PHYTOMEDICINE
·
2025
·
IF 8.3
Yingya Zhou,Meng Feng,Hongyan Hai,Xinmeng Teng,Xinxin Zhou,Yong Gao,Yanhua Zhong,Changhui Liu
Background : Due to the absence of disease-modifying treatments and mysterious molecular causes, metabolic dysfunction-associated steatotic liver disease (MASLD) poses an urgent and unmet clinical need. The active ingredient in Fructus gardenia , geniposidic acid (GPA), has anti-inflammatory, antioxidant, and hepato-protective properties. However, its effects on MASLD are still unknown. Purpose : This study aimed to determine how diet-induced hepatic steatosis in mice is affected by GPA. Methods : Dietary induction developed the mouse model of hepatic steatosis. The influence of GPA on hepatic steatosis, inflammation, and fibrosis were examined using the mouse primary hepatocyte lipid overload model. The mechanism of GPA in preventing and treating MASLD was explored through RNA-seq, and the activation of the SIRT6 signal by GPA was verified by molecular docking, pull-down, etc. Hepatocyte-specific Sirt6 -deletion mice were established, and cellular and animal studies were performed to assess SIRT6 functions in inhibiting and treating MASLD by GPA. Results : GPA therapy significantly enhanced hepatic fat accumulation, oxidative stress, inflammatory infiltration, and fibrosis in mice subjected to high fat diet (HFD) and methionine choline deficient (MCD) diets. In the meantime, GPA can reduce oxidative stress in hepatocyte metabolic stress and fat buildup brought on by oleic acid (OA) and palmitic acid (PA). RNA sequencing revealed that GPA exerts its protective effects against MASLD primarily by stimulating SIRT6 and triggering the downstream PPARα signaling cascade. Furthermore, GPA was found to interact directly with SIRT6 through specific binding sites. This interaction enables SIRT6 activation under both normal and disease conditions. However, without SIRT6, the liver-protective benefits of GPA under metabolic stress are lost. Conclusion : It was found that GPA binds directly to SIRT6 and enhances its activity, thereby inhibiting the progression of diet-induced MASLD. The findings suggest the potential of GPA as a therapeutic target for treating MASLD.
研究领域:
药理学
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分子生物学
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肝病学
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营养学
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药物研发
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Peng Ma,Rongrong Huang,Yu Ou
Soy glycinin derived octapeptide (SGP8) is a peptide obtained from degradation of the soy glycinin, whose amino acid sequence is IAVPGEVA. To determine the effect of SGP8 on non-alcoholic fatty liver disease (NAFLD), steatosis HepG2 cells were induced by 1 mmol/L free fatty acid (FFA) and C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 3 weeks to establish NAFLD model. The results of oil red O staining and total cholesterol (TC)/triglyceride (TG) contents showed that SGP8 could significantly reduce the lipid content of steatosis HepG2 cells. In vivo , SGP8 lowered plasma alanine aminotransferase (ALT) and low density lipoprotein (LDL) content, normalized hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) production, and reduced the severity of liver inflammation. The results of Western blotting showed that SGP8 increased expression of Sirtuin-1 (SIRT1) and phosphorylation level of AMP activated protein kinase (AMPK) in hepatocytes. Through activation of SIRT1/AMPK pathway, SGP8 downregulated the expression of sterol regulatory element binding protein 1c (SREBP-1c) and its target genes ACC and FAS expression levels, and increased the phosphorylation level of acetyl CoA carboxylase (ACC). Furthermore, SGP8 also upregulated the expression of transcription factor peroxisome proliferator activated receptor α (PPARα), which was regulated by SIRT1/AMPK pathway, and its target gene CPT1 level. In conclusion, SGP8 might improve NAFLD by activating the SIRT1/AMPK pathway. Our data suggest that SGP8 may act as a novel and potent therapeutic agent against NAFLD.
研究领域:
药理学
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分子生物学
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肝病学
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Ruiqian Duan,Xiao Guan,Kai Huang,Yu Zhang,Sen Li,Ji’an Xia,Meng Shen
A high-fat diet (HFD) causes hyperlipidemia, which worsens disturbances in bile acid (BA) metabolism and gut microbiota. This study aimed to investigate the regulation of flavonoids from whole-grain oat (FO) on BA metabolism and gut microbiota in HFD-induced hyperlipidemic mice. The experiment results showed that FO improved serum lipid profiles and decreased body weight and lipid deposition in HFD-fed mice. Through real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot assays, by up-regulating the expression of PPARα, CPT-1, CYP7A1, FXR, TGR5, NTCP, and BSTP, and down-regulating those of SREBP-1c, FAS, and ASBT, FO suppressed lipogenesis, promoted lipolysis and BA synthesis, and efflux to faeces via the FXR pathway. 16s rRNA sequencing revealed that FO significantly increased Akkermansia and significantly decreased Lachnoclostridium, Blautia, Colidextribacter, and Desulfovibrio. Spearman’s correlation analysis showed that these bacteria were strongly correlated with hyperlipidemia-related parameters. Therefore, our results indicated that FO possessed an antihyperlipidemic effect via regulating the gut–liver axis, i.e., BA metabolism and gut microbiota.
