Disruption Of Lipid Metabolism Research Articles

Bacteroides fragilis aggravates high-fat diet-induced non-alcoholic fatty liver disease by regulating lipid metabolism and remodeling gut microbiota.

Gut microbiota dysbiosis is a prominent determinant that significantly contributes to the disruption of lipid metabolism. Consequently, it is essential to the occurrence and development of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the connection between diet and symbiotic gut microbiota in the progression of NAFLD remains uncertain. The purpose of this study was to explore the role of supplementing commensal Bacteroides fragilis (B. fragilis) on lipid metabolism, gut microbiota, and metabolites in high-fat diet (HFD)-fed mice, elucidating the impact of gut microbiota and metabolites on the development of NAFLD. Our study revealed that supplementation with B. fragilis exacerbated both weight gain and obesity in mice. B. fragilis exacerbated blood glucose levels and liver dysfunction in mice. Furthermore, an increase in liver lipid accumulation and the upregulation of genes correlated with lipid metabolism were observed in mice. Under an HFD, supplementation of commensal B. fragilis resulted in alterations in the gut microbiota, notably a significant increase in Desulfovibrionaceae, which led to elevated endotoxin levels and thereby influenced the progression of NAFLD. It was interesting that the simultaneous examination of gut microbiota metabolites revealed a more pronounced impact of diet on short-chain fatty acids. This study represented the pioneering investigation into the impact of B. fragilis on NAFLD. Our findings demonstrated that B. fragilis induced dysregulation in the intestinal microbiota, leading to elevated levels of lipopolysaccharide and dysfunction in glucose and lipid metabolism, thereby exacerbating NAFLD.IMPORTANCESome intestinal symbiotic microbes are involved in the occurrence of the metabolic disorders. Our study investigated the impact of supplementing commensal Bacteroides fragilis on host metabolism in high-fat diet-fed mice. Research results indicated that adding a specific bacterial strain to the complex intestinal microecology can worsen metabolic conditions. This effect mainly affects the structural diversity of intestinal microorganisms, the increase in harmful bacteria in the gut, and the elevation of endotoxin levels, blood glucose, and lipid metabolism, thereby impacting the progression of non-alcoholic fatty liver disease (NAFLD). Understanding the principles that govern the establishment of microbial communities comprising multiple species is crucial for preventing or repairing dysfunctions in these communities, thereby enhancing host health and facilitating disease treatment. This study demonstrated that gut microbiota dysbiosis could contribute to metabolic dysfunction and provides new insights into how to promote gut microbiota in the prevention and therapy of NAFLD.

PCSK9i promoting the transformation of AS plaques into a stable plaque by targeting the miR-186-5p/Wipf2 and miR-375-3p/Pdk1/Yap1 in ApoE-/- mice.

