CHINESE MEDICAL JOURNAL
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2025
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IF 7.3
Jia Pengyu,Wang Kui,Cheng Yiqin,Zhang Yan,Lu Yuying,Sun Haodong,Zhang Shuyue,Fan Pei,Zhang Yuanyuan,Yang Liufei,Wang Ning,Lu Haixia,Chen Xinlin,Liu Yong,Wei Haidong,Zhang Pengbo
Plain Language Summary Background: Sevoflurane impairs neurogenesis and cognitive function in the developing brain; however, the underlying mechanisms remain unclear. This study aimed to investigate the role of fatty acid β-oxidation (FAO) in neural stem/progenitor cells (NSPCs) as a potential factor in sevoflurane-induced neurogenesis inhibition and cognitive deficits. Methods: NSPCs, NE-4C cells, and postnatal day 7 (PND 7) rats were exposed to sevoflurane. Cell viability was measured using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Neurogenesis was assessed by immunohistochemistry. Apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Cognitive function was tested with the Morris water maze. Lipid metabolism profiles were analyzed through lipidomics. Message RNA (mRNA) expression levels of key FAO enzymes and the major carnitine transporter were quantified by real-time reverse transcription polymerase chain reaction (RT-qPCR). Protein expression of carnitine palmitoyltransferase 1a (CPT1a) and nuclear peroxisome proliferator-activated receptor α (PPARα) was examined by Western blotting. CPT1a enzymatic activity was determined using a biochemical assay. FAO activity was measured with the FAOBlue assay. Results: Sevoflurane exposure impaired neurogenesis and cognitive function. In NSPCs, sevoflurane exposure induced extensive alterations in lipid metabolism intermediates, inhibited the mRNA expression of acyl-CoA oxidase 1 ( ACOX1 ), acyl-CoA oxidase 3 ( ACOX3 ), hydroxyacyl-CoA dehydrogenase beta subunit ( HADHB ), CPT1a , carnitine palmitoyltransferase 2 ( CPT2 ), acyl-CoA dehydrogenase short-chain ( ACADS ), and solute carrier family 22 member 5 ( SLC22A5 ), suppressed FAO activity, reduced CPT1a expression and activity, and decreased PPARα levels in the nucleus. Enhancing FAO activity in NSPCs ameliorated the negative effects of sevoflurane on neurogenesis. Overexpression of CPT1a rescued the sevoflurane-induced inhibition of FAO activity and neurogenesis in NE-4C cells. Pretreatment with palmitoylethanolamide (PEA), a PPAPα agonist, increased both the nuclear content of PPARα protein and the expression of CPT1a in NSPCs and rat hippocampus after sevoflurane exposure. Furthermore, pretreatment with PEA or the CPT1a substrate carnitine rescued sevoflurane-induced damage to FAO activity in NSPCs, neurogenesis, and cognitive function. Conclusion: Sevoflurane impairs neurogenesis and cognitive function by suppressing FAO in NSPCs of the developing brain. Boosting FAO activity in NSPCs could be a potential strategy to prevent sevoflurane-induced cognitive deficits. Plain Language Summary This study explored how sevoflurane, an anesthetic, affects brain development by impairing neurogenesis and cognitive function. Researchers found that sevoflurane disrupts fatty acid β-oxidation (FAO) in neural stem/progenitor cells (NSPCs), leading to changes in lipid metabolism and reduced expression of key enzymes. Enhancing FAO activity, either by overexpressing certain proteins or using compounds like palmitoylethanolamide (PEA) and carnitine, helped mitigate these negative effects. This suggests that targeting FAO in NSPCs could be a promising approach to counteract sevoflurane-induced cognitive deficits in the developing brain. Text is machine generated and may contain inaccuracies. FAQ
研究领域:
神经科学
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发育生物学
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麻醉学
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代谢学
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干细胞研究
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DOI
高影响因子
LIFE SCIENCES
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2021
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IF 5.037
Yue Xiong,Yan Chen,Xinping Huang,Zhen Yang,Jiaye Zhang,Xiaorui Yu,Ji Fang,Jiawang Tao,Kai You,Ziqi Cheng,Shenglin Tan,Yingying Xu,Fang Yuan,Ying Liu,Yuanqi Zhuang,Fan Yang,Yinxiong Li
Aim This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms. Main methods Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo. Results In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid β-oxidation through elevated expression of peroxisome proliferator-activated receptor α (PPARα). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3β), leading to the improvement of insulin resistance. Significance ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis.
