Associations of Cardiometabolic Indices With Peptides Related to Hypertensive Disorders of Pregnancy in Adult Men.

BACKGROUND: Seven peptides with low molecular weights in blood have been identified as possible biomarkers of hypertensive disorders of pregnancy (HDP). A history of HDP is known to be associated with a high risk of cardiovascular disease in the later life of women with HDP. However, it remains to be determined whether HDP-related peptides are useful biomarkers of cardiovascular disease in the general population. The purpose of this study was to determine the relationships between these peptides and cardiometabolic risk in adult men. METHODS: We investigated the relationships between HDP-related peptides and two recent indices of cardiometabolic risk, hematometabolic index (HMI) and lipid accumulation product (LAP), in male workers aged 35 to 69 years. Concentrations of the HDP-related seven peptides with mass/charge ratios (m/z) of 2081 (P-2081), 2091 (P-2091), 2127 (P-2127), 2209 (P-2209), 2378 (P-2378), 2858 (P-2858), and 3156 (P-3156) were measured simultaneously by using a mass spectrometer. Standardized partial regression coefficients (ß) were obtained in multivariable linear regression analysis, and mean levels of the log-transformed HMI and LAP were compared in tertile groups of each peptide in the analysis of covariance with adjustment for age, habits of smoking and alcohol drinking, history of diabetes, and medication therapy for dyslipidemia. RESULTS: There was a significant positive correlation between the HMI and the serum level of P-2378 (ß = 0.310), a fragment of complement component 4, while a significant inverse correlation (ß = -0.389) was obtained between the LAP and the serum level of P-3156, a fragment of inter-α-trypsin inhibitor heavy chain H4. Other peptides (P-2081, P-2091, P-2127, P-2209, and P-2858) did not show significant correlations with the HMI or LAP. The log-transformed HMI tended to be higher with an increase in the tertile for P-2378. The mean level of log-transformed LAP in the first tertile group of P-3156 was significantly higher than those in the second and third tertile groups of P-3156. CONCLUSION: The HDP-related peptides with m/z of 2378 and m/z of 3156 were shown to be associated with the HMI and LAP, respectively, which are recent indices reflecting cardiometabolic risk. Therefore, the peptides with m/z of 2378 and m/z of 3156 were thought to be potential biomarkers for discrimination of cardiovascular risk in adult men. Further studies on the relationships between the peptides and cardiovascular risk factors in non-pregnant women are needed to confirm the findings of this study.

LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Evaluation of the ability of insulin resistance and lipid-related indices to predict the presence of NAFLD in obese adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become an important health issue in adolescents. Although several parameters and indices have been investigated for the evaluation of NAFLD in adults, these indices are limited in adolescents. In this study, body mass index, waist circumference, triponderal mass index, HbA1c, homeostatic model assessment insulin resistance (HOMA-IR), triglyceride/high-density lipoprotein (Tg/HDL), the lipid accumulation product (LAP) index, the triglyceride-glucose (TyG) index and the aminotransferase (AT) index were examined together, and their diagnostic values in the clinical treatment of NAFLD were compared. MATERIALS AND METHODS: Seventynine adolescents (10-19 years old) with obesity who were admitted to a pediatric clinic between January and August 2022 and who were diagnosed with exogenous obesity without any comorbidities were included in the study. The presence of NAFLD was evaluated by liver magnetic resonance imaging. The laboratory findings were obtained retrospectively from system records. Parameters were compared between the NAFLD (+) and NAFLD (-) groups. Logistic regression analysis was used to determine the most effective factors for NAFLD treatment. Receiver operating characteristic (ROC) analysis was performed with significant indices. Sex, HOMA-IR, TyG and AT indices were evaluated together with multivariate analysis to design a diagnostic scale. RESULTS: HbA1c, HOMA-IR, AT indices and TyG indices were greater in the NAFLD (+) group (P = 0.012; P = 0.001; P = 0.012; P = 0.002, respectively). There was a positive correlation between liver fat percentage and HOMA-IR, the TyG index, the AT index, and Tg/HDL. According to the regression analysis, male sex and elevated HOMA-IR were determined to be significant risk factors for the presence of NAFLD. A probability scale with 4 parameters [sex, HOMA-IR, the TyG index, and alanine aminotransferase (ALT)] was designed with 82.5% specificity and 80% sensitivity. CONCLUSION: Evaluation of the HOMA-IR and TyG indices, especially in high-risk patients, will support the diagnosis of NAFLD via ultrasonography. A probability scale with ALT, HOMA-IR, TyG, and sex data with a diagnostic accuracy of 80% may aid in the diagnosis of NAFLD in adolescents with obesity.

