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Circulation Research Jun 2024Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence... (Review)
Review
Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes. We further discussed the cellular and molecular mechanisms of arachidonic acid pathway-mediated regulation of cardiometabolic diseases and highlighted the emerging clinical advances to improve these pathological conditions by targeting arachidonic acid metabolites and pathway factors.
Topics: Humans; Arachidonic Acid; Animals; Cardiovascular Diseases; Signal Transduction; Metabolic Diseases; Cardiometabolic Risk Factors; Obesity
PubMed: 38900855
DOI: 10.1161/CIRCRESAHA.124.324383 -
PloS One 2024The motor features of Parkinson's disease result from loss of dopaminergic neurons in the substantia nigra with autophagy dysfunction being closely linked to this...
The motor features of Parkinson's disease result from loss of dopaminergic neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. While a large body of work focusing on protein effectors of autophagy has been reported, regulation of autophagy by lipids has garnered far less attention. Therefore, we sought to identify endogenous lipid molecules that act as signaling mediators of autophagy in differentiated SH-SY5Y cells, a commonly used dopaminergic neuron-like cell model. In order to accomplish this goal, we assessed the role of a fatty acid-binding protein (FABP) family member on autophagy due to its function as an intracellular lipid chaperone. We focused specifically upon FABP5 due to its heightened expression in dopaminergic neurons within the substantia nigra and SH-SY5Y cells. Here, we report that knockdown of FABP5 resulted in suppression of autophagy in differentiated SH-SY5Y cells suggesting the possibility of an autophagic role for an interacting lipid. A lipidomic screen of FABP5-interacting lipids uncovered hits that include 5-oxo-eicosatetraenoic acid (5OE) and its precursor metabolite, arachidonic acid (AA). Additionally, other long-chain fatty acids were found to bind FABP5, such as stearic acid (SA), hydroxystearic acid (HSA), and palmitic acid (PA). The addition of 5OE, SA, and HSA but not AA or PA, led to potent inhibition of autophagy in SH-SY5Y cells. To identify potential molecular mechanisms for autophagy inhibition by these lipids, RNA-Seq was performed which revealed both shared and divergent signaling pathways between the lipid-treated groups. These findings suggest a role for these lipids in modulating autophagy through diverse signaling pathways and could represent novel therapeutic targets for Parkinson's disease.
Topics: Autophagy; Humans; Fatty Acid-Binding Proteins; Cell Line, Tumor; Cell Differentiation; Dopaminergic Neurons; Signal Transduction
PubMed: 38900831
DOI: 10.1371/journal.pone.0300168 -
Environmental Pollution (Barking, Essex... Jun 2024Endocrine disrupting chemicals (EDCs) can disrupt normal endocrine function by interfering with the synthesis and release of hormones, causing adverse reactions to...
Endocrine disrupting chemicals (EDCs) can disrupt normal endocrine function by interfering with the synthesis and release of hormones, causing adverse reactions to development, immunity, nerves, and reproduction. 4-tert-Butylphenol (4-t-BP) is disruptive to early zebrafish development, but its effects on zebrafish liver are unknown. In this study, the adverse effects of 4-t-BP on the liver were investigated using zebrafish as a model organism. 4-t-BP inhibited liver development in zebrafish embryos and induced liver damage in adult zebrafish. Even if F1 was not directly exposed to 4-t-BP, its growth and development were inhibited. 4-t-BP can lead to an increase in lipid accumulation, total cholesterol and triglycerides contents, and the activities of alanine transaminase and aspartate aminotransferase in zebrafish embryos and adult zebrafish livers, and also cause an acceleration of glucose metabolism in zebrafish embryos. In addition, qRT-PCR showed that 4-t-BP induced the changes in the expressions of liver development-, steroid and unsaturated fatty acid biosynthesis-, and glycerolipid and arachidonic acid metabolism-related genes in zebrafish embryos and inflammatory factors-, antioxidant enzymes- and lipid metabolism-related genes in adult zebrafish livers. Transcriptome sequencing of embryos showed that 4-t-BP altered the expressions of lipid metabolism pathways such as steroid and unsaturated fatty acid biosynthesis, glycerolipid, and arachidonic acid metabolism pathways. Therefore, 4-t-BP may be external stimuli that cause oxidative stress, inflammation, and lipid accumulation in zebrafish liver, resulting in tissue damage and dysfunction in zebrafish liver.
PubMed: 38897274
DOI: 10.1016/j.envpol.2024.124385 -
Ecotoxicology and Environmental Safety Jun 2024Irritable bowel syndrome (IBS) patients exhibit significantly lower levels of serum selenium (Se) compared to healthy controls. This study integrates a prospective...
