targeting GCN5 may selectively inhibit SREBP1c-driven DNL without impairing LXRα-mediated reverse cholesterol transport (RCT). Notably, combined treatment with the Liver X Receptor (LXR) agonist T0901317 and CPTH2 synergistically reduced lipid accumulation in vitro and in vivo, highlighting a promising therapeutic strategy for MASLD.
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DOI
PubMed
高影响因子
Chinese Medicine
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2026
·Vol. 21
·期 1
·223
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IF 7.4
Liang Hui-Mei,Xu Yin-Yue,Miao Kun,Xiao Hai-Tao,Wang Yong-Dan,Jin Jing,Wu He,Chen Bao-Yi,Xu Li-Jun,Zhu Jiang-Ping,Lai Li-Na,Zheng Zu-Guo
Background Astragaloside IV (AS-IV), a bioactive saponin from Astragalus membranaceus, shows promise for treating metabolic dysfunction-associated steatotic liver disease (MASLD), though its mechanisms remain unclear. Purpose This study aimed to elucidate how AS-IV alleviates hepatic steatosis, specifically investigating its epigenetic regulation of lipogenesis. Methods Using high-fat diet-fed mice and lipids-loaded hepatocytes, we assessed AS-IV's effects through SREBP-1c overexpression, histone acetylation analysis, and GCN5 rescue experiments. Results AS-IV significantly reduced hepatic steatosis by suppressing SREBP-1c-mediated de novo lipogenesis. Mechanistically, it inhibited histone acetyltransferase GCN5, decreasing H3K9/H3K14 acetylation at the SREBP-1c promoter and attenuating LXRα-driven transcription. GCN5 overexpression reversed AS-IV's suppression of SREBP-1c and lipid accumulation. Conclusion AS-IV uniquely downregulates GCN5 expression at the transcriptional level, exerting epigenetic regulation to disrupts lipogenic programming, This represents a novel multi-target approach against MASLD that connects natural product pharmacology with epigenetic modulation.
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DOI
高影响因子
JOURNAL OF DAIRY SCIENCE
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2023
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IF 3.5
Shendong Zhou,Mengru Chen,Meijuan Meng,Nana Ma,Wan Xie,Xiangzhen Shen,Zhixin Li,Guangjun Chang
ABSTRACT Ketosis is a metabolic disease that often occurs in dairy cows postpartum and results from disordered lipid metabolism. Acetyl-coenzyme A (CoA) acetyltransferase 2 ( ACAT2 ) is important for balancing cholesterol and triglyceride ( TG ) metabolism; however, its role in subclinical ketotic dairy cows is unclear. This study aimed to explore the potential correlation between ACAT2 and lipid metabolism disorders in subclinical ketotic cows through in vitro and in vivo experiments. In the in vivo experiment, liver tissue and blood samples were collected from healthy cows ( CON , n = 6, β-hydroxybutyric acid [ BHBA ] concentration < 1.0 mM) and subclinical ketotic cows (subclinical ketosis [ SCK] , n = 6, BHBA concentration = 1.2–3.0 mM) to explore the effect of ACAT2 on lipid metabolism disorders in SCK cows. For the in vitro experiment, bovine hepatocytes ( BHEC ) were used as the model. The effects of BHBA on ACAT2 and lipid metabolism were investigated via BHBA concentration gradient experiments. Subsequently, the relation between ACAT2 and lipid metabolism disorder was explored by transfection with siRNA of ACAT2. Transcriptomics showed an upregulation of differentially expression genes ( DEGs ) during lipid metabolism and significantly lower ACAT2 mRNA levels in the SCK group. Compared with the CON group in vivo, the SCK group showed significantly higher expression levels of peroxisome proliferator–activated receptor γ ( PPARγ ) and sterol regulator element binding protein 1c ( SREBP1c ) and significantly lower expression levels of peroxisome proliferator-activated receptor α ( PPARα ), carnitine palmitoyl-transferase 1A ( CPT1A ), sterol regulatory element binding transcription factor 2 ( SREBP2 ), and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ). Moreover, the SCK group had a significantly higher liver TG content and significantly lower plasma total cholesterol ( TC ) and free cholesterol ( FC ) content. These results were indicative of TG and cholesterol metabolism disorders in the liver of dairy cows with SCK. Additionally, the SCK group showed an increased expression of Perilipin-2 ( PLIN2 ), decreased expression of apolipoprotein B ( APOB ), and decreased plasma concentration of very low-density lipoproteins ( VLDL ) and low-density lipoproteins-cholesterol ( LDL-C ) by downregulating ACAT2, which indicated an accumulation of TG in liver. I n vitro experiments showed that BHBA induced an increase in the TG content of BHEC, decreased content TC, increased expression of PPARγ and SREBP1c, and decreased expression of PPARα, CPT1A, SREBP2, and HMGCR. Additionally, BHBA increased the expression of PLIN2 in BHEC, decreased the expression and fluorescence intensity of ACAT2, and decreased the VLDL and LDL-C contents. Furthermore, silencing ACAT2 expression increased the TG content; decreased the TC, VLDL, and LDL-C contents; decreased the expression of HMGCR and SREBP2; and increased the expression of SREBP1c; but had no effect on the expression of PLIN2. These results suggest that ACAT2 downregulation in BHEC promotes TG accumulation and inhibits cholesterol synthesis, leading to TG and cholesterol metabolic disorders. In conclusion, ACAT2 downregulation in the SCK group inhibited cholesterol synthesis, increased TG synthesis, and reduced the contents of VLDL and LDL-C, eventually leading to disordered TG and cholesterol metabolism.
研究领域:
兽医学
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分子生物学
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生物化学
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动物生理学
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DOI
PubMed
高影响因子
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