Effect of hydroxy-α-sanshool on lipid metabolism in liver and hepatocytes based on AMPK signaling pathway.

BACKGROUND: With the increasing awareness of the safety of traditional Chinese medicine and food, as well as in-depth studies on the pharmacological activity and toxicity of Zanthoxylum armatum DC. (ZADC), it has been found that ZADC is hepatotoxic. However, the toxic substance basis and mechanism of action have not been fully elucidated. Hydroxy-α-sanshool (HAS) belongs to an amide compound in the fruits of ZADC, which may be hepatotoxic. However, the specific effects of HAS, including liver toxicity, are unclear. PURPOSE: The objectives of this research was to determine how HAS affects hepatic lipid metabolism, identify the mechanism underlying the accumulation of liver lipids by HAS, and offer assurances on the safe administration of HAS. METHODS: An in vivo experiment was performed by gavaging C57 BL/6 J mice with various dosages of HAS (5, 10, and 20 mg/kg). Biochemical indexes were measured, and histological analysis was performed to evaluate HAS hepatotoxicity. Hepatic lipid levels were determined using lipid indices and oil red O (ORO) staining. Intracellular lipid content were determined by biochemical analyses and ORO staining after treating HepG2 cells with different concentrations of HAS in vitro. Mitochondrial membrane potential, respiratory chain complex enzymes, and ATP levels were assessed by fluorescence labeling of mitochondria. The levels of proteins involved in lipogenesis and catabolism were determined using Western blotting. RESULTS: Mice in the HAS group had elevated alanine and aspartate aminotransferase blood levels as well as increased liver index compared with the controls. The pathological findings showed hepatocellular necrosis. Serum and liver levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were increased, whereas high-density lipoprotein cholesterol levels decreased. The ORO staining findings demonstrated elevated liver lipid levels. In vitro experiments demonstrated a notable elevation in triglyceride and total cholesterol levels in the HAS group. ATP, respiratory chain complex enzyme gene expression, mitochondrial membrane potential, and mitochondrial number were reduced in the HAS group. The levels of lipid synthesis-associated proteins (ACC, FASN, and SREBP-1c) were increased, and lipid catabolism-associated protein levels (PPARα and CPT1) and the p-AMPK/AMPK ratio were decreased in vivo and in vitro. CONCLUSION: HAS has hepatotoxic effects, which can induce fatty acid synthesis and mitochondrial function damage by inhibiting the AMPK signaling pathway, resulting in aberrant lipid increases.

Association between indicators of visceral lipid accumulation and infertility: a cross-sectional study based on U.S. women.

BACKGROUND: Evidence on the association between visceral lipid accumulation and infertility remains limited and controversial. Therefore, the current investigation is the first investigation to unveil this correlation by utilizing novel indicators of visceral lipid accumulation. METHODS: The present study utilized the NHANES 2013-2020 dataset. Researchers utilized multiple logistic regression, smoothed curve fitting, and subgroup analysis to investigate the associations of waist circumference (WC), metabolic score for visceral fat (METS-VF), lipid accumulation product (LAP), visceral adiposity index (VAI) with infertility. Additionally, the eXtreme Gradient Boosting (XGBoost) algorithm model was utilized to evaluate the relative importance of the factors. RESULTS: After adjusting for potential factors that could influence the results, researchers discovered that all these four indicators of visceral lipid accumulation exhibited strong positive correlations with the probability of infertility. The subgroup analysis demonstrated that the correlations remained consistent in the majority of subgroups (P for interaction > 0.05). The results of XGBoost algorithm model indicate that METS-VF is the most meaningful factor in infertility. The ROC curve research revealed that while METS-VF had the greatest AUC values, there was no variation in the AUC value of different markers of visceral fat accumulation (P > 0.05). CONCLUSIONS: The present investigation discovered that increased WC, METS-VF, LAP, and VAI were associated with a heightened prevalence of infertility.

