JOURNAL OF FOOD BIOCHEMISTRY
·
2025
·Vol. 2025
·期 1
·8349248
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IF 4.2
Yuanjie Wu,Yuntian Zhang,Xike Wu,Ziyan Zhang,Junhui Shen,Nan Tian,Chunlei Fan
This study investigated the effects of tanshinone IIA combined with rutin and squalene (RTS) on atherosclerosis (AS) associated with hyperlipidemia and the underlying mechanisms. Female New Zealand rabbits were subjected to a hyperlipidemia and AS model. Treatment with RTS for 4 weeks reduced the weight, and some serum lipid levels include serum TC, serum TG, serum LDL-C. RTS also improved lesions of the liver and aorta. In vitro analyses showed that RTS significantly activated LDLR-mediated hepatic lipid endocytosis, but blocking LDLR activation with si-SREBP2 attenuated the therapeutic effect, which demonstrated that RTS can activate the SREBP2/LDLR pathway mediating liver clearance of blood lipids. This study highlights the therapeutic potential of RTS in hyperlipidemia and AS. As a convenient form of a combination drug, RTS has shown considerable potential in the improvement of hyperlipidemia combined with AS.
研究领域:
药理学
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心血管病学
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分子生物学
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产品关联
DOI
高影响因子
BIOCHIMIE
·
2023
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IF 3.9
Ya-nan Ou-Yang,Fen-fen Deng,Yun-jia Wang,Meng Chen,Peng-fei Yang,Zhe Yang,Zhongmin Tian
A high-salt diet is known to increase serum cholesterol levels; however, the underlying mechanism of salt - induced dyslipidemia in patients with salt-sensitivity remains poorly understood. We aimed to investigate whether high-salt diet (HSD) can induce dyslipidemia and elucidate the underlying mechanism of salt-induced dyslipidemia in Dahl salt - sensitive (SS) rats. Metabolomic and biochemical analyses revealed that the consumption of an HSD (8 % NaCl) significantly increased the serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL - C) in SS rats. The enzyme-linked immunosorbent assay demonstrated an increase in circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels, accompanied by a decrease in hepatic low-density lipoprotein receptor (LDLR) levels due to HSD consumption. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis revealed that HSD consumption activated sterol regulatory element-binding protein-2 (SREBP2) expression in the liver and kidney, resulting in upregulation of PCSK9 at the transcriptional level in the liver and at the translational level in the kidney, ultimately increasing circulating PCSK9 levels. The combined effects of HSD on the liver and kidney contributed to the development of hypercholesterolemia. Furthermore, an in vitro assay confirmed that high-salt exposure led to an increase in the protein expression of SREBP2 and PCSK9 secretion, thereby reducing low-density lipoprotein (LDL) uptake. This study, for the first time, shows that an HSD induces dyslipidemia through activation of the SREBP2/PCSK9 pathway, providing new insights into the prevention and treatment of dyslipidemia in patients with salt sensitivity.
研究领域:
营养学
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心血管疾病
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分子生物学
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代谢组学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 29
·期 3
·1-12
·
IF 3.4
Mi-Hua Liu,Xiao-Long Lin,Le-Le Xiao
Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS‑CoV‑2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). The expression levels of SARS‑CoV‑2 N protein, SREBP cleavage‑activating protein (SCAP), mature N‑terminal SREBP2, NLRP3, procaspase‑1, cleaved caspase‑1, IL‑1β and IL‑18 were examined by western blotting. The expression levels of SREBP2, HMG‑CoA reductase, HMGCS1, low density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), SREBP1c, fatty acid synthase, stearyl coenzyme A desaturase 1, acetyl‑CoA carboxylase α and ATP‑citrate lyase were determined by reverse transcription‑quantitative PCR. The translocation of SCAP or NLRP3 from the endoplasmic reticulum to the Golgi was detected by confocal microscopy. The results showed that excess PI promoted SCAP‑SREBP and NLRP3 complex translocation to the Golgi, potentially leading to NLRP3 inflammasome activation and lipogenic gene expression. Furthermore, PI amplified SARS‑CoV‑2 N protein‑induced inflammation via the SCAP‑SREBP pathway, which facilitates NLRP3 inflammasome assembly and activation. Inhibition of phosphate uptake with phosphonoformate sodium alleviated NLRP3 inflammasome activation and reduced SREBP‑mediated lipogenic gene expression in VSMCs stimulated with PI and with SARS‑CoV‑2 N protein overexpression. Inhibition of SREBP2 or small interfering RNA‑induced silencing of SREBP2 effectively suppressed the effect of PI and SARS‑CoV‑2 N protein on NLRP3 inflammasome activation and lipogenic gene expression. In conclusion, the present study identified that PI amplified SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation and lipogenic gene expression via the SCAP‑SREBP signaling pathway.
