INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shaoyang Zhi,Junli Wang,Yiran Wang,Yijie Li,Mengjuan Zhao,Liping Yang,Chaobin Qin,Xiao Yan,Guoxing Nie
AMPKα1 and AMPKα2, key kinases in regulating energy homeostasis, have not been previously cloned or characterized in common carp ( Cyprinus carpio ). This study identified the open reading frame (ORF) sequences of ampkα1 (1722 bp, encoding 573 amino acids) and ampkα2 (1659 bp, encoding 552 amino acids) through homologous cloning. Sequence alignment and phylogenetic analysis showed a high similarity of both genes with fish homologs. Expression analysis revealed that ampkα1 and ampkα2 are widely expressed across tissues in carp, with ampkα1 highly expressed in the gonads and ampkα2 in the heart. Fasting significantly reduced ampkα1 expression in the heart, adipose tissue, and foregut but increased it in the hindgut and white muscle. Similarly, ampkα2 expression decreased in the hypothalamus and muscle during fasting, with an increase in the midgut. Glucose tolerance tests showed dynamic regulation of ampkα1 and ampkα2 , with initial downregulation followed by upregulation in the hepatopancreas, red muscle, and brain. High-glucose and high-fat diets significantly increased ampkα1 and ampkα2 expression in multiple tissues. Insulin and glucagon treatment induced time-dependent changes in both genes in hepatocytes, while Aeromonas hydrophila infection, LPS, and Poly (I:C) stimulation upregulated ampkα1 and ampkα2 in immune-related tissues. Knockdown of ampkα2 , but not ampkα1 , reduced glut1b mRNA levels, while both knockdowns of ampkα1 and ampkα2 promoted the expression of gsk3β , pygm , acc , fas , srebp , cs , and pro-inflammatory cytokines, suggesting their involvement in metabolic and immune regulation in carp.
研究领域:
分子生物学
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营养学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2025
·
IF 7.7
Zhe Wang,Mingjun Zhu,Yao Hu,Jiaxi Liu,Xiaoyu Ma,Hong Zhou
The antioxidant 6PPD and its oxidized product 6PPD-Quinone (6PPDQ) have attracted considerable attention due to their various acute toxicities to aquatic organisms. However, the chronic toxicity of two compounds in aquatic animals is still unknown. Here, adult zebrafish were exposed to 6PPD and 6PPDQ at environmentally relevant concentrations (20 μg/L) for 28 days, and histological analysis showed that 6PPD caused more severe hepatic vacuolization than 6PPDQ. Meanwhile, 6PPD induced more serious lipid accumulation and a higher increase in triglyceride and total cholesterol levels than 6PPDQ, suggesting higher hepatotoxicity of 6PPD. Furthermore, transcriptomic analysis revealed that both compounds disturbed glucolipid metabolism to different degrees by altering the expression of different peroxisome proliferator-activated receptors (PPARs), in which 6PPD inhibited gene expressions in glucolipid metabolism possibly by PPARα, PPARβ and RXR, while 6PPDQ disrupted the expressions of partial genes in similar pathways probably via PPARγ. Additionally, 6PPD but not 6PPDQ increased Fe 2+ content, decreased the protein levels of ferroportin 1, ferritin and glutathione peroxidase 4, accompanied with the increase of malondialdehyde level and the decrease of glutathione content, suggesting ferroptotic response by 6PPD. Overall, our data deepened the understanding of 6PPD- and 6PPDQ-induced hepatotoxicity association with glucolipid metabolism disorders and ferroptotic responses.
研究领域:
环境毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
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IF 4.872
Ruifen Kang,Aneela Perveen,Chunmei Li
T-2 toxin is a kind of group A trichothecenes mycotoxins , frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK , Glut2 , Fas , Acox1 , Hmgcr , PPARα , Srebp1 and CD36 . These results demonstrated T-2 toxin exposure to pregnant mice could cause liver glycolipid metabolism disruption in the young mice and the toxic effects weakened on PND 56.
