Disturbances In Lipid Metabolism Research Articles

Hepatotoxic Effects of Gaseous Sulfur Dioxide (SO₂), Nitrogen Dioxide (NO₂), and Their Mixture on Sea Bass (Centropristis striata): Hematological, Biochemical and Genotoxic Studies

This study meticulously explores the intricate hepatotoxic effects stemming from acute exposure to gaseous sulfur dioxide (SO2), nitrogen dioxide (NO2), and their amalgamation on sea bass (Centropristis striata). Employing a comprehensive approach involving hematological, cytotoxic, and histochemical analyses, the research provides crucial insights into the potential adverse impacts of these pollutants on fish health. The examination specifically focuses on the effects of SO2+NO2 on hematological, histochemical, and serum biochemical parameters in Centropristis striata. Treatment groups, subjected to LC30, LC50, and LC90 acute exposure of gaseous SO2, NO2, and SO2+NO2, alongside a control group, underwent evaluation of parameters such as red and white blood cells, hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, total protein, albumin, serum creatinine, and blood urea. At the 96th hour, RBC values decreased, and WBC values increased in all experimental conditions compared to the control group (p>0.05). MCV and MCH increased with the concentration of gaseous pollutants and exposure time (p>0.05). Hematological parameter variations underscore disruptions in blood composition and immune responses. Simultaneously, alterations in serum biochemical parameters suggest potential impairments in liver and kidney functions, along with disturbances in lipid metabolism. Significant declines in albumin levels, indicating potential liver dysfunction or inflammation due to SO2 and NO2 exposures, were observed at all experimental conditions, while decreased globulin levels suggest immunosuppressive effects from combined pollutants. A substantial increase in the albumin/globulin ratio further signals an imbalance indicative of potential liver dysfunction or inflammation. Varied responses in liver enzyme levels (SGPT/ALT, SGOT/AST, ALP) underscore potential liver damage or injury (p< 0.05). These findings deepen our understanding of environmental impacts on aquatic ecosystems, emphasizing the need for ongoing efforts to ensure the health and sustainability of fish populations in polluted environments.

Effect of a weight loss diet with or without Spirulina supplementation on serum lipids and antioxidant capacity of overweight dogs

Obesity is a major health issue in dogs associated with disturbances in lipid metabolism and oxidative stress. Spirulina has been shown to have hypolipidemic and antioxidant effects in various animal species. No such data regarding dogs are available, however. The present study aimed to investigate the effect of a therapeutic high-protein, high-fiber weight loss diet, with or without Spirulina supplementation, on biochemical parameters of overweight dogs, with particular reference to serum lipids and plasma antioxidant capacity. Thirty-two dogs completed a double-blind randomized placebo-controlled trial in which they received either Spirulina (S) or placebo (P) tablets in a body weight-dependent amount for 12 weeks; at the same time, both groups were fed the same calorie-restricted diet. Dogs were weighed weekly and calorie restriction was adjusted accordingly to ensure a 1% body weight loss per week. Blood samples were collected at baseline (T0), after 6 weeks (T1), and after 12 weeks (T2). No difference in body weight loss (S: -11.9 ± 0.8%, P: -10.6 ± 0.8%, p = 0.229) was detected between groups at T2. After 6 weeks and an average weight loss of around 6% (S: -6.7 ± 0.6%, P: -5.9 ± 0.6, p = 0.276), significant reductions of serum total cholesterol, glucose, alkaline phosphatase, paraxonase-1 (all p < 0.0001) and gamma-glutamyltransferase (p < 0.018) were observed in both groups, regardless of supplementation. Plasma antioxidant capacity increased significantly in both groups at T2 (p = 0.0003). Serum triglycerides decreased significantly from T0 to T1 in the Spirulina group (p < 0.0001) but not in the placebo group (p = 0.28); as for the difference between groups, a non-significant trend (p = 0.098) was detected. A significantly higher percentage of dogs (p = 0.028) in the Spirulina group achieved a serum triglycerides reduction > 15% compared to baseline at T1 and > 30% at T2. A treatment effect (p = 0.0416) was found for bilirubin, which decreased only in the Spirulina group. In conclusion, a weight loss of around 6% achieved with a high-protein, high-fiber hypocaloric diet is sufficient to induce significant positive metabolic effects and improve lipid, glucose, and liver enzyme values. Plasma antioxidant capacity was tested in dogs undergoing a weight loss program for the first time, demonstrating that overweight individuals are in a deficient status and that a weight loss of around 10% is able to restore values comparable to those of healthy individuals. The results of this study suggest that Spirulina may manifest a hypotriglyceridemic effect in dogs, even if further research is needed to infer causation. The role Spirulina that supplementation plays in bilirubin metabolism and its related beneficial effect is also worth exploring.

