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DCA
Animal Nutrition · 2022 · IF 5.285

Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity

Yuan Luo,Wenhao Zhou,Ruixin Li,Samwel M. Limbu,Fang Qiao,Liqiao Chen,Meiling Zhang,Zhen-Yu Du

Pyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis plays an important role in regulating glucose metabolism in mammals. However, the regulatory function of PDKs-PDHE1α axis in the glucose metabolism of fish is not well known. This study determined whether PDKs inhibition could enhance PDHE1α activity, and improve glucose catabolism in fish. Nile tilapia fingerlings (1.90 ± 0.11 g) were randomly divided into 4 treatments in triplicate (30 fish each) and fed control diet without dichloroacetate (DCA) (38% protein, 7% lipid and 45% corn starch) and the control diet supplemented with DCA, which inhibits PDKs through binding the allosteric sites, at 3.75 (DCA3.75), 7.50 (DCA7.50) and 11.25 g/kg (DCA11.25), for 6 wk. The results showed that DCA3.75, DCA7.50 and DCA11.25 significantly increased weight gain, carcass ratio and protein efficiency ratio ( P  < 0.05) and reduced feed efficiency ( P  < 0.05) of Nile tilapia. To investigate the effects of DCA on growth performance of Nile tilapia, we selected the lowest dose DCA3.75 for subsequent analysis. Nile tilapia fed on DCA3.75 significantly reduced the mesenteric fat index, serum and liver triglyceride concentration and total lipid content in whole fish, and down-regulated the expressions of genes related to lipogenesis ( P  < 0.05) compared to the control. The DCA3.75 treatment significantly improved glucose oxidative catabolism and glycogen synthesis in the liver, but significantly reduced the conversion of glucose to lipid ( P  < 0.05). Furthermore, the DCA3.75 treatment significantly decreased the PDK2/4 gene and protein expressions ( P  < 0.05), accordingly stimulated PDHE1α activity by decreasing the phosphorylated PDHE1α protein level. In addition, DCA3.75 treatment significantly increased the phosphorylated levels of key proteins involved in insulin signaling pathway and glycogen synthase kinase 3β ( P  < 0.05). Taken together, the present study demonstrates that PDK2/4 inhibition by using DCA promotes glucose utilization in Nile tilapia by activating PDHE1α and improving insulin sensitivity. Our study helps to understand the regulatory mechanism of glucose metabolism for improving dietary carbohydrate utilization in farmed fish.

CAS / MDL: 13425-80-4
研究领域: 水产养殖 · 代谢 · 营养 · 分子生物学
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2021 · IF 3.764

Impregnation of 1-n-Butyl-3-methylimidazolium Dicyanide [BMIM][DCA] into ZIF-8 as a Versatile Sorbent for Efficient and Selective Separation of CO2

Shahid Hussain,Haifeng Dong,Yanqiang Zhang,Guoxiong Zhan,Shaojuan Zeng,Huifang Duan,Xiangping Zhang

The efficient capture of carbon dioxide (CO2) has industrial, economic, and environmental significance. Here, CO2 capture performance in terms of CO2/CH4 selectivity for the zeolitic imidazolate framework (ZIF-8) is enhanced by impregnation of 1-n-butyl-3-methylimidazolium dicyanide [BMIM][DCA]. The preparation of ionic liquids (ILs)/ZIF-8 composites, their comprehensive characterization, and the impact of IL impregnation are all investigated. The crystal structure and morphology of ZIF-8 remained intact even after the impregnation of ILs, according to X-ray diffraction and scanning electron microscopy studies. The infrared spectroscopy known as Fourier transform infrared spectroscopy determines the interaction between ILs and ZIF-8 in the composite. The isotherm fitting was also performed by dual site Langmuir models, which showed good agreement with the experimental results. The CO2/CH4 selectivity results demonstrated that the ideal selectivity for the IL-impregnated ZIF-8 composite has five times higher selectivity than pristine ZIF-8 at 0.05 bar which is the highest reported selectivity. The normalized selectivity of this type of IL/ZIF-8 composite is also higher. This study suggested that the IL/MOF composite with a tunable structure have a strong potential for enhanced acid gas separation performance to meet the environmental challenges.