Prediction of the 10-year incidence of type 2 diabetes mellitus based on advanced anthropometric indices using machine learning methods in the Iranian population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing chronic disease that can lead to disability and early death. This study aimed to establish a predictive model for the 10-year incidence of T2DM based on novel anthropometric indices. METHODS: This was a prospective cohort study comparing people with (n = 1256) and without (n = 5193) diabetes mellitus in phase II of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. The association of several anthropometric indices in phase I, including Body Mass Index (BMI), Body Adiposity Index (BAI), Abdominal Volume Index (AVI), Visceral Adiposity Index (VAI), Weight-Adjusted-Waist Index (WWI), Body Roundness Index (BRI), Body Surface Area (BSA), Conicity Index (C-Index) and Lipid Accumulation Product (LAP) with T2DM incidence (in phase II) were examined; using Logistic Regression (LR) and Decision Tree (DT) analysis. RESULTS: BMI followed by VAI and LAP were the best predictors of T2DM incidence. Participants with BMI < 21.25 kg/m2 and VAI ≤ 5.9 had a lower chance of diabetes than those with higher BMI and VAI levels (0.033 vs. 0.967 incident rate). For BMI > 25 kg/m2, the chance of diabetes rapidly increased (OR = 2.27). CONCLUSIONS: BMI, VAI, and LAP were the best predictors of T2DM incidence.

Insulin resistance may accelerate typical changes in heart function among type 1 diabetes patients, particularly in overweight patients: a preliminary study.

Introduction: Type 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D. Methods: Adult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography. Results: The mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m2. Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities. Conclusions: IR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup.

Gender-specific accuracy of lipid accumulation product index for the screening of metabolic syndrome in general adults: a meta-analysis and comparative analysis with other adiposity indicators.

BACKGROUND: Lipid accumulation product (LAP) is a novel predictor index of central lipid accumulation associated with metabolic and cardiovascular diseases. This study aims to investigate the accuracy of LAP for the screening of metabolic syndrome (MetS) in general adult males and females and its comparison with other lipid-related indicators. METHODS: A systematic literature search was conducted in PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ProQuest for eligible studies up to May 8, 2024. Outcomes were pooled mean difference (MD), odds ratio (OR), and diagnostic accuracy parameters (sensitivity, specificity, and area under the summary receiver operating characteristic [AUSROC] curve). Comparative analysis was conducted using Z-test. RESULTS: Forty-three studies involving 202,313 participants (98,164 males and 104,149 females) were included. Pooled MD analysis showed that LAP was 45.92 (P < 0.001) and 41.70 units (P < 0.001) higher in men and women with MetS, respectively. LAP was also significantly associated with MetS, with pooled ORs of 1.07 (P < 0.001) in men and 1.08 (P < 0.001) in women. In men, LAP could detect MetS with a pooled sensitivity of 85% (95% CI: 82%-87%), specificity of 81% (95% CI: 80%-83%), and AUSROC curve of 0.88 (95% CI: 0.85-0.90), while in women, LAP had a sensitivity of 83% (95% CI: 80%-86%), specificity of 80% (95% CI: 78%-82%), and AUSROC curve of 0.88 (95% CI: 0.85-0.91). LAP had a significantly higher AUSROC curve (P < 0.05) for detecting MetS compared to body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), body roundness index (BRI), a body shape index (ABSI), body adiposity index (BAI), conicity index (CI) in both genders, and waist circumference (WC) and abdominal volume index (AVI) in females. CONCLUSION: LAP may serve as a simple, cost-effective, and more accurate screening tool for MetS in general adult male and female populations.

Comprehensive pharmacological and experimental study of Ginsenoside Re as a potential therapeutic agent for non-alcoholic fatty liver disease.