Discovery of potential ferroptosis and osteoporosis biomarkers through TMT proteomics and bioinformatics analysis

BackgroundPrimary osteoporosis has increasingly emerged as a major issue affecting human health, with a complex specific pathogenic mechanism. As a research hotspot, ferroptosis plays a vital role in the pathogenesis of primary osteoporosis, aiming to explore the link and specific target genes between ferroptosis and primary osteoporosis.MethodsBy utilizing TMT proteomics and bioinformatics analyses, we elucidated the linkages and key targets of the ferroptosis pathway in an ovariectomized osteoporotic rat model. Forty 12-week-old SD female rats were employed in the study, of which 20 female SD rats were ovariectomized as the OVX group and 20 female SD rats were employed as the SHAM group. At the end of the experiments, the femurs of the rats were excised for computed tomography tests and used for hematoxylin and eosin staining. Finally, we extracted bone tissue proteins for TMT proteomics analysis and protein blotting verification.ResultsThe proteomics results of the VX and SHAM groups showed that 133 proteins were significantly changed, of which 91 proteins were upregulated and 42 proteins were downregulated, including TXN, TMSB4X, TFRC, TF, RELA, PARP14, CP, CAPG, and ADIPOQ. The expression of key proteins in the bone tissues was detected by protein blotting. The expression of TFR1, TFRC and TF was upregulated, whereas the expression of Cp, TXN and BMP-2 was downregulated.ConclusionsTMT proteomics and functional enrichment analyses in our study substantiated that in osteoporosis, disturbances in lipid metabolism lead to the emergence of oxidative stress with iron homeostasis imbalance.

Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance

Elevated concentrations of amino acids (AAs) are commonly observed in patients with nonalcoholic fatty liver disease (NAFLD). Individuals with hypopituitarism (HP) are at a heightened risk of developing NAFLD due to factors such as visceral obesity, increased insulin resistance (IR), and disturbances in lipid metabolism. However, the changes in AAs concentrations associated with HP remain poorly understood. Therefore, our study aimed to investigate whether individuals with HP, who were not receiving growth hormone replacement therapy (GHRT), exhibited altered AAs compared to controls (CTs), and whether these AAs were associated with IR, the presence of NAFLD, and the Metabolic Syndrome (MetS) score. The AAs profiles of 133 young males with HP (age: 24.5 ± 5.9; 57 with NAFLD and 76 without NAFLD) and 90 age and BMI-matched CTs were analyzed using untargeted metabolomics. The results revealed that most AAs were found to be elevated in subjects with HPs compared to CTs. Glutamate, glutamine, norleucine, and branched-chain amino acids (BCAAs) (leucine and valine) were correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), with glutamate and norleucine showing independent linkage. Glutamate and proline levels were specifically associated with MetS score, while alanine and proline linked to NAFLD. Given that elevated glutamate and BCAAs levels have higher prevalence of NAFLD, we hypothesized that the changes in AAs observed in HPs may be attributed to the impact of NAFLD and IR.

Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

Study on gut microbiota and metabolomics in postmenopausal women

Menopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16 s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis.

Diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints.

Early detection is warranted to improve prognosis of gastric cancer (GC) but remains challenging. Liquid biopsy combined with machine learning will provide new insights into diagnostic strategies of GC. Lipid metabolism reprogramming plays a crucial role in the initiation and development of tumors. Here, we integrated the lipidomics data of three cohorts (n = 944) to develop the lipid metabolic landscape of GC. We further constructed the serum lipid metabolic signature (SLMS) by machine learning, which showed great performance in distinguishing GC patients from healthy donors. Notably, the SLMS also held high efficacy in the diagnosis of early-stage GC. Besides, by performing unsupervised consensus clustering analysis on the lipid metabolic matrix of patients with GC, we generated the gastric cancer prognostic subtypes (GCPSs) with significantly different overall survival. Furthermore, the lipid metabolic disturbance in GC tissues was demonstrated by multi-omics analysis, which showed partially consistent with that in GC serums. Collectively, this study revealed an innovative strategy of liquid biopsy for the diagnosis of GC on the basis of the serum lipid metabolic fingerprints.

Impact of sleep problems on the cardiometabolic risks: an integrated epidemiological and metabolomics study

BackgroundWe investigated the association between sleep problems and cardiometabolic risks and the potential linking effect of metabolites and metabolic pathways based on multi-layered research, including observational, mendelian randomization (MR), and metabolomics analysis.MethodsA cross-sectional analysis of the 2015–2018 National Health and Nutrition Examination Survey (NHANES) dataset was conducted to identify the association between sleep problems and cardiometabolic risks. A subsequent MR study based on genetic data was performed to explore the causal correlation of significant associations in the NHANES study. The underlying alteration of metabolism was explored by constructing zebrafish models and wide-targeted metabolomics analysis.ResultsThe cross-sectional analysis of the NHANES database revealed a significant association of snoring with obesity [OR = 2.65, 95% confidence intervals (CI): 1.87, 3.74]; sleep apnea with hypertension (OR = 1.68, 95% CI: 1.14, 2.48) and obesity (OR = 1.44, 95% CI: 1.05, 1.96); trouble sleeping with hypertension (OR = 1.84, 95% CI: 1.18, 2.86), obesity (OR = 1.56, 95% CI: 1.07, 2.26), and type 2 diabetes (T2DM) (OR = 1.52, 95% CI: 1.02, 2.25). MR analysis verified the causal relationship between genetically proxied sleep apnea or snoring and obesity. The decreased activity levels and altered expression levels of six circadian genes (bmal1b, cry1aa, cry1ab, clock1a, per1b, per2) were identified in the zebrafish of the sleep disorder group. Multiple metabolites related to disturbed glucose metabolism (e.g., 20-HETE), lipid metabolism (e.g., inosine), and vascular-related metabolites (e.g., riboflavin) were finally identified, indicating the latent effect of metabolism.ConclusionsThis study identified the chain of sleep-circadian rhythm-metabolism-cardiometabolic risks. These findings can promote improved prevention implementation and therapeutic strategies.

The effects of laparoscopic sleeve gastrectomy on serum levels of growth hormone and insulin-like growth factor 1