Irritable bowel syndrome (IBS) patients exhibit significantly lower levels of serum selenium (Se) compared to healthy controls. This study integrates a prospective cohort analysis and animal experiments to investigate Se deficiency as a potential risk factor for IBS. Using data from the UK Biobank, a longitudinal analysis was conducted to explore the associations between dietary Se intake and the risk of incident IBS. In animal study, C57BL/6 mice were fed diets with normal (0.2 ppm) or low (0.02 ppm) Se levels to assess the impacts of Se deficiency on IBS symptoms. Furthermore, we performed 16 S rRNA sequencing, untargeted colonic fecal metabolomics analysis, and colon transcriptome profiling to uncover the regulatory mechanisms underlying Se deficiency-induced IBS. The analysis of UK Biobank data revealed a significant correlation between low dietary Se levels and an increased incidence of IBS. In the experimental study, a low Se diet induced IBS symptoms, evidenced by elevated abdominal withdrawal reflex scores, colon inflammation, and severe pathological damage to the colon. Additionally, the low Se diet caused disturbances in gut microbiota, characterized by an increase in Faecalibaculum and Helicobacter, and a decrease in Bifidobacterium and Akkermansia. Combined colonic fecal metabolomics and colon transcriptome analysis indicated that Se deficiency might trigger IBS through disruptions in pathways related to "bile excretion", "steroid hormone biosynthesis", "arachidonic acid metabolism", and "drug metabolism-cytochrome P450". These findings underscore the significant adverse effects of Se deficiency on IBS and suggest that Se supplementation should be considered for IBS patients.
PubMed: 38896900
DOI: 10.1016/j.ecoenv.2024.116604 -
Ecology and Evolution Jun 2024The mangrove fish () serves as a model for researching environmental adaptation and sexual development. To further such research, we sequenced and assembled a...
The mangrove fish () serves as a model for researching environmental adaptation and sexual development. To further such research, we sequenced and assembled a high-quality 842 Mb reference genome for . Comparative genomic analysis revealed 891 expanded gene families, including significantly expanded cytochrome P450 () detoxification genes known to be involved in xenobiotic defense. We identified 69 () across 18 families and 10 clans using multiple methods. Extensive RNA-seq and qPCR analysis demonstrated diverse spatiotemporal expression patterns of by developmental stage, tissue type, sex, and pollutant exposure (17β-estradiol (E2) and testosterone (MT)). Many exhibited sexual dimorphism in gonads, suggesting reproductive roles in steroidogenesis, while their responsiveness to model toxicants indicates their importance in environmental adaptation through enhanced detoxification. Pathway analysis highlighted expanded genes in arachidonic acid metabolism, drug metabolism, and steroid hormone biosynthesis. This chromosome-level genomic resource provides crucial biological insights to elucidate the functional roles of expanded in environmental adaptation, sexual development, early life history, and conservation in the anthropogenically impacted mangrove habitats of . It also enables future ecotoxicology research leveraging as a pollution sentinel species.
PubMed: 38895576
DOI: 10.1002/ece3.11565 -
Cancers May 2024This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and... (Review)
Review
This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered. The review begins by discussing the properties of these enzymes, emphasizing their specificity in enzymatic reactions, notably the incorporation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid (DHA) into phospholipids. The paper sheds light on the intricate involvement of these enzymes in various diseases, including obesity, insulin resistance, and cancer. To underscore the relevance of these enzymes in cancer processes, a bioinformatics analysis was conducted. The expression levels of the described enzymes were correlated with the overall survival of patients across 33 different types of cancer using the GEPIA portal. This review further explores the potential therapeutic implications of inhibiting these enzymes in the treatment of metabolic diseases and cancer. By elucidating the intricate enzymatic pathways involved in lipid synthesis and their impact on various pathological conditions, this paper contributes to a comprehensive understanding of these processes and their potential as therapeutic targets.
PubMed: 38893234
DOI: 10.3390/cancers16112115 -
Nutrients May 2024An imbalance of energy intake and expenditure is commonly considered as the fundamental cause of obesity. However, individual variations in susceptibility to obesity do...
An imbalance of energy intake and expenditure is commonly considered as the fundamental cause of obesity. However, individual variations in susceptibility to obesity do indeed exist in both humans and animals, even among those with the same living environments and dietary intakes. To further explore the potential influencing factors of these individual variations, male C57BL/6J mice were used for the development of obesity-prone and obesity-resistant mice models and were fed high-fat diets for 16 weeks. Compared to the obesity-prone mice, the obesity-resistant group showed a lower body weight, liver weight, adipose accumulation and pro-inflammatory cytokine levels. 16S rRNA sequencing, which was conducted for fecal microbiota analysis, found that the fecal microbiome's structural composition and biodiversity had changed in the two groups. The genera , , and increased in the obesity-prone mice, and the genera , and were enriched in the obesity-resistant mice. Using widely targeted metabolomics analysis, 166 differential metabolites were found, especially those products involved in arachidonic acid (AA) metabolism, which were significantly reduced in the obesity-resistant mice. Moreover, KEGG pathway analysis exhibited that AA metabolism was the most enriched pathway. Significantly altered bacteria and obesity-related parameters, as well as AA metabolites, exhibited strong correlations. Overall, the phenotypes of the obesity-prone and obesity-resistant mice were linked to gut microbiota and AA metabolism, providing new insight for developing an in-depth understanding of the driving force of obesity resistance and a scientific reference for the targeted prevention and treatment of obesity.