研究领域:
药理学
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代谢学
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肝病学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2020
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IF 2.985
Peng Ma,Rongrong Huang,Jingyao Jiang,Yuan Ding,Tingting Li,Yu Ou
C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα , which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36 , IL6 and TNFα . These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.
研究领域:
药理学
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肝病学
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营养保健品
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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 AGRICULTURAL AND FOOD CHEMISTRY
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2020
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IF 4.192
Niu Zhang,Jun-Peng Zeng,Yan-Ping Wu,Meng Wei,Hong Zhang,Liufeng Zheng,Ze-Yuan Deng,Jing Li
The digestion and absorption of different structural lipids in human milk may be different. Hence, by simulating in vitro infant digestion and Caco-2 cells to explore the effects of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL)/1,3-dilinoleoyl-2-palmitoylglycerol (LPL)/1,3-dioleoyl-2-palmitoylglycerol (OPO) and their mixtures (M) (OPL/LPL/OPO in M1, M2, and M3 were 1.5/0.5/1, 1.2/1.2/1, and 0.5/0.2/1, respectively) on digestion and absorption. The digestibility of the OPO group was higher than those of the OPL and LPL groups, and the M3 group was higher than the M1 and M2 groups. The synthesis and transport of triglycerides in Caco-2 cells in OPL and LPL groups were higher than the OPO group, and the M1 group was significantly higher than that of M3. The expression of FABP1, PPARα, and MTT protein in OPL and M1 groups was significantly higher than OPO and M3, respectively. There are differences in the digestion and absorption of differently structured lipids from this study.
研究领域:
营养学
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生物化学
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儿科
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Dong-xuan Zheng,Qiang Hou,Tao-tao Xue,Xiang Gao,Ruo-yu Geng,Li-mei Wen,Zhi Wang,Qiang Yin,Hai-long Yin,Jun-ping Hu,Jian-hua Yang
Ethnopharmacological relevance Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. Objective The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. Methods The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro . In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo . Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. Results This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p–NF–κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. Conclusions YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.
研究领域:
药理学
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代谢组学
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分子生物学
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民族药理学
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肝病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
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2021
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IF 4.698
Xixi Song,Minghui Wang,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Hai Lin
Ghrelin, classically known as a central appetite-stimulating hormone, has recently been recognized to play an important role in peripheral tissue energy metabolism. In chicken, contrary to mammal, ghrelin acts as an anorexia signal, increased by fasting and further elevated after refed. In the present study, the effect of ghrelin on glucose/lipid utilization by peripheral tissues was investigated. Injection of exogenous acyl ghrelin reduced plasma triglyceride and glucose levels of chickens at both fasting and fed status. In the in vitro cultured chicken primary hepatocytes, adipocytes, and myoblasts, ghrelin suppressed glucose uptake , stimulated fatty acids uptake and oxidation , and decreased TG content. In hepatocyte, ghrelin increased the activities of LPL and HL, and upregulated the expression levels of gene ACC , CPT1 , and PPARα . Ghrelin treatment markedly increased the protein level of p-ACC, PPARγ, PGC1α, and CPT1 in hepatocytes, adipocytes and myoblasts. Inhibition of AMPK activity by Compound C had no influence on glucose uptake by hepatocyte, adipocyte, and myoblast, but further amplified the stimulated fatty acid uptake of adipocyte by ghrelin. The present result demonstrates that ghrelin facilitates the uptake and oxidation of fatty acid and cut down the utilization of glucose by the liver, muscle, and adipose tissues. The result suggests that ghrelin functions as a signal of fatty acid oxidation. The study provides a vital framework for understanding the intrinsic role of ghrelin as a crucial factor in the concerted regulation of metabolic substrate of hepatocytes, adipocytes, and myoblasts.