Background. It is unclear exactly how bariatric surgery affects the body’s metabolic and physiological functions. The purpose of the study was to assess the activity of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in obese individuals before and six months after laparoscopic sleeve gastrectomy. Materials and methods. This study included 52 patients with a body mass index (BMI) ranging from 35 to 56 kg/m2 who qualified for laparoscopic sleeve gastrectomy and had completed data at the 6-month postoperative follow-up. All patients were clinically examined by a team of surgeons and a physician before operation. The serum levels of GH and IGF-1 were assessed pre- and post-operatively. Results. The study included 52 patients with obesity who were undergoing laparoscopic gastric sleeve surgery. Their mean age was 32.04 ± 6.90 years. More than half of the patients, 27 (51.9 %), were aged 19 to 32 years, 32 (61.5 %) patients were females, and 38 (73.1 %) had a BMI of 35–49.9 kg/m2. There was a significant increase in the serum GH after the sleeve gastrectomy compared to the pre-operative level (0.95 ± 0.30 vs 0.62 ± 0.40 ng/ml, p = 0.0001). IGF-1 also significantly increased after the surgery: 117.13 ± 32.40 vs 102.63 ± 33.90 ng/ml (p = 0.0001). Concerning BMI, there was no significant difference in the GH mean for patients with a BMI of 35–49.9 and 50–56 kg/m2 pre- and post-operatively: 0.6 vs 0.8 (p = 0.07) and 0.9 vs 1 (p = 0.5), respectively. On the other hand, IGF-1 exhibited a significant difference before and after surgery: 107.7 vs 88.9 ng/ml (p = 0.02) and 123.2 vs 100.7 (p = 0.03). Conclusions. This study concludes that sleeve gastrectomy significantly increases the serum level of both GH and IGF-1 and, consequently, their effects on disturbed lipid and protein metabolism in morbidly obese patients.

Ferroptosis as a Therapeutic Target in Neurodegenerative Diseases: Exploring the Mechanisms and Potential of Treating Alzheimer's Disease and Parkinson's Disease.

Amidst the rising global burden of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, there is an urgent need for novel therapeutic strategies to combat these debilitating conditions. These diseases are characterized by progressive neural dysfunction leading to cognitive impairments, for which current therapeutic strategies remain palliative at best. Recently, the discovery of ferroptosis, a novel cell death mode that is different from apoptosis and autophagy, has opened new avenues in the field of cognitive research. With in-depth research on ferroptosis, the clinical significance of iron homeostasis disorders and lipid peroxidation in the occurrence, development, and treatment of neurodegenerative diseases are gradually becoming apparent. This study aims to elucidate the roles of ferroptosis in the context of neurodegeneration and to explore its potential as a therapeutic target. By unraveling the intricate relationship between iron homeostasis disorders, oxidative damage, and lipid metabolism disturbances in these diseases, new intervention targets are revealed. It offers a new dimension to the management of neurocognitive impairments in Alzheimer's and Parkinson's diseases. The implications of these findings extend beyond just Alzheimer's and Parkinson's diseases. They also have relevance with other neurological conditions characterized by oxidative stress and iron dysregulation. This review contributes to increased knowledge of ferroptosis and provides a foundational understanding that could lead to the development of innovative therapeutic strategies. Ultimately, it may alleviate the development of neurodegenerative diseases and improve cognitive function by preventing ferroptosis, which has not only academic significance but also potential clinical significance.

Identification of key genes in diabetic nephropathy based on lipid metabolism.

Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes with a high incidence rate. Notably, the disturbance of lipid metabolism is associated with DN progression. The present study aimed to identify lipid metabolism-related hub genes associated with DN for improved diagnosis of DN. The gene expression profile data of DN and healthy samples (GSE142153) were obtained from the Gene Expression Omnibus database, and the lipid metabolism-related genes were obtained from the Molecular Signatures Database. Differentially expressed genes (DEGs) between DN and healthy samples were analyzed. The weighted gene co-expression network analysis (WGCNA) was performed to examine the relationship between genes and clinical traits to identify the key module genes associated with DN. Next, the Venn Diagram R package was used to identify the lipid metabolism-related genes associated with DN and their protein-protein interaction (PPI) network was constructed. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The hub genes were identified using machine-learning algorithms. The Gene Set Enrichment Analysis (GSEA) was used to analyze the functions of the hub genes. The present study also investigated the immune infiltration discrepancies between DN and healthy samples, and assessed the correlation between the immune cells and hub genes. Finally, the expression levels of key genes were verified by reverse transcription-quantitative (RT-q)PCR. The present study determined 1,445 DEGs in DN samples. In addition, 694 DN-related genes in MEyellow and MEturquoise modules were identified by WGCNA. Next, the Venn Diagram R package was used to identify 17 lipid metabolism-related genes and to construct a PPI network. GO analysis revealed that these 17 genes were markedly associated with 'phospholipid biosynthetic process' and 'cholesterol biosynthetic process', while the KEGG analysis showed that they were enriched in 'glycerophospholipid metabolism' and 'fatty acid degradation'. In addition, SAMD8 and CYP51A1 were identified through the intersections of two machine-learning algorithms. The results of GSEA revealed that the 'mitochondrial matrix' and 'GTPase activity' were the markedly enriched GO terms in both SAMD8 and CYP51A1. Their KEGG pathways were mainly concentrated in the 'pathways of neurodegeneration-multiple diseases'. Immune infiltration analysis showed that nine types of immune cells had different expression levels in DN (diseased) and healthy samples. Notably, SAMD8 and CYP51A1 were both markedly associated with activated B cells and effector memory CD8 T cells. Finally, RT-qPCR confirmed the high expression of SAMD8 and CYP51A1 in DN. In conclusion, lipid metabolism-related genes SAMD8 and CYP51A1 may play key roles in DN. The present study provides fundamental information on lipid metabolism that may aid the diagnosis and treatment of DN.

Environmental Heavy Metal Exposure and Associated Cardiovascular Diseases in Light of the Triglyceride Glucose Index.

Cardiovascular diseases (CVD), primarily ischemic heart disease and stroke, remain leading global health burdens. Environmental risk factors have a major role in the development of CVD, particularly exposure to heavy metals. The Triglyceride Glucose Index (TyG), a measure of insulin resistance and CVD risk, is the primary focus of this study, which summarizes the most recent findings on the effects of lead (Pb), arsenic (As), and cadmium (Cd) on CVD risk. A higher risk of CVD is correlated with an elevated TyG index, which has been linked to insulin resistance. Exposure to Cd is associated with disturbance of lipid metabolism and oxidative stress, which increases the risk of CVD and TyG. Exposure reduces insulin secretion and signaling, which raises the TyG index and causes dyslipidemia. Pb exposure increases the risk of CVD and TyG index via causing oxidative stress and pancreatic β-cell destruction. These results highlight the need of reducing heavy metal exposure by lifestyle and environmental modifications in order to lower the risk of CVD. To comprehend the mechanisms and create practical management plans for health hazards associated with heavy metals, more study is required.

Association analyses of nutritional markers with Parkinson’s disease and Alzheimer’s disease

IntroductionParkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative diseases with multifaceted etiology. Nutritional and metabolic abnormalities are frequently implicated in PD and AD. In this observational study, we analyzed a series of nutritional markers, and aimed to understand their association with AD and PD risk. MethodsA total of 424 PD patients, 314 AD patients, and 388 healthy controls were included. Nutritional markers including Hemoglobin A1c, vitamin B12, folate, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, total cholesterol (TC), uric acid and homocysteine (HCY) were measured. Significance for odds ratios examining was P < 0.0045 after bonferroni correction. ResultsMultifactor risk analysis showed that ApoB, LDL, and TC reduce PD risk, while HCY increase PD risk. ApoA1 and HCY are protective and risk factors for AD, respectively. ConclusionThe cross-sectional study demonstrates that HCY and lipid metabolism markers are associated with PD and AD risks. Our findings support the involvement of one-carbon metabolism and lipid metabolism disturbance in PD and AD.