研究领域: 材料科学 · 环境科学
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FUEL · 2022 · IF 8.035

An experimental study on the hypergolic process enhanced by pre-ignition heat release: [AMIM][DCA]/furfuryl alcohol blends reacting with white fuming nitric acid

Yingtao Wu,Zhi Wang,Lihan Fei,Yang Guo,Yang Liu,Chenglong Tang,Zuohua Huang

The hypergolic ignition behaviors of [AMIM][DCA] (1-allyl-3-methylimidazolium dicyanamide)/furfuryl alcohol (FA) blends reacting with white fuming nitric acid (WFNA) are investigated using drop test approach. Morphology results from two high speed cameras and temperature profiles from an infrared camera are combined in analyzing the hypergolic process. A typical hypergolic process observed in this work involves a mixing dominant stage, a stage with moderate temperature rising and vapor/secondary droplets emerging, and a stage with violent temperature rising accompanied by flame occurrence. Two kinds of delay times are used to characterize the hypergolic process which are found to be nonmonotonic with the variations of FA fractions. FA, though not hypergolic with WFNA, exhibits extensive pre-ignition heat release due to its physical and chemical properties, which enhances the hypergolic process of [AMIM][DCA]/FA blends with WFNA.

CAS / MDL: 64-18-6
研究领域: 化学工程 · 航空航天工程 · 燃烧科学
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PROTEOMICS · 2022 ·Vol. 23 ·期 2 ·2200362 · IF 5.393

Proteomic and metabonomic analysis uncovering Enterovirus A71 reprogramming host cell metabolic pathway

Huichun Shi,Siyuan Liu,Zhimi Tan,Lin Yin,Liyan Zeng,Tiefu Liu,Shuye Zhang,Lijun Zhang

Enterovirus A71 (EV71) infection can cause hand, foot, and mouth disease (HFMD) and severe neurological complications in children. However, the biological processes regulated by EV71 remain poorly understood. Herein, proteomics and metabonomics studies were conducted to uncover the mechanism of EV71 infection in rhabdomyosarcoma (RD) cells and identify potential drug targets. Differential expressed proteins from enriched membrane were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics technology. Twenty-six differential proteins with 1.5-fold ( p < 0.05) change were detected, including 14 upregulated proteins and 12 downregulated proteins. The upregulated proteins are mainly involved in metabolic process, especially in the glycolysis pathway. Alpha-enolase (ENO1) protein was found to increase with temporal dependence following EV71 infection. The targeted metabolomics analysis revealed that glucose absorption and glycolysis metabolites were increased after EV71 infection. The glycolysis pathway was inhibited by knocking down ENO1 or the use of a glycolysis inhibitor (dichloroacetic acid [DCA]); and we found that EV71 infection was inhibited by depleting ENO1 or using DCA. Our study indicates that EV71 may reprogram glucose metabolism by activating glycolysis, and EV71 infection can be inhibited by interrupting the glycolysis pathway. ENO1 may be a potential target against EV71, and DCA could act as an inhibitor of EV71.

CAS / MDL: 53411-70-4
研究领域: 病毒学 · 蛋白质组学 · 代谢组学 · 分子生物学 · 细胞生物学 · 传染病学
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Biomaterials Science · 2022 ·Vol. 10 ·期 9 ·2370-2383 · IF 7.59

An enzyme-responsive and NIR-triggered lipid–polymer hybrid nanoplatform for synergistic photothermal/chemo cancer therapy

Lu Tang,Qiaqia Xiao,Yue Yin,Yijun Mei,Jing Li,Lin Xu,Hongbin Gao,Wei Wang

A combination of photothermal therapy (PTT) and chemotherapy is an emerging therapeutic strategy with promising clinical prospects in cancer treatment. Despite the huge progress achieved in the past years, a number of obstacles still hamper the therapeutic efficacy of this synergistic modality such as uneven heat distribution, lack of targetability of anti-cancer agents and dosage-related side effects. Thus, developing a nanoplatform for targeted drug delivery against cancer is of great necessity. Herein, a lipid–polymer hybrid nanosystem (LP/ID) based on polyethyleneimine (PEI)-lecithin-polyethylene glycol (PEG) was fabricated to co-load indocyanine green (ICG) and dichloroacetate (DCA) for combined photothermal/chemotherapy. DCA and ICG were linked to the PEI backbone to form a dense hydrophobic core through amide bonds and electrostatic interactions, which increased the payload of DCA and ICG as well as achieved enzyme-responsive drug release because of the overexpressed amidase in tumor cells. Lecithin and DSPE-PEG2000 self-assembled around the hydrophobic complexes to obtain prolonged blood circulation and attenuated systemic toxicity of the hybrid nanosystem. The prepared LP/ID exhibited favourable stability in a physiological environment, good tumor imaging properties, and satisfactory photothermal/chemotherapeutic performance. Moreover, LP/ID could also enhance the cellular uptake and tumor retention capacity in comparison with free drug administration. Notably, by co-loading two therapeutic agents with different anti-cancer mechanisms, an obvious inhibitory effect on tumor growth was observed with negligible damage to normal tissues and organs because of the synergistic photothermal/chemotherapy effect, indicating the great potential of LP/ID as a robust nanoplatform for cancer treatment.