Topics: Animals; Gastrointestinal Microbiome; Diet, High-Fat; Obesity; Male; Mice, Inbred C57BL; Arachidonic Acid; Mice; Feces; RNA, Ribosomal, 16S; Disease Models, Animal; Bacteria; Body Weight
PubMed: 38892512
DOI: 10.3390/nu16111579 -
Plants (Basel, Switzerland) May 2024is a perennial plant well known for its versatile medicinal properties, including hepatoprotective, antioxidant, anti-inflammatory, anti-tumor, estrogen-like, and...
is a perennial plant well known for its versatile medicinal properties, including hepatoprotective, antioxidant, anti-inflammatory, anti-tumor, estrogen-like, and antidepressant characteristics. It has been reported that plant age affects the quality of . This study aimed to explore the differential metabolome and transcriptome of 2-year (PN2) and 3-year-old (PN3) plant root samples. Principal component analysis of metabolome and transcriptome data revealed major differences between the two groups (PN2 vs. PN3). A total of 1813 metabolites and 28,587 genes were detected in this study, of which 255 metabolites and 3141 genes were found to be differential ( < 0.05) between PN2 vs. PN3, respectively. Among differential metabolites and genes, 155 metabolites and 1217 genes were up-regulated, while 100 metabolites and 1924 genes were down-regulated. The KEGG pathway analysis revealed differentially enriched metabolites belonging to class lipids ("13S-hydroperoxy-9Z, 11E-octadecadionic acid", "9S-hydroxy-10E, 12Z-octadecadionic acid", "9S-oxo-10E, 12Z-octadecadionic acid", and "9,10,13-trihydroxy-11-octadecadionic acid"), nucleotides and derivatives (guanine and cytidine), and phenolic acids (chlorogenic acid) were found to be enriched ( < 0.05) in PN3 compared to PN2. Further, these differentially enriched metabolites were found to be significantly ( < 0.05) regulated via linoleic acid metabolism, nucleotide metabolism, plant hormone signal transduction, and arachidonic acid metabolism pathways. Furthermore, the transcriptome analysis showed the up-regulation of key genes , , , gallate 1-beta-glucosyltransferase, and beta-D-glucosidase in various plants' secondary metabolic pathways and , , , , , , and genes observed in phytohormone signal transduction pathway that is involved in plant growth and development, and protection against the various stressors. This study concluded that the roots of a 3-year-old plant have better metabolome and transcriptome profiles compared to a 2-year-old plant with importantly enriched metabolites and genes in pathways related to metabolism, plant hormone signal transduction, and various biological processes. These findings provide insights into the plant's dynamic biochemical and molecular changes during its growth that have several implications regarding its therapeutic use.
PubMed: 38891250
DOI: 10.3390/plants13111441 -
Foods (Basel, Switzerland) May 2024Edible crickets have recently been used as a new alternative protein source with high nutritional value. The nutritional and flavor-related value of edible crickets...
Edible crickets have recently been used as a new alternative protein source with high nutritional value. The nutritional and flavor-related value of edible crickets varies greatly depending on the species, growth conditions and processing conditions. However, few studies have investigated the effects of the diet fed to crickets during their growth phase on flavor. Therefore, in this study, we characterized the flavor-related factors of powder from crickets reared on apple by-products (ACP) by comparing them with those of powder from crickets reared on a control diet (CCP). The fatty acid composition and volatile compounds of each powder were determined using gas chromatography and mass spectrometry, followed by sensory analysis and color measurement. A decrease in unsaturated fatty acids, specifically γ-linolenic acid, α-linolenic acid, arachidonic acid and docosahexaenoic acid, was observed in ACP. A total of 50 volatile compounds were identified, of which 11 were present in only ACP, while 39 were found in both powders. The sensory analysis showed that the overall balance score of ACP was higher than that of CCP, and according to the color measurements, ACP was darker than CCP. These differences between CCP and ACP might have been due to the differences in the chemical composition of the diets fed to the crickets during their growth phase. The results of this study suggest that one of the factors determining the food value of edible crickets, especially in terms of flavor, is the diet they are fed during their growth phase.
PubMed: 38890896
DOI: 10.3390/foods13111668 -
Journal of Pharmaceutical and... May 2024Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign...
Integrated network pharmacology and serum metabonomics analysis to explore the potential mechanism of Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid herb pair in the treatment of benign prostatic hyperplasia.
Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.
PubMed: 38889577
DOI: 10.1016/j.jpba.2024.116264