Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies

Guan, Xin‐Xin; Rao, Dongning; Liu, Yan-Zhe; Zhou, Yong; Yang, Huihui

doi:10.3390/ijms221910714

Cited by 16 publications

(12 citation statements)

References 85 publications

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“…As n-6/n-3 PUFA ratio in diet increases, some n-6 PUFA such as eicosatetraenoic acid increases and it was positively correlated with Slackia and Sporobacter . Eicosatetraenoic acid is a kind of biological active substance, which plays an important role in regulating the metabolism of lipid protein ( Guan et al, 2021 ). These results indicated that the lower n-6/n-3 PUFA ratio could regulate the absorption and release of PUFA and protect gut health in pigs.…”

Section: Discussionmentioning

confidence: 99%

Changes in Serum Fatty Acid Composition and Metabolome-Microbiome Responses of Heigai Pigs Induced by Dietary N-6/n-3 Polyunsaturated Fatty Acid Ratio

Wang

Nong²,

Zhou³

et al. 2022

Front. Microbiol.

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Changing fatty acid composition is a potential nutritional strategy to shape microbial communities in pigs. However, the effect of different n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on serum fatty acid composition, microbiota, and their metabolites in the intestine of pigs remains unclear. Our study investigated the changes in serum fatty acid composition and metabolome–microbiome responses induced by dietary n-6/n-3 PUFA ratio based on a Heigai-pig model. A total of 54 Heigai finishing pigs (body weight: 71.59 ± 2.16 kg) fed with 3 types of diets (n-6/n-3 PUFA ratios are 8:1, 5:1, and 3:1) were randomly divided into 3 treatments with 6 replications (3 pigs per replication) for 75 days. Results showed that dietary n-6/n-3 PUFA ratio significantly affected biochemical immune indexes including glucose (Glu), triglycerides (TG), total cholesterol (TChol), non-esterified fatty acid (NEFA), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total thyroxine (TT4), and medium- and long-chain fatty acid composition, especially n-3 PUFA and n-6/n-3 PUFA ratio in the serum. However, no significant effects were found in the SCFAs composition and overall composition of the gut microbiota community. In the low dietary n-6/n-3 PUFA ratio group, the relative abundance of Cellulosilyticum, Bacteroides, and Alloprevotella decreased, Slackia and Sporobacter increased. Based on the metabolomic analysis, dietary n-6/n-3 PUFA ratio altered the metabolome profiles in the colon. Moreover, Pearson’s correlation analysis indicated that differential microbial genera and metabolites induced by different n-6/n-3 PUFA ratio had tight correlations and were correlated with the n-6 PUFA and n-3 PUFA content in longissimus dorsi muscle (LDM) and subcutaneous adipose tissue (SAT). Taken together, these results showed that lower dietary n-6/n-3 PUFA ratio improved serum fatty acid composition and metabolome–microbiome responses of Heigai pigs and may provide a new insight into regulating the metabolism of pigs and further better understanding the crosstalk with host and microbes in pigs.

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Section: Discussionmentioning

confidence: 99%

Changes in Serum Fatty Acid Composition and Metabolome-Microbiome Responses of Heigai Pigs Induced by Dietary N-6/n-3 Polyunsaturated Fatty Acid Ratio

Wang

Nong²,

Zhou³

et al. 2022

Front. Microbiol.

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“…CYP450 enzyme, lipoxygenase (LOX) and cyclooxygenase (COX) are the main metabolic enzymes of lipid, and the products of polyunsaturated fatty acids (PUFA) catalyzed by these three enzymes are signaling molecules of endogenous lipid metabolism [52]. PUFA products of CYP450 mainly include a variety of epoxide fatty acids (EpFAs) and arachidonic acid products, both of which are important lipid signaling molecules involved in lipid regulation [53]. More research is needed to confirm the relationship between CYP2C19 genotypes and serum lipid level in the future.…”