研究领域:
毒理学
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营养学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
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IF 5.6
Shuqi He,Zhiyuan Xu,Jie Li,Yueping Guo,Qianxia Lin,Huoxi Jin
Three oligopeptides of KLHDEEVA (KA-8), LALFVPR (LR-7), and PSRILYG (PG-7) were selected from the hydrolysate of Harpadon nehereus . They significantly improved cell morphology and decreased aspartate aminotransferase (AST), alanine transaminase (ALT), and reactive oxygen species (ROS) levels in high glucose-induced HepG2 cells. LR-7 showed good performance in regulating both antioxidant and glucose metabolism in high glucose-induced HepG2 cells, evidenced by improved expression levels of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase 1 (PEPCK1), heme-oxygenase (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and nuclear factor E2-related factor 2 (Nrf2). PG-7 had better performance in reducing triglyceride (TG) and total cholesterol (TC) levels and enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels. KA-8 showed stronger effects on improving low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), phosphorylation protein kinase B (p-AKT), and phosphorylation glycogen synthase kinase-3 (p-GSK-3β) levels. The results showed that all three peptides could protect against high glucose-induced HepG2 damage through different molecular mechanisms. The protective effects of LR-7 may be attributed mainly to its excellent glycolipid metabolism regulation and oxidative stress attenuation via Nrf2 pathway activation. KA-8 may exert its protective role through AKT/GSK-3β signaling pathway activation.
研究领域:
生物化学
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分子生物学
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医学
✓ 已验证
DOI
高影响因子
Journal of Functional Foods
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2018
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IF 3.47
Du-Xin Jin,Jun-Fang He,Xue-Gang Luo,Tong-Cun Zhang
Hypericum attenuatum Choisy, as an edible medicinal plant, possesses multiple therapeutic effects. Type 2 diabetes is a metabolic disorder that has become a major threat to public health. The objective of this study was to investigate the hypoglycemic effect of Hypericum attenuatum Choisy extracts (HaC) on T2DM mice and modulatory effect of HaC on composition of intestinal microflora. T2DM mice were treated with HaC for 5 weeks. HaC could modulate fasting blood glucose, improve hepatic insulin sensitivity and promote hepatic glycogen storage by activating IRS1/PI3K/AKT pathway. Moreover, HaC regulated dysfunctional lipid metabolism and reduced inflammation in T2DM mice. Additionally, HaC treatment could modulate the compositions of gut microbiota in small intestine and colon with the altered abundances of Firmicutes , Bacteroidetes and Proteobacteria . Meanwhile, HaC treatment could augment short chain fatty acids contents. These results demonstrate that H. attenuatum Choisy may be a potential therapy for the treatment of T2DM.
研究领域:
药理学
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糖尿病研究
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
AQUACULTURE NUTRITION
·
2023
·
IF 3.5
Longwei Xi,Qisheng Lu,Yulong Liu,Yulong Gong,Haokun Liu,Junyan Jin,Zhimin Zhang,Yunxia Yang,Xiaoming Zhu,Dong Han,Shouqi Xie
Excessive carbohydrate intake leads to metabolic disorders in fish. However, few literatures have reported the appropriate carbohydrate level for zebrafish, and the metabolic response to dietary carbohydrate remains largely unknown in zebrafish. This study assessed the responses of zebrafish and zebrafish liver cell line (ZFL) to different carbohydrate levels. In vivo results showed that ≥30% dietary dextrin levels significantly increased the plasma glucose content, activated the expression of hepatic glycolysis-related genes, and inhibited the expression of hepatic gluconeogenesis-related genes in zebrafish. Oil red O staining, triglyceride content, and Hematoxylin-Eosin staining results showed that dietary dextrin levels of ≥30% significantly increased lipid accumulation and liver damage, as well as processes related to glycolipid metabolism and inflammation in zebrafish. In ZFL, the transcription factor sterol regulatory element binding protein-1c signal intensity, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) signal intensity, and triglyceride content were also significantly increased when incubated in high glucose, along with abnormal glycolipid metabolism and increased inflammation-related genes. In conclusion, we demonstrated that the maximum dietary carbohydrate level in adult zebrafish should be less than 30%. Excess dietary carbohydrates (30%–50%) caused hepatic steatosis and damage to zebrafish, similar to that seen in aquaculture species. Thus, this study assessed responses to different carbohydrate levels in zebrafish and illustrated that zebrafish is an optimal model for investigating glucose metabolism in some aquatic animals.