研究领域:
内分泌学
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代谢
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动物生理学
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产品关联
DOI
PubMed
高影响因子
NUTRITION RESEARCH
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2019
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IF 2.627
Jia Wang,Tian Gao,Feng Wang,Jie Xue,Hua Ye,Meilin Xie
Luteolin , a natural flavonoid , can attenuate hepatic lipid accumulation and insulin resistance in obese mice . Therefore, we hypothesized that luteolin may also improve the abnormal glucolipid metabolism of hypertrophic myocardial cells. This study aimed to investigate the effect and possible molecular mechanisms of luteolin. Hypertrophic H9c2 cells were induced by angiotensin II/hypoxia and simultaneously treated with 2 to 8 μg/mL luteolin for 24 h. Luteolin might dose-dependently decrease intracellular total protein, atrial natriuretic peptide , and free fatty acid levels , and increase supernatant glucose levels . Western blot assay showed that luteolin could inhibit the expressions of intracellular hypoxia inducible factor-1α (HIF-1α) and glucose transporter-4 (GLUT-4) proteins, and increase the expressions of intracellular peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1A (CPT-1A), and pyruvate dehydrogenase kinase-4 (PDK-4) proteins. These findings demonstrate that luteolin can improve abnormal glucolipid metabolism in angiotensin II/hypoxia-induced hypertrophic H9c2 cells, and its mechanisms are related to the inhibition of HIF-1α expression and subsequent modulation of PPARα-mediated target genes, including CPT-1A, PDK-4, and GLUT-4.
研究领域:
药理学
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心脏病学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2018
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IF 3.831
Jiao Shihong,Tang Binghua,Wang Yong,Li Chun,Zeng Zifan,Cui Lixia,Zhang Xuefeng,Shao Mingyan,Guo Dongqing,Wang Qiyan
Coronary artery disease (CAD) is one of the leading causes of deaths worldwide. Energy metabolism disorders, including a reduction in fatty acids oxidation and upregulation of glycolysis pathway, are involved in the process of CAD. Therapeutic angiogenesis has become a promising treatment for CAD. Traditional Chinese medicines, such as Danqi Pill (DQP), have been proven to be effective in treating CAD in China for many years. However, the pro-angiogenic effects of DQP based on fatty acids oxidation are still unknown and the mechanism is worthy of investigation. In this study, left anterior descending (LAD) coronary artery was ligated to induce the CAD models in vivo, and cardiac functions were examined using echocardiography. Human umbilical vein endothelial cells (HUVEC) were subjected to H2O2-induced oxidative stress in vitro. The effects of DQP on CAD rat models and in vitro HUVEC were detected. Our results showed that DQP had cardio-protective effects in rat model. The intensity of capillaries in the marginal area of infarction of the rat heart was increased remarkably in DQP group, and the expression of PPARα and VEGF-2 were increased. The key enzymes involved in the transportation and intake of fatty acids, including CPT1A and CD36, both increased. In H2O2-induced endothelial cells injury models, DQP also showed protective roles and promoted capillary-like tube formation. DQP up-regulated key enzymes in fatty acids oxidation in H2O2-treated HUVEC. In addition, inhibition of CPT1A compromised the pro-angiogenic effects of DQP. In conclusion, fatty acids oxidation axis PPARα-CD36-CPT1A was involved in the pro-angiogenic roles of DQP against CAD. Cardiac CPT1A may serve as a target in therapeutic angiogenesis in clinics.
研究领域:
心脏病学
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药理学
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分子生物学
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中医
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Yuxiang Sun,Fangfang Shi,Yajun Niu,Yu Zhang,Fei Xiong
Lipid deposition induced various diseases including nonalcoholic fatty liver and hyperlipemia. The excessive accumulation of triglyceride (TG) and the deposition of fat were the two most critical causes. Here, we developed Fe 3 O 4 @ [email protected] nanoparticles (NPs) with amphiphilic structures, which exhibited an excellent role in eliminating excess TG. Hydrophobic TG was adsorbed efficiently by Fe 3 O 4 @ [email protected] NPs through the “liposuction effect” and the formation of [email protected] complex was then conducted. The [email protected] complex was further enclosed by the endosome based on the endocytosis and subsequently was taken into the lysosome, degrading with the help of lipases. Meanwhile, the “nano-enzyme effect” of Fe 3 O 4 NPs recovered the lipid-regulated proteins including PPARα, further triggering biodegradation pathways of TG, although the lipid-regulated proteins were obviously inhibited in the high-fat hepatocytes models. These two mechanisms of Fe 3 O 4 @ [email protected] NPs together achieved the down-regulation of TG in vivo and in vitro. Therefore, our findings provided a novel thought in treating these diseases associated with lipid deposition, that is, nanoparticles modified by specific structure exhibit a superior TG removal.