Section: Discussionmentioning

confidence: 99%

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

Cai

et al. 2023

BMC Cardiovasc Disord

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Background Genetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population. Methods The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. Results The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P < 0.001), and CYP2C19*2 allele (33.8% vs. 25.7%, P < 0.001) in hypertension group was significantly higher than that in control group. Multivariate logistic regression (adjusted for gender, age, smoking, and drinking) indicated that CYP2C19 *1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And the CYP2C19 IM genotype (IM vs. EM: OR 1.514, 95% CI: 1.291–1.775, P < 0.001), PM genotype (PM vs. EM: OR 2.120, 95% CI: 1.638–2.743, P < 0.001), IM + PM genotypes (IM + PM vs. EM: OR 1.617, 95% CI: 1.390–1.882, P < 0.001) may increase risk of hypertension. Conclusions CYP2C19 loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes include CYP2C19 *1/*2, *1/*3, and *2/*2.

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“…CYP2J2 and EETs have been repeatedly demonstrated to possess protective effects against various cardiovascular diseases. Previous reports have described the function of EETs during cardiac remodeling inhibition in cardiac hypertrophy, fibrosis, angiogenesis, inflammation, and apoptosis [ 49 , 50 ]. The findings of another study indicated that overexpression of CYP2J2 promoted the production of EET, alleviated cardiac function impairment, and enhanced the fibrotic response in CYP2J2 transgenic mice [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers Associated with Heart Failure Caused by Idiopathic Dilated Cardiomyopathy Using WGCNA and Machine Learning Algorithms

Sun

2023

International Journal of Genomics

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Background. The genetic factors and pathogenesis of idiopathic dilated cardiomyopathy-induced heart failure (IDCM-HF) have not been understood thoroughly; there is a lack of specific diagnostic markers and treatment methods for the disease. Hence, we aimed to identify the mechanisms of action at the molecular level and potential molecular markers for this disease. Methods. Gene expression profiles of IDCM-HF and non-heart failure (NF) specimens were acquired from the database of Gene Expression Omnibus (GEO). We then identified the differentially expressed genes (DEGs) and analyzed their functions and related pathways by using “Metascape”. Weighted gene co-expression network analysis (WGCNA) was utilized to search for key module genes. Candidate genes were identified by intersecting the key module genes identified via WGCNA with DEGs and further screened via the support vector machine-recursive feature elimination (SVM-RFE) method and the least absolute shrinkage and selection operator (LASSO) algorithm. At last, the biomarkers were validated and evaluated the diagnostic efficacy by the area under curve (AUC) value and further confirmed the differential expression in the IDCM-HF and NF groups using an external database. Results. We detected 490 genes exhibiting differential expression between IDCM-HF and NF specimens from the GSE57338 dataset, with most of them being concentrated in the extracellular matrix (ECM) of cells related to biological processes and pathways. After screening, 13 candidate genes were identified. Aquaporin 3 (AQP3) and cytochrome P450 2J2 (CYP2J2) showed high diagnostic efficacy in the GSE57338 and GSE6406 datasets, respectively. In comparison to the NF group, AQP3 was significantly down-regulated in the IDCM-HF group, while CYP2J2 was significantly up-regulated. Conclusion. As far as we know, this is the first study that combines WGCNA and machine learning algorithms to screen for potential biomarkers of IDCM-HF. Our findings suggest that AQP3 and CYP2J2 could be used as novel diagnostic markers and treatment targets of IDCM-HF.

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Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies

Cited by 16 publications

References 85 publications

Changes in Serum Fatty Acid Composition and Metabolome-Microbiome Responses of Heigai Pigs Induced by Dietary N-6/n-3 Polyunsaturated Fatty Acid Ratio

Changes in Serum Fatty Acid Composition and Metabolome-Microbiome Responses of Heigai Pigs Induced by Dietary N-6/n-3 Polyunsaturated Fatty Acid Ratio

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

Identification of Biomarkers Associated with Heart Failure Caused by Idiopathic Dilated Cardiomyopathy Using WGCNA and Machine Learning Algorithms

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