Comparative study of blood glucose and glycated hemoglobin in type 2 diabetics in Lubumbashi city

Introduction: Diabetes mellitus is a complex disease, with polymorphic clinical expression and diverse etiopathogenesis, creating an absolute (insufficiency of secretion) or relative (resistance, etc.) defect in insulin effect. This defect in insulin secretion and/or action leads to chronic hyperglycemia with disturbances in carbohydrate, lipid and protein metabolism. Objective: The objective of our study was to establish the relationship between variations in blood sugar and glycated hemoglobin (HbA1c) in type 2 diabetics in Lubumbashi city. Methods: The study involved a sample of 39 known type 2 diabetics treated at the University Clinics of Lubumbashi. Venous blood samples were taken from all patients for the measurement of blood glucose after the 1st, 2nd and 3rd month of antidiabetic treatment and for the measurement of HbA1c after the 3rd month of treatment. Results: The average blood glucose concentrations obtained after the 1st, 2nd and 3rd month of treatment were respectively 180.28 ± 51.09 mg/dl ; 154.20 ± 49.33mg/dl and 135.58 ± 36.45 mg/dl while the percentage of HbA1c after the 3rd month of treatment was 5.90 ± 0.55. Statistical analysis showed that the average blood glucose obtained after the 1st month of treatment was significantly higher (P&lt;0.05) than those obtained after the 2nd and 3rd months of treatment. There was no significant difference between the average blood glucose obtained after the 2nd month of treatment and that obtained after the 3rd month of treatment. Furthermore, a positive correlation (r=0.56) was found between average blood glucose and HbA1c. Conclusion: On the one hand, our results show that the antidiabetic treatment followed by the patients was effective and, on the other hand, they highlight the need to associate the measurement of blood glucose with that of HbA1c in the diagnosis and treatment monitoring in diabetic patients.

Untargeted metabolomic analysis reveals a time-course hepatic metabolism disorder induced by short-term 6PPD exposure in rats

The tire antioxidant 6PPD has garnered extensive attention due to its widespread presence in the environment and the harmful effects of its transformation products on aquatic organisms. 6PPD has been detected in airborne dust, and it can enter mammals through inhalation exposure. While the toxic effects of 6PPD exposure have been reported in mammals, its effects on hepatic metabolism still remain poorly understood. Here, we collected the serum and liver samples at 1, 6, and 72 h following a single oral exposure of 100 mg/kg body weight (bw) 6PPD, respectively. We also investigated changes in serum and hepatic physiological indicators and metabolites, correspondingly. Results indicated that single time oral exposure a high dose of 6PPD did not significantly affect the physiological indexes of rats within a short time frame. However, untargeted metabolomics analysis of the metabolites in the liver at 1, 6, and 72 h revealed that the number of differential expression metabolites gradually increased over time and the most affected substances were lipids and lipid-like molecules. Interestingly, the KEGG pathway enrichment analysis indicated that 6PPD disrupted the riboflavin metabolism, leading to a significant decrease in FMN levels at all time points. In addition, the hepatic glucose metabolism was significantly affected at 6 and 72 h after oral administration. Taken together, short-term exposure to 6PPD disturbed lipid and riboflavin metabolism and gradually affected glucose metabolism in the liver of rats. These findings revealed the impacts of 6PPD on the hepatic metabolism in animals, and also offered some important insights into its toxicology and health risk.

Inflammatory and Lipid Biomarkers in Early Atherosclerosis: A Comprehensive Analysis