研究领域:
纳米技术
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药理学
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肝病学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
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2026
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IF 5.1
Hong Yang,Peng Zhao,Xiaolei Wei,Chao Huang,Wu-Hong Lv,Yu-Chen Zhou,Zhi Luo
Copper oxide nanoparticles (CuO NPs) are widely used in industry and agriculture, leading to their persistent occurrence and accumulation in aquatic environments and posing potential environmental risks. However, the specific role and underlying mechanisms of CuO NPs on the health risks of aquatic organisms remain unclear. This study revealed that dietary exposure to high levels of CuO NPs elevated hepatic Cu content, induced oxidative stress and mitochondrial dysfunction that exacerbate hepatic lipotoxicity. Mechanistically, high dietary CuO NPs enhanced the interaction between domains 1 and 3 of the Cu chaperone for superoxide dismutase (Ccs) and mitogen-activated protein kinase kinase 1 (Mek1), which subsequently activated the phosphorylation of extracellular signal-regulated protein kinase 1/2 (Erk1T202/Y204 and Erk2T185/Y187). The activated Erk1/2 mediated CuO NPs-induced lipotoxicity by suppressing the expression of peroxisome proliferator-activated receptor α (Pparα) and promoting its phosphorylation at the S77 site. Further investigation demonstrated that Pparα phosphorylation impaired fatty acid β-oxidation by downregulating the promoter activities of long chain acyl-coA dehydrogenase (acadl) and carnitine palmitoyl transferase Ia1b (cptIa1b). For the first time, this study elucidated the novel mechanism by which CuO NPs induced metabolic disorder via the Ccs/Mek1/Erk1/2/Pparα signaling axis. These findings provide critical evidence for the toxicological and environmental risk assessment of nanoparticles, while also deepen the mechanistic understanding of nanometal exposure-induced health effects in aquatic animals within complex environments.
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Qingqing Yu,Yayun Liu,Yufei Wu,Yong Chen
Aims Curcumin is a polyphenol compound with many pharmacological activities including antioxidant, lipid-loweing and liver protective. Dihydrocurcumin (DHC) is one of the major metabolites of curcumin. So far, the pharmacological activity of DHC has not been reported. Here, we evaluate the effects of DHC on oleic acid (OA)-induced lipid accumulation, oxidative stress and insulin resistance and the underlying mechanism in L02 and HepG2 cells. Main methods OA-induced L02 and HepG2 cells were used as the in vitro model of nonalcoholic fatty liver disease (NAFLD). Lipid accumulation, oxidative stress, glucose uptake and cell inflammation were evaluated by cellular biochemical assay, respectively. Signaling pathways involved in lipid metabolism including peroxisome proliferator activated receptor-α (PPARα), the sterol regulatory element binding protein-1C (SREBP-1C) and patatin-like phospholipase domain containing 3 (PNPLA3), glucose uptake including phosphatidylinositol 3-kinase (PI3K) and phosphorylated serine-threonine protein kinase (pAKT), and oxidative stress including nuclear factor E2-related factor 2 (Nrf2), cytochrome P450 4A (CYP4A) and 2E1 (CYP2E1) were investigated by western blotting and RT-qPCR, respectively. Key findings DHC decreased the levels of cellular triglycerides (TG) by regulating the mRNA and protein expression levels of SREBP-1C , PNPLA3 and PPARα . At the same time, DHC improved the hepatocellular glucose uptake by increasing the protein expression levels of pAKT and PI3K. Furthermore, DHC reduced the levels of cellular NO and ROS via Nrf2 signaling pathways. Significance The present study firstly revealed that DHC ameliorated OA-induced steatosis through regulating the lipid metabolism, oxidative stress and insulin resistance in HepG2 and L02 cells.
研究领域:
药理学
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细胞生物学
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代谢
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肝脏疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
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2017
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IF 1.916
Xin Yang,Qian Wang,Zeng-run Pang,Meng-ran Pan,Wen Zhang
Context: Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited.Objective: We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved.Materials and methods: C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism.Results: FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01–47.70%).Conclusion: This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.
研究领域:
药理学
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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