研究领域: 癌症治疗 · 纳米医学 · 材料科学 · 药剂学
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Gut Microbes · 2025 · IF 11

Dietary cholesterol impairs cognition via gut microbiota-derived deoxycholic acid in obese mice

Yan Liu,Zhangtie Wang,Yansong Zhang,Tian Zhao,Qingjun Zhang,Weisu Huang,Baiyi Lu

Dietary cholesterol is often found in a high-fat diet (HFD) and excessive intake is harmful to cognitive function. The gut microbiome constitutes an environmental factor influenced by diet, which regulates cognitive function via the gut-brain axis. The present study explored the role of dietary cholesterol in HFD-induced cognitive impairment and the participation of the gut microbiota and metabolites. Here, we found that dietary cholesterol promoted cognitive impairment in HFD-fed mice, which was associated with an increase in gut microbiota containing 7α-dehydroxylase, including Lachnospiraceae bacterium, Dorea sp. Clostridium sp. and elevated levels of deoxycholic acid (DCA) in the hippocampus. Upon dietary cholesterol intake, the activity of gut microbiota in mice to produce DCA is increased. Fecal microbiota transplantation confirmed that the cognitive impairment-promoting process was driven by gut microbiota. Reducing circulating bile acid levels with cholestyramine improved cognitive decline in mice, whereas hippocampal administration of DCA worsened cognitive function. Pharmacological inhibition of hippocampal apical sodium bile acid transporter reduces neuronal DCA accumulation and improves neuronal apoptosis as well as cognitive impairments in mice. Overall, this study revealed that dietary cholesterol promotes HFD-induced cognitive impairment by inducing the production of DCA through gut microbiota metabolism.

CAS / MDL: 95975-55-6 50-02-2
研究领域: 神经科学 · 微生物学 · 营养学 · 代谢组学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FISH & SHELLFISH IMMUNOLOGY · 2023 · IF 4.7

PDK inhibition promotes glucose utilization, reduces hepatic lipid deposition, and improves oxidative stress in largemouth bass (Micropterus salmoides) by increasing pyruvate oxidative phosphorylation

An-Hui Jin,Yi-Fan Qian,Jiong Ren,Jin-Gang Wang,Fang Qiao,Mei-Ling Zhang,Zhen-Yu Du,Yuan Luo

In omnivorous fish, the pyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis is essential in the regulation of carbohydrate oxidative catabolism. Among the existing research, the role of the PDKs-PDHE1α axis in carnivorous fish with poor glucose utilization is unclear. In the present study, we determined the effects of PDK inhibition on the liver glycolipid metabolism of largemouth bass ( Micropterus salmoides ). DCA is a PDK-specific inhibitor that inhibits PDK by binding the allosteric sites . A total of 160 juvenile largemouth bass were randomly divided into two groups, with four replicates of 20 fish each, fed a control diet and a control diet supplemented with dichloroacetate (DCA) for 8 weeks. The present results showed that DCA supplementation significantly decreased the hepatosomatic index , triglycerides in liver and serum, and total liver lipids of largemouth bass compared with the control group. In addition, compared with the control group, DCA treatment significantly down-regulated gene expression associated with lipogenesis . Furthermore, DCA supplementation significantly decreased the mRNA expression of pdk3a and increased PDHE1α activity. In addition, DCA supplementation improved glucose oxidative catabolism and pyruvate oxidative phosphorylation (OXPHOS) in the liver, as evidenced by low pyruvate content in the liver and up-regulated expressions of glycolysis-related and TCA cycle/OXPHOS-related genes. Moreover, DCA consumption decreased hepatic malondialdehyde (MDA) content, enhanced the activities of superoxide dismutase (SOD), and increased transforming growth factor beta ( tgf-β ), glutathione S-transferase ( gst ), and superoxide dismutase 1 ( sod1 ) gene expression compared with the control diet. This study demonstrated that inhibition of PDKs by DCA promoted glucose utilization, reduced hepatic lipid deposition, and improved oxidative stress in largemouth bass by increasing pyruvate OXPHOS. Our findings contribute to the understanding of the underlying mechanism of the PDKs-PDHE1α axis in glucose metabolism and improve the utilization of dietary carbohydrates in farmed carnivorous fish.

研究领域: 水产养殖 · 鱼类生理学 · 营养学 · 生物化学 · 分子生物学
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