研究领域:
心血管疾病
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传染病
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Yan Shi,Shang Wang,Kai Wang,Ronghua Yang,Dewu Liu,Huaiwei Liao,Yuhan Qi,Keqing Qiu,Yanghong Hu,Huicai Wen,Kui Xu
Macrophage dysfunction is one of the primary factors leading to the delayed healing of diabetic wounds. Hypoxic bone marrow mesenchymal stem cells-derived exosomes (hyBMSC-Exos) have been shown to play an active role in regulating cellular function through the carried microRNAs. However, the administration of hyBMSC-Exos alone in diabetic wounds usually brings little effect, because the exosomes are inherently unstable and have a short retention time at the wounds. In this study, a multifunctional hydrogel based on gallic acid (GA) conjugated chitosan (Chi-GA) and partially oxidized hyaluronic acid (OHA) is prepared for sustained release of hyBMSC-Exos. The hydrogel not only exhibits needs-satisfying physicochemical properties, but also displays outstanding biological performances such as low hemolysis rate, strong antibacterial capacity, great antioxidant ability, and excellent biocompatibility. It has the ability to boost the stability of hyBMSC-Exos, leading to a continuous and gradual release of the exosomes at wound locations, ultimately enhancing the exosomes’ uptake efficiency by target cells. Most importantly, hyBMSC-Exos loaded hydrogel shows an excellent ability to promote diabetic wound healing by regulating macrophage polarization toward M2 phenotype. This may be because exosomal miR-4645-5p and antioxidant property of the hydrogel synergistically inhibit SREBP2 activity in macrophages. This study presents a productive approach for managing diabetic wounds.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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干细胞生物学
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2025
·Vol. 43
·期 11
·e70141
·
IF 2.7
Qianyu Tang,Wenjing Peng,Xiaohua Jiang,Yang Hu,Linxi Chen,Nian Fu
SENP3, a member of the sentrin-specific protease family, plays a pivotal role in lipid metabolism and the pathogenesis of fatty liver disease by regulating the dynamic process of SUMOylation. It has previously been demonstrated that SREBP2 is SUMOylated. However, the function and regulatory mechanism of SENP3-mediated SREBP2 de-SUMOylation in hepatocyte steatosis is unclear. Bioinformatic analysis (proteomes from whole cell extract and nuclear extraction, integrated transcriptomes, RNA sequence) SENP3-driven SREBP2 de-SUMOylation in lipid metabolism; Oil red O, nuclear and cytoplasmic extraction, western blot and immunofluorescence suggest SENP3 vitally contributes to hepatocyte steatosis; NLS predictions, CO-IP, co-transfection of plasmids, confocal microscopy indicates nuclear SENP3 associates with SREBP2 to promote its nuclear translocation; molecular docking and mutation assay confirmed SENP3 is responsible for de-SUMOylation SREBP2 at R576. Treatment with OA increased the level of both SENP3 and its nuclear fraction in HepG2 cells. Interfering with the SUMOylation and deSUMOylation cycle induced hepatocyte steatosis by overexpressing SENP3 and using a SUMO inhibitor, GA. Mechanistically, it is observed that the co-localization between SREBP2 and SENP3 is increased. SENP3 is responsible for de-SUMOylation SREBP2 at R576. Moreover, SENP3-mediated de-SUMOylation may also decrease ZMIZ1-ligated SUMO3 binding to SREBP2 at K464 in the nucleus. RNA interference of SREBP2 cannot reverse SENP3-overexpressed cell steatosis under fatty acid treatment. Expression of SREBP2 in vitro could upregulate the nuclear locations of CCTα binding to DNA without altering the active forms. Our findings demonstrate that de-SUMOylation is an important regulatory mechanism that governs the lipid accumulation of