Atherosclerosis (AS) is a multifaceted disease characterized by disruptions in lipid metabolism, vascular inflammation, and the involvement of diverse cellular constituents. Recent investigations have progressively underscored the role of microRNA (miR) dysregulation in cardiovascular diseases, notably AS. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can effectively reduce circulating levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp (a)], potentially fostering a more enduring phenotype for AS plaques. However, the underlying mechanisms by which PCSK9i enhances plaque stability remain unclear. In this study, we used microarray and bioinformatics techniques to analyze the regulatory impacts on gene expression pertinent to AS, thereby unveiling potential mechanisms underlying the plaque-stabilizing attributes of PCSK9i. ApoE-/- mice were randomly allocated into control, AS, PCSK9i, and Atorvastatin groups. The AS model was induced through a high-fat diet (HFD), succeeded by interventions: the PCSK9i group was subjected to subcutaneous SBC-115076 injections (8 mg/kg, twice weekly), and the Atorvastatin group received daily oral Atorvastatin (10 mg/kg) while on the HFD. Subsequent to the intervention phase, serum analysis, histological assessment using hematoxylin and eosin (H&E) and Oil Red O staining, microarray-centered miRNA analysis utilizing predictions from TargetScan and miRTarBase, and analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were executed to illuminate potential pathways. Real-time fluorescence quantitative PCR (RT-qPCR) was employed to quantify the expression levels of target genes. In comparison to the control group, the AS group displayed a significant elevation in blood lipid levels. Both PCSK9i and Atorvastatin effectively attenuated blood lipid levels, with PCSK9i exhibiting a more pronounced lipid-lowering impact, particularly concerning TG and LDL-C levels. Over the course of AS progression, the expression levels of mmu-miR-134, mmu-miR-141-5p, mmu-miR-17-3p, mmu-miR-195-3p, mmu-miR-210, mmu-miR-33-5p, mmu-miR-410, mmu-miR-411-5p, mmu-miR-499, mmu-miR-672-5p, mmu-miR-675-3p, and mmu-miR-301b underwent dynamic fluctuations. PCSK9i significantly down-regulated the expression of mmu-miR-186-5p, mmu-miR-222, mmu-miR-375-3p, and mmu-miR-494-3p. Further enrichment analysis disclosed that mmu-miR-186-5p, mmu-miR-222, mmu-miR-375-3p, and mmu-miR-494-3p were functionally enriched for cardiovascular smooth muscle cell proliferation, migration, and regulation. RT-qPCR results manifested that, in comparison to the AS group, PCSK9i significantly upregulated the expression of Wipf2, Pdk1, and Yap1 (p < 0.05). Aberrant miRNA expression may play a pivotal role in AS progression in murine models of AS. The subcutaneous administration of PCSK9i exerted anti-atherosclerotic effects by targeting the miR-186-5p/Wipf2 and miR-375-3p/Pdk1/Yap1 axes, thereby promoting the transition of AS plaques into a more stable form.

Molecular Behavior of α-Synuclein Is Associated with Membrane Transport, Lipid Metabolism, and Ubiquitin-Proteasome Pathways in Lewy Body Disease.

Lewy body diseases (LBDs) feature α-synuclein (α-syn)-containing Lewy bodies, with misfolded α-syn potentially propagating as seeds. Using a seeding amplification assay, we previously reported distinct α-syn seeding in LBD cases based on the area under seeding curves. This study revealed that LBD cases showing different α-syn seeding kinetics have distinct proteomics profiles, emphasizing disruptions in mitochondria and lipid metabolism in high-seeder cases. Though the mechanisms underlying LBD development are intricate, the factors influencing α-syn seeding activity remain elusive. To address this and complement our previous findings, we conducted targeted transcriptome analyses in the substantia nigra using the nanoString nCounter assay together with histopathological evaluations in high (n = 4) and low (n = 3) nigral α-syn seeders. Neuropathological findings (particularly the substantia nigra) were consistent between these groups and were characterized by neocortical LBD associated with Alzheimer's disease neuropathologic change. Among the 1811 genes assessed, we identified the top 20 upregulated and downregulated genes and pathways in α-syn high seeders compared with low seeders. Notably, alterations were observed in genes and pathways related to transmembrane transporters, lipid metabolism, and the ubiquitin-proteasome system in the high α-syn seeders. In conclusion, our findings suggest that the molecular behavior of α-syn is the driving force in the neurodegenerative process affecting the substantia nigra through these identified pathways. These insights highlight their potential as therapeutic targets for attenuating LBD progression.

Mechanism of Action of the Plateau-Adapted Gene PPARA in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex respiratory disorder influenced by various factors and involving multiple genes. Respiratory dysfunction in COPD patients leads to hypoxia, resulting in limited oxygen uptake. Peroxisome proliferator-activated receptor alpha (PPARA) is a plateau-adapted gene that regulates respiratory function in populations adapted to high-altitude areas through multiple pathways. Interestingly, PPARA expression is higher in long-term inhabiting Tibetan populations that have adapted to the plateau environment. However, in patients with COPD, the expression of PPARA is downregulated, leading to dysregulation of the hypoxia-inducible factor pathway. Moreover, abnormal PPARA expression in lung epithelial cells triggers inflammatory responses, oxidative stress, and disrupted lipid metabolism, thereby exacerbating disease progression. Thus, this paper explored the mechanism underlying the role of plateau-adapted PPARA in COPD, providing essential theoretical insights into the treatment and prevention of COPD in high-altitude regions.