研究领域:
水产动物营养学
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分子生物学
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代谢研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Hu Zhang,Guiling Yang,Zhiwei Bao,Yuanxiang Jin,Jianmei Wang,Jing Chen,Mingrong Qian
Difenoconazole is a commonly used triazole fungicide that consists of four stereoisomers [( 2S,4S )-, ( 2S,4R )-, ( 2R,4R )-, and ( 2R,4S )-isomers] with different bioactivity. For example, the toxicity of the ( 2R,4S )-isomer to fish is approximately seven times higher than that of the ( 2S,4S )-isomer. However, the stereoselective toxic effects of difenoconazole stereoisomers on mammals have received little attention. In the present study, adult male mice were orally treated with a mixture of the four stereoisomers or each stereoisomer individually (0, 30, or 100 mg/kg/d) by gavage for 28 days. Pathological staining of the liver sections showed that the ( 2R,4R )-isomer caused lipid droplet accumulation. The mixture or each individual stereoisomers decreased the levels of amino acids and acyl-carnitine in serum. Moreover, the ( 2S,4R )-, ( 2R,4R )-, and ( 2R,4S )-isomers affected intestinal permeability, causing decreases in mucus secretion and tight junction protein expression in colon. Analysis of the gut microbiota composition showed that the stereoisomers caused decreases of OTU numbers and observed species at different levels. Interestingly, difenoconazole and its four stereoisomers reduced the relative abundance of Bacteroidetes at the phylum level and some short-chain fatty acid (SCFA)-producing bacteria. Taking the findings together, 2R -difenoconazole with strong bioactivity against pathogenic fungi also had significant effects in mammals, disrupting hepatic lipid metabolism, intestinal permeability, and gut microbiota. It is concluded that the health risks of the four difenoconazole stereoisomers to mammals should not be overlooked.
研究领域:
毒理学
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环境科学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Cuiyuan Jin,Caiyun Wang,Chen Zhang,Qi Ye,Yuanxiang Jin,Liyun Shi
As a fungicide with the characteristics of high effectiveness, internal absorption and broad spectrum, imazalil is widely used to prevent and treat in fruits and vegetables. Here, pregnant C57BL/6 mice were exposed to imazalil at dietary levels of 0, 0.025‰, and 0.25‰ through drinking water during pregnancy and lactation. We then analyzed the phenotype, metabolome, and expression of related genes and proteins in the livers of mice. There was a marked decrease in the body and liver weights of male offspring mice after maternal imazalil exposure, while this effect on the dam and female offspring was slight. Metabolomics analyses revealed that imazalil significantly altered the metabolite composition of liver samples from both dams and offspring. The preliminary results of the analysis indicated that glucolipid metabolism was the pathway most significantly affected by imazalil. We performed a coabundance association analysis of metabolites with significant changes in the pathway of glycolipid metabolism, and IMZ altered the networks of both dams and offspring compared with the network in control mice, especially in male offspring. The hepatic triglyceride, non-esterified fatty acid and glucose levels were increased significantly in the dams but decreased significantly in male offspring after maternal imazalil exposure. Furthermore, the expression levels of genes associated with glycolipid metabolism and m 6 A RNA methylation were significantly affected by maternal intake of imazalil. Imazalil-induced glucolipid metabolism disturbance was highly correlated with m 6 A RNA methylation. In conclusion, maternal imazalil exposure resulted in glucolipid metabolism disturbance and abnormal m 6 A RNA methylation in the livers of dams and offspring mice. We expected that the information acquired in this study will provide novel evidence for understanding the effect of maternal imazalil exposure on potential health risks.
研究领域:
毒理学
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代谢组学
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分子生物学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 20
·3518
·
IF 4.8
Xiaodong Shi,Wei Song,Boyue Jiang,Jie Ma,Wanyang Li,Mingyao Sun,Hongyuan Cui,Wei Chen
Objectives:Highland barley (HB) consumption offers numerous health benefits; however, its impact on glycolipid metabolism abnormalities induced by a high-fat diet remains unclear. Consequently, this study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HB in the context of obesity;Methods:Rats were fed either a high-fat diet (HFD) to induce obesity or a standard diet (SD) for six weeks. The rats in the HFD group were randomly assigned into five groups: HFD+HFD, HFD+SD, and low (30%), medium (45%), and high (60%) doses of the HB diet for an additional ten weeks. Analyses of serum lipid profiles, liver histology, transcriptomes, and untargeted metabolomes were conducted;Results:HB intake resulted in decreased weight gain, reduced feed intake, lower serum triglyceride and cholesterol levels, and diminished hepatic lipid accumulation. It also improved insulin and fasting blood glucose levels, and antioxidant capacity in the HFD-fed rats. Transcriptome analysis revealed that HB supplementation significantly suppressed the HFD-induced increase in the expression of Angptl8, Apof, CYP7A1, GDF15, Marveld1, and Nr0b2. Furthermore, HB supplementation reversed the HFD-induced decrease in Pex11a expression. Untargeted metabolome analysis indicated that HB primarily influenced the pentose phosphate pathway, the Warburg effect, and tryptophan metabolism. Additionally, integrated transcriptome and metabolome analyses demonstrated that the treatments affected the expression of genes associated with glycolipid metabolism, specifically ABCG8, CYP2C12, CYP2C24, CYP7A1, and IRS2. Western blotting confirmed that HB supplementation impacted the IRS2/PI3K/AKT signaling pathway;Conclusions:HB alleviates HFD-induced obesity and liver injury in an obese rat model possibly through the IRS2/PI3K/Akt signaling pathway.