研究领域:
营养学
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生物化学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yang Chang,Yafei Xia,Xiaojun Liu,Putian Yu,Furong Fan,Yangyang Shi,Shixin Yan,Shu Yan
Background Cholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism. Methods α-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined. Results The intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D -lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH. Conclusions QRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.
研究领域:
药理学
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肝病学
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代谢组学
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微生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 24
·期 9
·5168-5184
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IF 4.486
Huan Nie,Yuanjun Deng,Chuiyang Zheng,Maoxing Pan,Jiqian Xie,Yupei Zhang,Qinhe Yang
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is still not fully understood, and currently, no effective pharmacotherapy is available. Nuclear receptors (NRs) are important biological participants in NAFLD that exhibit great therapeutic potential. Chaihu Shugan powder (CSP) is a traditional Chinese medicine (TCM) formula that has a wide therapeutic spectrum including NAFLD, but the effective components and functional mechanisms of CSP are unclear. We adopted a network pharmacology approach using multiple databases for Gene Ontology (GO) enrichment analysis and the molecular complex detection (MCODE) method for a protein-protein interaction (PPI) analysis, and we used molecular docking method to screen the NR targets and determine the corresponding CSP components. The screening results were validated through a NAFLD rat model that was used to explain the possible relationship between CSP and NAFLD. Finally, we screened PPARγ, FXR, PPARα, RARα and PPARδ as target genes and quercetin , kaempferol , naringenin , isorhamnetin and nobiletin as target compounds. The five components were detected through high-performance liquid chromatography-mass spectrometry (HPLC-MS), the results of which aligned with the docking experiments of PPARγ, PPARα and PPARδ. After CSP intervention, the NAFLD rat model showed ameliorated effects in terms of bodyweight, hepatic histopathology, and serum and liver lipids, and the mRNA levels of PPARγ, FXR, PPARα and RARα were significantly changed. The results from this study indicate that CSP exhibits healing effects in an NAFLD model and that the network pharmacology approach to screening NR targets and determining the corresponding CSP components is a practical strategy for explaining the mechanism by which CSP ameliorates NAFLD.
研究领域:
药理学
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中药学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
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
✓ 已验证
产品关联
DOI
Frontiers in Pharmacology
·
2022
·
IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
研究领域:
药理学
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代谢学
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胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Jing Song,Fengyun Huang,Kun Ma,Rui Ding,Kai Tan,Dan Lv,Kiyoshi Soyano,Kai Zhao
Bifenthrin (BF) is a broad-spectrum insecticide that has gained widespread use due to its high effectiveness. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. This study aimed to investigate the 50 % lethal concentration (LC 50 ) and safety concentration of Chinese giant salamanders (CGS) exposed to BF (at 0, 6.25,12.5,25 and 50 μg/L BF) for 96 h. Subsequently, CGS were exposed to BF (at 0, 0.04, and 4 μg/L BF) for one week to investigate its toxic effects. Clinical poisoning symptoms, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results indicate that exposure to BF at 4 μg/L significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) contents in the brain, liver, and kidney of CGS. Additionally, the study found that the malondialdehyde (MDA), reactive oxygen species (ROS), and 8-hydroxydeoxyguanosine (8-OHdG) contents were increased. The liver tissue exhibited significant inflammatory reactions and structural malformations. RNA-seq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS. This affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior, and detoxification, which were significantly upregulated, resulting in the differential genes significantly enriched in the calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. The results suggest that BF induces the abnormal production of free radicals, which overwhelms the body's self-defense system, leading to varying degrees of oxidative stress. This can result in oxidative damage, DNA damage, abnormal lipid metabolism, autoimmune diseases, clinical poisoning symptoms, and tissue inflammation. This work provides a theoretical basis for the rational application of bifenthrin and environmental risk assessment, as well as scientific guidance for the conservation of amphibian populations.