Chronic exposure to 3,6-dichlorocarbazole exacerbates non-alcoholic fatty liver disease in zebrafish by disrupting lipid metabolism and inducing special lipid biomarker accumulation

Most previous studies have focused primarily on the adverse effects of environmental chemicals on organisms of good healthy. Although global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached approximately 25%, the impact of environmentally persistent organic chemicals on organisms with NAFLD is substantially unknown. Polyhalogenated carbazoles (PHCZs) as emerging contaminants have been frequently detected in the environment and organisms. In this study, we investigated the impact of the most frequently detected PHCZs, 3,6-dichlorocarbazole (36-CCZ), on zebrafish with high-fat diet (HFD)-induced NAFLD. After 4 weeks exposure to environmentally relevant concentrations of 36-CCZ (0.16–0.45 μg/L), the accumulation of lipid in zebrafish liver dramatically increased, and the transcription of genes involved in lipid synthesis, transport and oxidation was significantly upregulated, demonstrating that 36-CCZ had exacerbated the NAFLD in zebrafish. Lipidomic analysis indicated that 36-CCZ had significantly affected liver lipid metabolic pathways, mainly including glycerolipids and glycerophospholipids. Additionally, fifteen lipids were identified as potential lipid biomarkers for 36-CCZ exacerbation of NAFLD, including diacylglycerols (DGs), triglycerides (TGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidic acid (PA), and phosphatidylinositol (PI). These findings demonstrate that long-term exposure to 36-CCZ can promote the progression of NAFLD, which will contribute to raising awareness of the health risks of PHCZs.

Exploring the Influence of the Selected Conjugated Fatty Acids Isomers and Cancerous Process on the Fatty Acids Profile of Spleen

The spleen, traditionally associated with blood filtration and immune surveillance, has recently been recognized for its role in systemic lipid metabolism and potential influence on cancer development and progression. This study investigates effects of dietary supplements, specifically conjugated linolenic acids from pomegranate seed oil and bitter melon extract, on the fatty acid (FA) composition of the spleen in the context of cancerous processes. Advanced methods, including gas chromatography–mass spectrometry and silver ion-impregnated high-performance liquid chromatography, were employed to analyze the spleen’s FA profile. Our research uncovered that dietary supplementation leads to alterations in the spleen’s FA profile, especially under the carcinogenic influence of 7,12-dimethylbenz[a]anthracene. These changes did not align with a simple protective or anti-carcinogenic pattern, as previously suggested in in vitro studies. We observed shifts in conjugated FA isomer concentrations and variations in desaturase activities, suggesting disrupted lipid metabolism in cancerous conditions. The findings underscore the spleen’s vital role in lipid metabolism within the body’s systemic health framework, highlighting the complexity of dietary supplements’ impact on FA profiles in the spleen and their potential implications in cancer progression and treatment. This study adds valuable insight into the complex interplay between diet, disease, and metabolic regulation, particularly in cancerous environments.

Methylparaben induces hepatic glycolipid metabolism disorder by activating the IRE1α-XBP1 signaling pathway in male mice

Methylparaben (MP), a preservative widely used in daily supplies, exists in both the environment and the human body. However, the potential health risks posed by MP remain unclear. This study aimed to unravel the mechanisms by which MP disrupts glucose and lipid homeostasis. For this, we administered MP to mice and observed changes in glucose and lipid metabolism. MP exposure led to hyperglycemia, hyperlipidemia, visceral organ injury, and hepatic lipid accumulation. RNA sequencing results from mice livers indicated a close association between MP exposure and endoplasmic reticulum (ER) stress, inflammatory response, and glucose and lipid homeostasis. Western blotting and quantitative reverse transcription–polymerase chain reaction revealed that MP activated ER stress, particularly the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) pathway, which further promoted the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways phosphorylated insulin receptor substrate-1 (IRS1) (ser 307), resulting in decreased phosphorylation of protein kinase B (Akt) (ser 473), leading to insulin resistance. Additionally, MP exposure promoted lipogenesis through ER stress. To explore potential remedies, we administered the ER stress inhibitor 4-phenylbutyric acid (4-PBA) and the IRE1α-XBP1 pathway inhibitor toyocamycin to mice, both of which protected against metabolic disorders and organ injury caused by MP. These findings suggest that MP induces disruptions in glucose and lipid metabolism through ER stress, primarily through the IRE1α-XBP1 pathway.