SREBP2 in mammalian cells. Also, the critical role of the de-SUMOylation of SREBP2 by SENP3 to exacerbate steatosis may be a potential therapeutic target for metabolic diseases like MAFLD/MASH. Summary Previous studies have reported SUMOylation of SREBP2, and our published works have centered on SUMOylation of nuclear proteins and hepatocyte metabolism. However, why the K464R mutation completely abolishes SUMO3 modification of SREBP2 remains unsolved. SENP3 de-SUMOylated SREBP2 at R576 to promote its nuclear translocation by de-SUMOylation of SREBP2. This site also influences CCT association with the nuclear envelope and DNA. Building on this, we have filled these gaps and extended the field by demonstrating that SREBP2 recruits CCT dimers to DNA without altering the nuclear size. Our goal is to elucidate the nuclear regulatory mechanisms of metabolic enzymes, providing insights for precision targeting and clinical translation of metabolic diseases like MAFLD.
研究领域:
分子生物学
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细胞生物学
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代谢性疾病
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肝脏病学
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翻译后修饰
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产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2026
·Vol. 22
·期 10
·5301
·
IF 11.7
Xue Li,Min-Yue Yin,Yan-Fei Wei,Jie Xing,Qian Zhang,Ye Zong,Shu-Tian Zhang,Si-An Xie
Dysregulated cholesterol metabolism is a recognized metabolic hallmark of cancer. While the transcription factor SREBP2 is a master regulator of this pathway, how its activation converts metabolic stress into the development of carcinogenic signals in colorectal cancer (CRC) remains unclear. Through clinical and preclinical analyses, we first confirmed that hypercholesterolemia and elevated tumoral SREBP2 are hallmarks of CRC. Using multi-omics integration, we identified CNPY3 as a direct transcriptional target of SREBP2. Functionally, CNPY3 drives CRC cell proliferation, invasion, and tumor growth via a cholesterol synthesis-independent oncogenic program. Clinically, high CNPY3 expression robustly correlated with advanced disease and poor patient survival. Mechanistically, we discovered that CNPY3 undergoes liquid-liquid phase separation (LLPS), a property dependent on its intrinsically disordered C-terminal region. This LLPS capacity is essential for its oncogenic function, as it enables CNPY3 to enhance MDM2 phosphorylation at the activating Ser166 site and promote its nuclear translocation. Consequently, CNPY3 potentiates MDM2-mediated ubiquitination and degradation of the tumor suppressor p53. Genetic ablation of p53 completely abolished the pro-tumorigenic effects of CNPY3, confirming p53 as the critical downstream effector. Crucially, this axis specifically targets wild-type p53, having no effect on common p53 mutants. Pharmacological disruption of the MDM2-p53 interaction with Nutlin-3 effectively reversed CNPY3-driven malignancy both in vitro and in vivo . Our work unveils a SREBP2-CNPY3-MDM2-p53 signaling axis that links cholesterol metabolic dysregulation to p53 pathway inactivation in CRC. We further established that the oncogenic activity of CNPY3 is mediated through its biophysical property of LLPS. These findings nominate CNPY3 as a novel prognostic biomarker and a compelling therapeutic target for p53-wild-type CRC.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Ranyi Luo,Yinhao Zhang,Hong Wang,Bing Xu,Jiaorong Qu,Shuwen Duan,Runping Liu,Jia Liu,Shuo Li,Xiaojiaoyang Li