OBJECTIVE: Ginsenoside Re, a unique tetracyclic triterpenoid compound found in ginseng, has been suggested in previous reports to improve non-alcoholic fatty liver disease (NAFLD) by modulating lipid imbalance. This study aims to elucidate the potential mechanisms of Ginsenoside Re in treating NAFLD through a combination of bioinformatics analysis and biological experiments. METHODS: Network pharmacology methods were employed to systematically depict the effective components and mechanisms of Ginsenoside Re in improving NAFLD. Molecular docking was utilized to evaluate the binding affinity of Ginsenoside Re with NAFLD-related targets and identify potential targets. NAFLD-related target genes were obtained from the GEO database for gene enrichment analysis, revealing signaling pathways, biological processes, and gene differential expression. Finally, animal experiments were conducted to verify the mechanism of action of Ginsenoside Re in NAFLD. RESULTS: Network pharmacology analysis revealed that Ginsenoside Re improves NAFLD by modulating targets such as AKT1 and TLR4, findings corroborated by molecular docking, GEO database analysis, and experimental validation. Further investigation found that Ginsenoside Re ameliorates lipid metabolism disorders and inflammatory responses induced by NAFLD by modulating the PI3K/AKT and TLR4/NF-κB signaling pathways. CONCLUSION: Our study demonstrates the pharmacological effects of Ginsenoside Re in treating NAFLD, implicating multiple components, targets, and pathways. This provides a solid foundation for considering Ginsenoside Re as an alternative therapy for NAFLD, with promising clinical applications.

The association between dietary inflammatory index with some cardio-metabolic risk indices among the patients with type 2 diabetes from Hoveyzeh cohort study: a cross-sectional study.

BACKGROUND: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. METHODS: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. RESULTS: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). CONCLUSION: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications.

TNFAIP1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the LEENE/FoxO1/ABCA1 pathway.

Macrophage lipid accumulation is a critical contributor to foam cell formation and atherosclerosis. Tumor necrosis factor-α-induced protein 1 (TNFAIP1) is closely associated with cardiovascular disease. However, its role and molecular mechanisms in atherogenesis remain unclear. TNFAIP1 was knocked down in THP-1 macrophage-derived foam cells and apolipoprotein-deficient (apoE-/-) mice using lentiviral vector. The expression of lncRNA enhancing endothelial nitric oxide synthase expression (LEENE), Forkhead box O1 (FoxO1) and ATP binding cassette transporter A1 (ABCA1) was evaluated by qRT-PCR and/or western blot. Lipid accumulation in macrophage was assessed by high-performance liquid chromatography and Oil red O staining. RNA immunoprecipitation and RNA pull-down assay were performed to verify the interaction between LEENE and FoxO1 protein. Atherosclerotic lesions were analyzed using HE, Oil red O and Masson staining. Our results showed that TNFAIP1 was significantly increased in THP-1 macrophages loaded with oxidized low-density lipoprotein. Knockdown of TNFAIP1 enhanced LEENE expression, promoted the direct interaction of LEENE with FoxO1 protein, stimulated FoxO1 protein degradation through the proteasome pathway, induced ABCA1 transcription, and finally suppressed lipid accumulation in THP-1 macrophage-derived foam cells. TNFAIP1 knockdown also up-regulated ABCA1 expression, improved plasma lipid profiles, enhanced the efficiency of reverse cholesterol transport and attenuated lesion area in apoE-/- mice. Taken together, these results provide the first direct evidence that TNFAIP1 aggravates atherosclerosis by promoting macrophage lipid accumulation via the LEENE/FoxO1/ABCA1 signaling pathway. TNFAIP1 may represent a promising therapeutic target for atherosclerotic cardiovascular disease.

Discovery of natural AMPK activator from the fruits of Xanthium sibiricum Patr.: Xanthiumine A, protoberberine alkaloid with unique C28 skeleton.

Two protoberberine alkaloids with a unique C28 skeleton, named xanthiumines A (1) and B (2), respectively, were isolated from the fruits of Xanthium sibiricum Patr. Their structures including absolute configurations were unequivocally established by the comprehensive NMR and MS spectroscopic data analysis together with gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are the first examples of natural protoberberine alkaloid with a phenolic acid group at C-13a. Their plausible biosynthetic pathway was proposed on the basis of the coexisting alkaloid monomer as the precursor. Furthermore, the effects and related molecular mechanism of compound 1 on hepatic lipid accumulation were also investigated in oleic acid (OA)-treated HepG2 cells.