Optimizing Predictive Performance: Hyperparameter Tuning in Stacked Multi-Kernel Support Vector Machine Random Forest Models for Diabetes Identification

This study addresses the necessity for more advanced diagnostic tools in managing diabetes, a chronic metabolic disorder that leads to disruptions in glucose, lipid, and protein metabolism caused by insufficient insulin activity. The research investigates the innovative application of machine learning models, specifically Stacked Multi-Kernel Support Vector Machines Random Forest (SMKSVM-RF), to determine their effectiveness in identifying complex patterns in medical data. The innovative ensemble learning method SMKSVM-RF combines the strengths of Support Vector Machines (SVMs) and Random Forests (RFs) to leverage their diversity and complementary features. The SVM component implements multiple kernels to identify unique data patterns, while the RF component consists of an ensemble of decision trees to ensure reliable predictions. Integrating these models into a stacked architecture allows SMKSVM-RF to enhance the overall predictive performance for classification or regression tasks by optimizing their strengths. A significant finding of this study is the introduction of SMKSVM-RF, which displays an impressive 73.37% accuracy rate in the confusion matrix. Additionally, its recall is 71.62%, its precision is 70.13%, and it has a noteworthy F1-Score of 71.34%. This innovative technique shows potential for enhancing current methods and developing into an ideal healthcare system, signifying a noteworthy step forward in diabetes detection. The results emphasize the importance of sophisticated machine learning methods, highlighting how SMKSVM-RF can improve diagnostic precision and aid in the continual advancement of healthcare systems for more effective diabetes management.

Assessment of Lipid Profile in Hepatocellular Carcinoma Patients: A Prospective Study In Bangladesh

Background: Hepatocellular carcinoma (HCC) is a significant cause of cancer-related mortality globally, with a high incidence in Bangladesh. Disruptions in lipid metabolism are a hallmark of liver diseases, including HCC. Understanding the lipid profile in HCC patients can provide insights into the disease's pathophysiology and aid in developing diagnostic and therapeutic strategies. Objective: This study aims to assess the lipid profile in HCC patients in Bangladesh to identify potential diagnostic markers and understand the metabolic alterations associated with the disease. Method: A prospective study was conducted on 356 HCC patients admitted to IBN Sina Specialized Hospital, Dhaka, between June 2022 and December 2023. Blood samples were collected to measure total cholesterol levels, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The lipid profiles of these patients were compared with a control group of healthy individuals. Results: HCC patients exhibited significant alterations in their lipid profiles compared to the control group. Total cholesterol increased by 18.3% (220 mg/dL vs. 186 mg/dL), triglycerides by 25% (190 mg/dL vs. 152 mg/dL), LDL cholesterol by 29.6% (140 mg/dL vs. 108 mg/dL), and HDL cholesterol decreased by 22.4% (38 mg/dL vs. 49 mg/dL) (p&lt;0.001). Advanced tumor stages showed an additional 10% reduction in HDL and a 15% increase in LDL. Impaired liver function led to a further 12% rise in total cholesterol and 20% in triglycerides. These lipid changes were significantly associated with HCC progression and poorer prognosis. Conclusions: The study demonstrates significant dyslipidemia in HCC patients, suggesting that lipid profile alterations could serve as potential biomarkers for early detection and prognosis of HCC. Further research into lipid metabolism pathways in HCC could lead to novel therapeutic targets.

Endocrine Control of Lipid Metabolism.