研究领域:
环境毒理学
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两栖生物学
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分子生物学
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生态毒理学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 12
·10876-10885
·
IF 4.171
Xiong Li,Shiming Huang,Xi Chen,Qijun Xu,Yongxuan Ma,Lijun You,Viktoryia Kulikouskaya,Jianbo Xiao,Jinhua Piao
A sulfated polysaccharide extracted from Gracilaria lemaneiformis (GLP) with a prominent effect in regulating lipid metabolism was isolated. The molecular weight was 31.5 kDa and it was composed mainly of galactose, glucose and xylose. Fourier-transform infrared (FT-IR) spectrum and nuclear magnetic resonance (NMR) analysis suggested that GLP was composed of the following repeating unit: [3-β-Gal-4(OSO3)-1→4-α-3,6-anhydrogal-2(OSO3)-1→]. GLP could significantly decrease serum total cholesterol, triglyceride and free fatty acid levels and lower alanine aminotransferase and aspartate aminotransferase activities in high-fat-diet mice. Additionally, GLP could keep the body weight and attenuate accumulation of fat surrounding the liver and epididymis induced by high-fat diet. Results of RT-PCR indicated that GLP might regulate lipid metabolism and accelerate free fatty acid oxidation by up-regulating the expression of the PPARα, ACS and CPT1a gene. The present study suggests that GLP may be potentially useful for regulating lipid metabolism.
研究领域:
海洋生物学
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Li Guangquan,Wang Xianze,Liu Yi,Gong Shaoming,Yang Yunzhou,Wang Cui,Wang Huiying,He Daqian
Bile acids(BAs) are important components of bile and play a significant role in fat metabolism. However, there is currently no systematic evaluation of the use of BAs as feed additives for geese.This study aimed to investigate the effects of adding BAs to goose feed on growth performance, lipid metabolism, intestinal morphology, mucosal barrier function, and cecal microbiota. A total of 168 28-day-old geese were randomly assigned to four treatment groups and fed diets supplemented with 0, 75, 150, or 300 mg/kg of BAs for 28 days. The addition of 75 and 150 mg/kg of BAs significantly improved the feed/gain (F/G) (p < 0.05).The addition of BAs decreased abdominal fat percentage and serum total cholesterol (TC) levels, with 150 mg/kg of BAs significantly reducing serum triglyceride levels and increased expression of Farnesoid X Receptor (FXR) mRNA in the liver(p < 0.05), 300 mg/kg of BAs significantly increasing the expression level of liver peroxisome proliferator-activated receptor α (PPARα) (p < 0.05). In terms of intestinal morphology and mucosal barrier function, 150 mg/kg of BAs significantly increased villus height (VH) and VH/crypt depth (CD) in the jejunum (p < 0.05). The addition of 150 and 300 mg/kg of BAs significantly reduced the CD in the ileum, while increasing VH and VH/CD (p<0.05). Additionally, the addition of 150 and 300 mg/kg of BAs significantly increased the expression levels of zonula occludens-1 (ZO-1) and occludin in the jejunum. Simultaneously 150mg/kg and 300mg/kg BAs increased the total short-chain fatty acids (SCFA) concentrations in the jejunum and cecum(p < 0.05).Supplementation with BAs resulted in a significant increase in the ɑ-diversity of cecal microbiota and a decrease in the abundance of Proteobacteria in the cecum. The addition of 150 mg/kg of BAs significantly reduced the abundance of Bacteroidetes and increased the abundance of Firmicutes. Moreover,Linear discriminant analysis Effect Size analysis (LEfSe) showed that the abundances of bacteria producing SCFA and bile salt hydrolases (BSH) were increased in the BAs-treated group. Furthermore, Spearman’s analysis showed that the genus Balutia, which is negatively correlated with visceral fat area, was positively correlated with serum high-density lipoprotein cholesterol (HDL-C), while Clostridium was positively correlated with intestinal VH and VH/CD. In conclusion, BAs can be considered an effective feed additive for geese, as they increased SCFA concentration, improve lipid metabolism and intestinal health by enhancing the intestinal mucosal barrier, improving intestinal morphology, and altering the cecal microbiota structure.
研究领域:
动物科学
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营养学
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微生物学
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代谢学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMB Express
·
2024
·Vol. 14
·期 1
·1-16
·
IF 3.5
Yan Yan,Yuan Haisheng,Yang Fan,Na Heiya,Yu Xiuling,Liu Jingran,Wang Yuzhen
Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn ( Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 ( B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold ( P < 0.05) and 2.3 folds ( P < 0.05), respectively, while the CPT1α and PPARα mRNA levels was significantly increased by 2.3 fold ( P < 0.05) and 1.6 fold ( P < 0.05), respectively, after SP administration. SP activated phosphorylated-AMPK and inhibited PPARγ protein expression, improved serum oxidative stress and inflammation ( P < 0.05). SP supplementation leads to increased hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and Superoxide dismutase-2 (SOD-2). Furthermore, SP treatment improved HFD-induced intestinal dysbiosis. Lentisphaerae , Firmicutes , Tenericutes and Peptococcus sp., RC9_gut_group sp., and Parabacteroides sp. of the gut microbiota were significantly associated with hepatic steatosis and indicators related to oxidative stress and inflammation. Therefore, SP can mitigate hepatic lipid accumulation by regulating Nrf-2/HO-1 signaling pathways and gut microbiota. This study offers new evidence supporting the use of SP as a prebiotic treatment for NAFLD.
研究领域:
药理学
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肝病学
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营养学
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微生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2023
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）