研究领域:
营养学
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分子生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2021
·
IF 7.561
Lu Hanqi,You Yanting,Zhou Xinghong,He Qiuxing,Wang Ming,Chen Liqian,Zhou Lin,Sun Xiaomin,Liu Yanyan,Jiang Pingping,Dai Jiaojiao,Fu Xiuqiong,Kwan Hiu Yee,Zhao Xiaoshan,Lou Linjie
Background: Studies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process.Purpose: The study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated.Methods and Results: Three-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects.Conclusion: Taken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.
研究领域:
药理学
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微生物学
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营养学
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代谢学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Yanhua Wang,Xiaofang Wang,Yu-Cheng Zhu,Dou Wang,Lu Lv,Liezhong Chen,Yuanxiang Jin
Ochratoxin A (OTA) is a mycotoxin , and triadimefon (TDF) is a triazole fungicide . These compounds are prevalent in the environment, and their residues have been detected in crops. However, the precise health risks associated with mycotoxins and fungicides are not fully elucidated. In this work, five-week-old mice were gavage with OTA (0.3 and 1.5 mg/kg/day), TDF (10 and 50 mg/kg/day), and OTA + TDF (0.3 + 10 and 1.5 + 50 mg/kg/day) for 28 days. Exposure to OTA, TDF, and OTA + TDF led to significant alterations in liver total cholesterol (TC), triglyceride (TG), and glucose (GLU) levels, as well as in genes associated with glycolipid metabolism in mice. Reduced acylcarnitine levels in serum indicated that OTA, TDF, and co-exposure inhibited fatty acid (FA) β-oxidation. Furthermore, OTA and TDF disrupted the integrality of the gut barrier function and altered the structure of the intestinal microbiota. These findings suggested that OTA, TDF, and their co-exposure might disrupt the intestinal barrier, alter the structure of the microbiota, and subsequently inhibit FA β-oxidation, indicating the interference of OTA and TDF with glycolipid-related intestinal barrier dysfunction. Moreover, our data revealed a toxic additive effect between OTA and TDF, providing a foundation for assessing the combined toxicity risk of mycotoxins and fungicides.
研究领域:
食品安全
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毒理学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Haiying Cai,Menghui Lin,Kaiyi Chen,Yuanfeng Wu,Thanh Ninh Le,Junhui Zhang,Minjie Zhao
The circulating bile acids (BAs) play critical roles in regulating the glycolipid metabolism, inflammation, and other physiological functions. Male C57BL/6J mice were given high-fat diet (HFD) with 500 mg/kg and 2500 mg/kg caffeic acid phenethyl ester (CAPE) for 16 weeks (CAPE500 and CAPE2500). The results showed that both the two dose of CAPE treatment improved the glycolipid metabolism and inflammation in HFD-induced obese mice. The BA profile analysis revealed that CAPE2500 increased hepatic and serum circulating BA levels compared to HFD ( P- value of 0.347 and 0.467, respectively), while CAPE500 showed decreased serum circulating BA levels compare to CAPE2500 ( P- value of 0.0881), suggesting dose-specific ameliorative mechanisms of CAPE on obesity based on BA signaling. Further study found significantly lower bile salt hydrolase (BSH) activity in the ileal contents of the CAPE500 group compared to the HFD group, which resulted in suppressed intestinal FXR signaling and improved glycolipid metabolism through inhibiting ileal FXR-enhanced ceremide synthesis. However, CAPE2500 increased serum circulating BA levels by significantly decreasing BA excretion compared with the HFD and CAPE500 groups ( P < 0.0001 and P < 0.01, respectively), enhancing brown adipose tissue thermogenesis by activating the TGR5/UCP-1 signaling axis. Furthermore, CAPE also ameliorated the gut microbiota disorders and obesity induced by HFD. This study reveals a dose-specific effect of CAPE treatment on circulating BA content, ileal BSH-FXR signaling and gut microbiota, which improves glucose and lipid dyshomeostasis through different mechanisms.
研究领域:
营养学
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分子生物学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）