Lipids are essential in insects and play pleiotropic roles in energy storage, serving as a fuel for energy-driven processes such as reproduction, growth, development, locomotion, flight, starvation response, and diapause induction, maintenance, and termination. Lipids also play fundamental roles in signal transduction, hormone synthesis, forming components of the cell membrane, and thus are essential for maintenance of normal life functions. In insects, the neuroendocrine system serves as a master regulator of most life activities, including growth and development. It is thus important to pay particular attention to the regulation of lipid metabolism through the endocrine system, especially when considering the involvement of peptide hormones in the processes of lipogenesis and lipolysis. In insects, there are several lipogenic and lipolytic hormones that are involved in lipid metabolism such as insulin-like peptides (ILPs), adipokinetic hormone (AKH), 20-hydroxyecdysone (20-HE), juvenile hormone (JH), and serotonin. Other neuropeptides such as diapause hormone-pheromone biosynthesis activating neuropeptide (DH-PBAN), CCHamide-2, short neuropeptide F, and the cytokines Unpaired 1 and 2 may play a role in inducing lipogenesis. On the other hand, neuropeptides such as neuropeptide F, allatostatin-A, corazonin, leukokinin, tachykinins, limostatins, and insulin-like growth factor (ILP6) stimulate lipolysis. This chapter briefly discusses the current knowledge of the endocrine regulation of lipid metabolism in insects that could be utilized to reveal differences between insects and mammalian lipid metabolism whichmay help understand human diseases associated with dysregulation of lipid metabolism. Physiological similarities of insects to mammals make them valuable model systems for studying human diseases characterized by disrupted lipid metabolism, including conditions like diabetes, obesity, arteriosclerosis, and various metabolic syndromes.

Exacerbation of atherosclerosis, hyperlipidemia and inflammation by MK886, an inhibitor of leukotriene biosynthesis, in obese and diabetic mice

Leukotrienes are potent mediators of the inflammatory response and 5-lipoxygenase, the enzyme responsible for their synthesis, is dependent on its interaction with 5-lipoxygenase activating protein for optimum catalysis. Previous studies had demonstrated that macrophage infiltration into adipose tissue is associated with obesity and atherosclerosis in LDLR−/− mice fed a high fat-high carbohydrate. The present study was undertaken to determine whether inhibition of 5-lipoxygenase activating protein is efficacious in attenuating adipose tissue inflammation in LDLR−/− mice fed a high fat-high carbohydrate. 10-week old male LDLR−/− mice were fed a high fat-high carbohydrate diet for 22-weeks, with or without MK886 (40 mg/kg/day, ad libitum) a well-established 5-lipoxygenase activating protein inhibitor. All mice had an approximate 2-fold increase in total body weight, but a 6-week course of MK886 treatment had differential effects on adipose tissue size, without affecting macrophage accumulation. MK886 exacerbated the dyslipidemia, increased serum amyloid A content of high-density lipoproteins and caused a profound hepatomegaly. Dyslipidemia and increased serum amyloid A were concomitant with increases in atherosclerosis. In conclusion, MK886 paradoxically exacerbated hyperlipidemia and the pro-inflammatory phenotype in a mouse model of diet-induced atherosclerosis, possibly via a disruption of hepatic lipid metabolism and increased inflammation.

Disruption of lipid metabolism to induce ferroptosis by multifunctional fibrate-Pt(IV) prodrugs for cancer treatment

Ferroptosis is an iron-mediated regulated cell death initiated by excessive membrane lipid peroxide accumulation. The intimate interplay between ferroptosis and lipid metabolism suggests that modulating lipid metabolism and activating ferroptosis...