Ethnopharmacological relevance Hepatic ischemia/reperfusion injury (HIRI) is a common occurrence during or after liver surgery, representing a major cause for postoperative complications or increased morbidity and mortality in liver diseases. Rehmanniae Radix Praeparata (RRP) is a traditional Chinese medicine frequently used and has garnered extensive attention for its therapeutic potential treating cardiovascular and hepatic ailments. Recent studies have indicated the possibility of RRP in regulating lipid accumulation and apoptosis in hepatocytes. Aim of the study This study aimed to investigate the specific mechanisms by which RRP may impede the progression of HIRI through the regulation of lipid metabolism. Materials and methods High-performance liquid chromatography (HPLC) was used to identify the major components of RRP water extract. C57BL/6J mice were orally given RRP at doses of 2.5 g/kg, 5 g/kg, and 10 g/kg for a duration of 7 days before undergoing HIRI surgery. Furthermore, we established a lipid-loaded in vitro model by exposing hepatocytes to oleic acid and palmitic acid (OAPA). The anti-HIRI effect of RRP was determined through transcriptomics and various molecular biology experiments. Results After identifying active ingredients in RRP, we observed that RRP exerted lipid-lowering and hepatoprotective effects on HIRI mice and OAPA-treated hepatocytes. RRP activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR), which further on the one hand, inhibited the cleavage and activation of sterol regulatory element binding protein 2 (SREBP2) by limiting the movement of SREBPs cleavage-activating protein (SCAP)-SREBP2 complex with the help of endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) and insulin-induced gene 1 (INSIG1), and on the other hand, promoted liver X receptor α (LXRα) nuclear transportation and subsequent cholesterol efflux. Meanwhile, the anti-lipotoxic effect of RRP can be partly reversed by an LXRα inhibitor but largely blocked by the application of compound C, an AMPK inhibitor. Conclusion Our study elucidated that RRP served as a potential AMPK activator to alleviate HIRI by blocking SREBP2 activation and cholesterol synthesis, while also activating LXRα to facilitate cholesterol efflux. These findings shed new light on the potential therapeutic use of RRP for improving HIRI.
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jingyi Ren,Jinshi Zuo,Bowen Yin,Dan Huang,Rui Wen,Huanting Pei,Jiarui Liu,Yadong Zhang,Siqi Zhu,Shuman Zhen,Yuxia Ma
Perfluorooctanesulfonate (PFOS) is a widespread, persistent environmental pollutant that exerts apparent liver toxicity. Flaxseed oil (FO), a dietary oil rich in α-linolenic acid, has been demonstrated to possess a diverse array of health benefits. However, whether FO protects against PFOS-induced liver injury and its underlying mechanisms remain unclear. C57/BL6 mice were orally treated with different concentrations of FO alone or in combination with 10 mg/kg of PFOS for 28 consecutive days. Blood and liver tissues were collected for proteomic, histopathological, biochemical, immunohistochemical, and molecular examinations. Results demonstrated that FO supplementation reduced PFOS-induced liver injury, as evidenced by a decrease in histopathological changes, serum transaminase (ALT and AST) levels, levels of oxidative stress, and inflammatory cytokine (TNF-α, IL-1β, and IL-6) levels. Proteomic analyses showed that differentially expressed proteins were enriched in cholesterol metabolic pathways when comparing the PFOS group to the FO supplementation groups. The expression of cholesterol metabolism-related proteins was also subsequently measured, revealing that FO supplementation decreased the protein expressions of SREBP2, HMGCR, and LDLR while increasing the expression of CYP7A1. This study demonstrates that FO can alleviate PFOS-induced hepatotoxicity by regulating hepatic cholesterol metabolism, indicating that FO may serve as an effective dietary intervention for preventing liver injury caused by PFOS.