Association between lipid accumulation product index and chronic kidney disease: A systematic review and meta-analysis.

Diabetes mellitus and lipid metabolism disorders are increasingly recognized as key contributors to the development of chronic kidney disease (CKD). The lipid accumulation product (LAP) index, a novel marker of lipid accumulation, has potential implications for CKD risk assessment. The present meta-analysis aimed to assess the association between LAP index and CKD, with an emphasis on varying impacts in diabetic and non-diabetic populations. A comprehensive search for relevant publications was performed using PubMed/MEDLINE, Scopus, Cochrane Library, ScienceDirect and Google Scholar databases, and a meta-analysis of 17 studies was performed to investigate the relationship between LAP index and CKD. The random-effects inverse-variance model employing the DerSimonian-Laird estimator for τ² was utilized to calculate pooled odds ratios (ORs). Diagnostic accuracy was assessed using summary receiver operating characteristic (ROC) curves, with calculations of the area under the ROC curve (AUROC), sensitivity, specificity, likelihood ratios and diagnostic OR. The pooled OR for the association between higher quintiles or tertiles of LAP index and CKD was 1.098 (95% CI: 1.043-1.152), with substantial heterogeneity (I²=91.2%) and evidence of publication bias. Subgroup analysis revealed a stronger association in non-diabetic (OR=2.422, 95% CI: 1.802-3.042) compared with diabetic patients (OR=1.018, 95% CI: 0.993-1.043). The diagnostic accuracy of LAP index for CKD was moderate (AUROC=0.64), with sensitivity and specificity estimates of 0.58 and 0.63, respectively. In conclusion, in the present study, LAP index demonstrated a modest but significant association with CKD, particularly in non-diabetic patients. Despite its moderate diagnostic accuracy, the LAP index could serve as a valuable tool in CKD risk stratification, particularly when integrated with other clinical markers.

Evaluating the lipid accumulation product index as a predictor for kidney stone prevalence: insights from NHANES 2007-2018.

PURPOSE: This study aimed to explore the relationship between the lipid accumulation product (LAP) index and kidney stone prevalence, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018. METHODS: An observational study was executed employing the NHANES dataset from 2007 to 2018. Analytical methods encompassed multivariate logistic regression, restricted cubic splines (RCS), subgroup analysis, and interaction tests. Predictions were made using the receiver operating characteristic (ROC) curve and the area under the curve (AUC) values. RESULTS: The analysis included 9744 adults aged 20 years and older. Multivariate logistic regression identified a significant positive association between log2-transformed LAP (treated as a continuous variable) and kidney stone risk across all models, with odds ratios (ORs) exceeding 1 and p values less than 0.001. Categorically, ORs escalated with increasing LAP levels, indicating a dose-response relationship. The RCS analysis confirmed a linear positive correlation between log2-transformed LAP and kidney stone risk. Subgroup analyses revealed that the log2-transformed LAP-kidney stones relationship was consistent, unaffected by stratification across the examined variables. In addition, LAP index (AUC = 0.600) proved to be a more effective predictor of kidney stones compared to body mass index (AUC = 0.584). CONCLUSION: Elevated LAP levels are positively correlated with a higher incidence of kidney stones, signifying its potential as a risk marker for this condition. Future research should investigate the mechanisms underlying this relationship. LAP can be used as a new anthropometric index to predict kidney stones, and its predictive ability is stronger than body mass index.

Whether weekend warriors (WWs) achieve equivalent benefits in lipid accumulation products (LAP) reduction as other leisure-time physical activity patterns? -Results from a population-based analysis of NHANES 2007-2018.

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.

Lipid-Laden Macrophages in Pulmonary Diseases.

Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.

4-tert-Butylphenol impairs the liver by inducing excess liver lipid accumulation via disrupting the lipid metabolism pathway in zebrafish.

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.

Hepatoprotective effect of dietary pterostilbene against high-fat-diet-induced lipid accumulation exacerbated by chronic jet lag via SIRT1 and SIRT3 activation.

Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high-fat-diet (HFD)-induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD-induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and ß-oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB-induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2-mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC-1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future.