New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is increasingly recognized as being intertwined with the dysregulation of lipid metabolism. Lipids are a significant class of nutrients vital to all organisms, playing crucial roles in cellular structure, energy storage, and signaling. Alterations in the levels of various lipids in AD brains and dysregulation of lipid pathways and transportation have been implicated in AD pathogenesis. Clinically, evidence for a high-fat diet firmly links disrupted lipid metabolism to the pathogenesis and progression of AD, although contradictory findings warrant further exploration. In view of the significance of various lipids in brain physiology, the discovery of complex and diverse mechanisms that connect lipid metabolism with AD-related pathophysiology will bring new hope for patients with AD, underscoring the importance of lipid metabolism in AD pathophysiology, and promising targets for therapeutic intervention. Specifically, cholesterol, sphingolipids, and fatty acids have been shown to influence amyloid-beta (Aβ) accumulation and tau hyperphosphorylation, which are hallmarks of AD pathology. Recent studies have highlighted the potential therapeutic targets within lipid metabolism, such as enhancing apolipoprotein E lipidation, activating liver X receptors and retinoid X receptors, and modulating peroxisome proliferator-activated receptors. Ongoing clinical trials are investigating the efficacy of these strategies, including the use of ketogenic diets, statin therapy, and novel compounds like NE3107. The implications of these findings suggest that targeting lipid metabolism could offer new avenues for the treatment and management of AD. By concentrating on alterations in lipid metabolism within the central nervous system and their contribution to AD development, this review aims to shed light on novel research directions and treatment approaches for combating AD, offering hope for the development of more effective management strategies.

Altered Sphingolipid Hydrolase Activities and Alpha-Synuclein Level in Late-Onset Schizophrenia.

Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features of schizophrenia (SCZ) have been demonstrated in patients with several lysosomal storage disorders (LSDs). Taking into account the critical role of lysosomal function for neuronal cells' lysosomal dysfunction could be proposed in SCZ pathogenesis. The current study analyzed lysosomal enzyme activities and the alpha-synuclein level in the blood of patients with late-onset SCZ. In total, 52 SCZ patients with late-onset SCZ, 180 sporadic Parkinson's disease (sPD) patients, and 176 controls were recruited. The enzymatic activity of enzymes associated with mucopolysaccharidosis (alpha-L-Iduronidase (IDUA)), glycogenosis (acid alpha-glucosidase (GAA)) and sphingolipidosis (galactosylceramidase (GALC), glucocerebrosidase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase)) and concentration of lysosphingolipids (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), and lysosphingomyelin (LysoSM)) were measured using LC-MS/MS. The alpha-synuclein level was estimated in magnetically separated CD45+ blood cells using the enzyme-linked immunosorbent assay (ELISA). Additionally, NGS analysis of 11 LSDs genes was conducted in 21 early-onset SCZ patients and 23 controls using the gene panel PGRNseq-NDD. Decreased ASMase, increased GLA activities, and increased HexSpn, LysoGb3, and LysoSM concentrations along with an accumulation of the alpha-synuclein level were observed in late-onset SCZ patients in comparison to the controls (p < 0.05). Four rare deleterious variants among LSDs genes causing mucopolysaccharidosis type I (IDUA (rs532731688, rs74385837) and type III (HGSNAT (rs766835582)) and sphingolipidosis (metachromatic leukodystrophy (ARSA (rs201251634)) were identified in five patients from the group of early-onset SCZ patients but not in the controls. Our findings supported the role of sphingolipid metabolism in SCZ pathogenesis. Aberrant enzyme activities and compounds of sphingolipids associated with ceramide metabolism may lead to accumulation of alpha-synuclein and may be critical in SCZ pathogenesis.

Gut microbiota and liver metabolomics reveal the potential mechanism of Lactobacillus rhamnosus GG modulating the liver toxicity caused by polystyrene microplastics in mice.

Microplastics (MPs) are known to cause liver toxicity as they can spread through the food chain. Most researches on their toxicity have focused on individual organs, neglecting the crucial "gut-liver axis"-a bidirectional communication pathway between the gut and liver. Probiotics have shown promise in modulating the effects of environmental pollutants. In this study, we exposed mice to Lactobacillus rhamnosus GG (LGG, 100 mg/kg b.w./d) and/or polystyrene microplastics (PS-MPs, 5 mg/kg b.w./d) for 28 d via gavage to investigate how probiotics influence live toxicity through the gut-liver axis. Our results demonstrated that PS-MPs induced liver inflammation (increased IL-6 and TNF-α) and disrupted lipid metabolism. However, when combined with LGG, these effects were alleviated. LGG also improved colon health, rectifying ciliary defects and abnormal mucus secretion caused by PS-MPs. Furthermore, LGG improved gut microbiota dysbiosis induced by PS-MPs. Metabolomics and gene expression analysis (Cyp7a1 and Cyp7b1) indicated that LGG modulated bile acid metabolism. In summary, LGG appears to protect the liver by maintaining gut homeostasis, enhancing gut barrier integrity, and reducing the liver inflammation. These findings confirm the potential of LGG to modulate liver toxicity caused by PS-MPs through the gut-liver axis, offering insights into probiotics' application for environmental pollutant detoxification.