Introduction: Atherosclerosis is a leading cause of cardiovascular disease, characterized by lipid accumulation and chronic inflammation within arterial walls. Early detection in young adults is crucial for preventing adverse cardiovascular events. This study investigates the associations between inflammatory indices, lipid biomarkers, and the presence of atherosclerosis in patients aged 18 to 55 years. Methods: A cross-sectional study was conducted involving 89 participants divided into two groups: 62 patients with documented atherosclerosis (main group) and 27 healthy controls without significant atherosclerosis. Comprehensive data—including demographic information, medication use, imaging results, laboratory parameters, and calculated inflammatory indices (SIRI, SII, AISI, NLR, PLR, MLR)—were collected. Statistical analyses included correlation assessments, group comparisons using the Mann–Whitney U test, logistic regression modeling, feature importance analysis with Random Forest and Gradient Boosting classifiers, receiver operating characteristic (ROC) curves, and K-means clustering. Results: Significant differences were observed between the main and control groups. Patients with atherosclerosis exhibited elevated inflammatory indices (SIRI, NLR, MLR, SII) and lipid profile abnormalities (higher TC and LDL-C, lower HDL-C). Lp(a) and ANGPTL3 levels were significantly higher in the main group (p &lt; 0.001 and p &lt; 0.01, respectively). Logistic regression identified SIRI and ANGPTL3 as significant predictors of atherosclerosis, with the model demonstrating high accuracy (77%) and sensitivity (93%). Feature importance analysis confirmed the significance of SIRI and ANGPTL3, alongside traditional lipid biomarkers, in predicting disease presence. ROC analysis showed excellent model performance (AUC &gt; 0.80). Clustering analysis revealed two distinct patient subgroups characterized by predominant inflammatory profiles or lipid metabolism disturbances. Conclusions: Systemic inflammation and lipid abnormalities play significant roles in early atherosclerosis among young adults. Elevated SIRI and ANGPTL3 levels are potent predictors of disease presence. The integration of inflammatory indices and lipid biomarkers into predictive models enhances risk stratification and supports personalized medicine approaches.

The Role of Human Adiponectin Receptor 1 in 2-Ethylhexyl Diphenyl Phosphate Induced Lipid Metabolic Disruption.

Epidemiological evidence links exposure to 2-ethylhexyl diphenyl phosphate (EHDPP) with lipid metabolic disruption, typically attributed to nuclear receptors, while the role of membrane receptors remains underexplored. This study explored the role of adiponectin receptor 1 (AdipoR1) in EHDPP-induced lipid metabolic disturbances. We examined EHDPP's binding affinity and transcriptional impact on AdipoR1. AdipoR1 knockdown (AdipoR1kd) human liver cells and coculture experiments with AdipoR1 activator (AdipoRon) were used to investigate the effect and the mechanism. EHDPP disrupted triglyceride and phospholipid synthesis and altered corresponding gene expression, mirroring effects in AdipoR1kd cells but diminishing in EHDPP-treated AdipoR1kd cells. RNA sequencing revealed that EHDPP primarily disrupted oxidative phosphorylation and insulin signaling dependent on AdipoR1. Mechanistically, EHDPP interacted with AdipoR1 and reduced AdipoR1 protein levels at 10-7 mol/L or higher, weakening the activation of the calmodulin dependent protein kinase β (CaMKKβ)/AMPK/acetyl CoA carboxylase pathway. Furthermore, EHDPP pretreatment blocked the increase in Ca2+ flux and the corresponding kinase CaMKKβ, as well as liver kinase B1 (LKB1) activation induced by AdipoRon, which is necessary for AMPK activation. Collectively, these findings demonstrate that EHDPP-induced lipid imbalance is partially dependent on AdipoR1, expanding the understanding of environmental metabolic disruptors beyond nuclear receptors.

Associations of dietary total, heme, non-heme iron intake with diabetes, CVD, and all-cause mortality in men and women with diabetes