研究领域:
毒理学
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营养学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Chao Meng,Lingye Zhou,Lin Huang,Qi Gu,Xinyue Du,Cheng Wang,Fanglan Liu,Chunhua Xia
Background Hypercholesterolemia is widely implicated in the etiology of coronary heart disease , stroke, and dementia. Evidence suggests that chlorogenic acid (CA) reduces the risk of cardiovascular disease. Purpose The current study aims to explore the underlying molecular mechanism of CA in lowering cholesterol based on pregnane X receptor (PXR) and sterol regulatory element-binding protein 2 (SREBP2) regulatory pathways and their interactions with heat shock protein 90 (HSP90). Methods A hypercholesterolemic mouse model, HepG2 and Caco2 cell models, metabolomics analysis, and co-immunoprecipitation (COIP) were used to study the mechanism of CA lowering cholesterol. Results Treatment of the hypercholesterolemic mice with CA for 12 weeks significantly reduced body weight, blood lipid, hepatic lipid accumulation , and increased lipid excretion. The nuclear aggregation of PXR and SREBP2 was inhibited simultaneously. In addition, the expression of downstream target genes, including Niemann-pick C1-like 1 (NPC1L1) and 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR), was downregulated after CA administration. Furthermore, in HepG2 and Caco2 cell models, CA reduced intracellular cholesterol levels by inhibiting the nuclear translocation of PXR and SREBP2 and the expression of NPC1L1 and HMGCR. SREBP2 interacts with PXR through HSP90, and CA reduces the binding stability of SREBP2 and HSP90 and enhances the binding of PXR and HSP90, thus reducing the nuclear accumulation of SREBP2 and PXR simultaneously. Moreover, CA promoted the phosphorylation of AMP-activated protein kinase (AMPK) and its binding to SREBP2. This was not conducive to the binding of HSP90 and SREBP2 but enhanced the binding of HSP90 and PXR, thereby inhibiting the nuclear translocation of SREBP2 and PXR and reducing intracellular cholesterol levels. However, no noticeable direct binding between AMPK and PXR was observed. Conclusion CA downregulates NPC1L1 and HMGCR expression by acting on the AMPK/SREBP2 direct pathway and the AMPK/SREBP2/HSP90/PXR indirect pathway, thus retaining cholesterol homeostasis.
研究领域:
药理学
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分子生物学
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心血管疾病
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Mingzhi Wu,Xiaojun Zhou,Xinyi Zhou,Genxin Wang,Yiqun Zeng,Jun Li,Edward V. Prochownik,Fubing Wang,Youjun Li
Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol metabolism is dysregulated is not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell cholesterol biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation by ZDHHC3 at C264 antagonizes HACE1-mediated SCAP ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates ZDHHC3 to form a positive feedback loop, which explains why negative feedback regulation of SCAP/SREBP2 signaling fails in HCC. Increased cholesterol in the tumor microenvironment (TME) restrains CD4 + T cell cytotoxicity. Hence, the cholesterol metabolism reprogramming and cholesterol level alternation in the TME cooperate to promote HCC development. We identified a small-molecule inhibitor of ZDHHC3 that, combined with anti-PD-1 immunotherapy, inhibited diethyl nitrosamine (DEN)/CCl 4 -induced HCC growth in mice. ZDHHC3-mediated SCAP S-acylation reprograms cholesterol metabolism and promotes HCC immune escape. ZDHHC3 is thus identified as a rational chemotherapy target for HCC.
研究领域:
癌症生物学
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分子生物学
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免疫学
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代谢学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Ting Dai,Wenming He,Shuangshuang Tu,Jinru Han,Bo Yuan,Chenyang Yao,Wenzhi Ren,Aiguo Wu
Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO 2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO 2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.
研究领域:
纳米技术
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光疗
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心血管疾病
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脂质代谢
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细胞生物学
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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
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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）