Combined exposure of MAHs and PAHs enhanced amino acid and lipid metabolism disruption in epithelium leading asthma risk

Monoaromatic hydrocarbons (MAHs) and polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants from industry, with multiple adverse effects on respiratory system. However, the underlying mechanisms of their mixture to induce asthma is still unclear. Here, we examined mixture of 8 MAHs, mixture of 16 PAHs and a total mixture (MIX) on human bronchial epithelial (16-HBE) cells. Exposure to MIX resulted in increased expressions of asthma alarm cytokines (TSLP, IL-25 and IL-33), indicating potential asthma risk. Exposure to MIX led to significant upregulation of transcriptional level of oxidative stress and inflammation biomarkers through aryl hydrocarbon receptor activation, including SOD-2, NQO-1, IL-1β, IL-6 and IL-8 with 3.1, 19.9, 3.5, 23.4, 18.7, 28.1-fold change, indicated asthma related epithelial cell lesions. A total of 25, 49 and 59 differential metabolites were identified in cells response to MAH, PAH and MIX exposure, respectively, and enrichment analysis demonstrated MIX exposure disturbing alanine, aspartate and glutamate metabolism, glutathione metabolism, methionine metabolism and sphingolipid metabolism, involved in antioxidative defense and inflammation response. Combined exposure of MAHs and PAHs may result in increased toxic risks, and provide evidence to asthma onset and deterioration.

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways.

Hexafluoropropylene oxide dimer acid (HFPO-DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 μg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 μM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1β, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.

Increased fatty acid synthesis and disturbed lipid metabolism in Neuro2a cells after repeated cocaine exposure: A preliminary study

Chronic use of cocaine prompts neurodegeneration and neuroinflammation. Lipids play pivotal roles in neuronal function and pathology. Although evidence correlates cocaine use with the alteration of lipid metabolism in blood and brain, the precise mechanism remains to be elucidated. In this study, we explore the effect of cocaine on neuronal fatty acid profiles in vitro. Neuro2a cells following seven days of repeated exposure to cocaine (0, 600, 800, 1000 μM) showed apoptosis-irrelevant cell death, dysregulated autophagy, activation of atypical endoplasmic reticulum stress response, increased saturated and unsaturated fatty acid synthesis, and disrupted lipid metabolism. These preliminary findings indicated the association between lipid metabolism and cocaine-induced neurotoxicity, which should be beneficial for understanding the neurotoxicity of cocaine.

Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis

Anxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.

Transcriptomic and metabolomic analyses reveal the antibacterial mechanism of Zanthoxylum bungeanum Maxim. Essential oil against GBS

Streptococcus agalactiae (Group B Streptococcus, GBS), is one of the primary pathogens causing bovine mastitis. It is also a major cause of invasive neonatal infections such as meningitis, pneumonia, and bacteremia. In this study, the antibacterial effect of Zantheoxylum bungeanum essential oil (ZBEO) against GBS was evaluated through determination of minimum inhibitory concentration (MIC) and microstructure observation. Additionally, an integrated analysis of transcriptomics and metabolomics was conducted after treatment with ZBEO. Results showed that ZBEO had a good inhibitory effect on GBS and significant effects on its transcription and metabolic levels. We found that ZBEO can disrupt the physiological metabolism of GBS by inhibiting peptidoglycan biosynthesis, disrupting lipid metabolism, limiting amino acid metabolism, inhibiting the tricarboxylic acid cycle, and inhibiting the pentose phosphate pathway. These findings provide a theoretical basis for ZBEO as a novel natural antibacterial agent against microbial infections.