BackgroundIron metabolism disorders significantly increase the risk of diabetes and its related complications by inducing oxidative stress, inflammation, insulin resistance, and disturbances in glucose and lipid metabolism. However, whether dietary iron intake can influence progression of diabetes remains unclear. The present study aims to investigate the relationship between total iron, heme iron, and non-heme iron intake and diabetes, CVD, and all-cause mortality among men and women with diabetes in the U.S. population. MethodsA total of 4416 adults with diabetes(2415 men and 2001 women) from the NHANES 2003–2014 were enrolled. Dietary information was collected by 24-h dietary recall during two nonconsecutive days. Dietary total iron intake was measured based on the dietary survey. Dietary heme iron intake was calculated based on its proportion in dietary total iron intake from each food. non-heme iron is the difference between total iron and heme iron. Diabetes, CVD, and all-cause mortality status were identified as main outcomes. Cox models and RCS analysis were performed to estimate the hazard ratios and 95%CIs. ResultsFor men, the participants with a higher dietary heme iron intake were associated with higher risks of CVD (HRheme iron = 1.61,95%CI:1.03–2.51) and all-cause mortality (HRheme iron = 1.42,95%CI:1.10–1.83). For women, participants in the highest quartile of dietary total/heme/non-heme iron intake had a higher diabetes mortality risk ((HRtotal iron = 2.33,95%CI:1.24–4.38; HRheme iron = 1.87,95%CI:1.00–3.49; HRnon-heme iron = 2.28,95%CI:1.19–4.39), compared to those in the lowest quartile. Additionally, the dose–response curve for the relationship between dietary non-heme iron intake and CVD mortality followed a reverse J-shape in women with diabetes. ConclusionsHigher dietary heme iron intake was associated with an increased CVD mortality risk in both men and women with diabetes. Additionally, higher dietary total, heme, and non-heme iron intake was linked to an increased risk of diabetes mortality among women with diabetes. Therefore, women with diabetes should pay more attention on the overconsumption of any type of dietary iron.

Sodium Hypochlorite (NaClO) Disturbed Lipid Metabolism in Larval Zebrafish (Danio rerio), as Revealed by Lipidomics and Transcriptomics Analyses.

Sodium hypochlorite (NaClO) has been widely utilized since the initial outbreak of coronavirus disease (COVID-19). The widespread use of NaClO means that it can directly enter aquatic ecosystems through wastewater discharge. In this study, we analyzed the expression of PPAR-γ, FAS, and ACC1, which significantly increased in larval zebrafish following exposure to 300 μg/L NaClO for 7 days. Additionally, we examined the effects of high concentrations of NaClO on zebrafish through non-targeted lipidomics and transcriptomics. A total of 44 characteristic lipid molecules were identified using non-targeted lipidomics; an absolute quantitative analysis revealed that the contents of these subclasses of lipids decreased significantly following exposure to 300 μg/L NaClO for 7 days. The levels of triglyceride (TG), phosphatidylethanolamines (PE), and diglyceride (DG) were particularly affected. Transcriptomic analysis revealed that exposure to 300 μg/L NaClO could significantly disrupt global gene transcription in larval zebrafish. Interestingly, more than 700 differentially expressed genes (DEGs) were identified, primarily associated with lipid metabolism and glycometabolism pathways. Overall, our study provided new insights into the toxicological effects of chlorine-containing disinfectants in aquatic organisms.

Comparative analysis of transcriptomics and metabolomics provides insights into the mechanisms of VPAHPND invasion and hepatopancreatic damage in Litopenaeus vannamei

Acute hepatopancreatic necrosis disease (AHPND) poses significant threats to the global shrimp farming industry; however, its molecular mechanisms remain largely unknown. Previous research has primarily focused on comparisons between infected and non-infected states, limiting our understanding of VPAHPND mechanisms. We integrated transcriptomic and metabolomic analyses to investigate the pathogenic mechanism underpinning AHPND in highly vulnerable post-larvae (PL) stage shrimp. By comparing shrimp infected with VPAHPND, those infected with non-VPAHPND, and uninfected shrimp (controls), we identified different VPAHPND infection responses, including significant cytoskeleton and metabolic reprogramming changes. Specifically, VPAHPND infection disturbed lipid, glutathione, and bile acid metabolism, while a key regulatory factor Farnesoid X Receptor (FXR) in these pathways was down-regulated. These findings suggest that VPAHPND manipulates host metabolism to enhance infectivity, leading to severe and irreparable hepatopancreas damage. Our study highlights the molecular interactions between VPAHPND and shrimp, and provides potential targets to mitigate the impact of AHPND in aquaculture.