Luanxun Lin, Xiaoqin Lin, Shuaidan Chang, Yiqing Xing, Tao Zhou, Chunxue Yang
{"title":"Age-specific associations between per- and polyfluoroalkyl substances exposure and metabolic syndrome: a cross-sectional study.","authors":"Luanxun Lin, Xiaoqin Lin, Shuaidan Chang, Yiqing Xing, Tao Zhou, Chunxue Yang","doi":"10.1186/s12944-025-02582-x","DOIUrl":"https://doi.org/10.1186/s12944-025-02582-x","url":null,"abstract":"<p><strong>Background: </strong>The widespread presence of per-and polyfluoroalkyl substances (PFAS) has raised global health concerns. This study aims to determine the age-specific relationships of PFAS compounds with metabolic syndrome (MetS) and its components.</p><p><strong>Methods: </strong>We used data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018. Modified Poisson regression was employed to estimate associations between individual PFAS compounds and prevalence of MetS, as well as its components. Multiple linear regression analyses were performed to examine the associations between PFAS congeners and metabolic markers, including lipid and glucose homeostasis traits. Additionally, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were conducted to investigate the joint effects of PFAS mixtures on the prevalence of MetS and its components across different age groups.</p><p><strong>Results: </strong>A total of 5850 participants were included for analysis. In the Modified Poisson regression model, ln-transformed perfluorononanoic acid (PFNA) level was positively correlated with MetS prevalence in adolescents (prevalence ratio [PR] = 1.42; 95% CI: 1.01-1.99). Conversely, ln-transformed perfluorohexanesulfonic acid (PFHxS) and ln-transformed 2-(N-Methylperfluorooctane sulfonamido) acetic acid (MeFOSAA) were negatively associated with the risks of MetS in young adults (PR = 0.86, 95% CI: 0.76-0.98) and middle-aged adults (PR = 0.88, 95% CI: 0.79-0.98), respectively. Notably, individual PFAS exposure was positively associated with levels of total cholesterol, low-density lipoprotein, non-high-density lipoprotein, and high-density lipoprotein in young and middle-aged adults. However, overall effect analyses using WQS and BKMR showed no significant associations of PFAS mixture with MetS in any age group. Nonetheless, in middle-aged adults, PFAS mixture was adversely correlated with hypertriglyceridemia and positively linked to a greater risk of hypertension and increased high-density lipoprotein cholesterol levels.</p><p><strong>Conclusions: </strong>Our study highlighted the complex relationships between PFAS exposure and the risks of MetS and its components across different age groups. Co-exposure to PFAS was particularly linked to dyslipidemia in young and middle-aged adults. Prospective studies are needed for better comprehension of the causative impact of PFAS on the risks of MetS.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"174"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Atherogenic index of plasma and triglyceride-glucose index mediate the association between stroke and all-cause mortality: insights from the lipid paradox.","authors":"Jinhua Qian, Qinjie Chi, Chengqun Qian, Xian Fan, Wenbing Ding, Tianle Wang, Li Zhu","doi":"10.1186/s12944-025-02586-7","DOIUrl":"https://doi.org/10.1186/s12944-025-02586-7","url":null,"abstract":"<p><strong>Background: </strong>The \"lipid paradox\" describes the counterintuitive observation that traditionally unfavorable lipid profiles may be associated with improved outcomes in stroke patients. Non-traditional lipid markers such as the atherogenic index of plasma (AIP) and the triglyceride-glucose (TyG) index have been proposed to better reflect the complex metabolic disturbances following stroke. This study aims to investigate the mediating role of AIP and TyG index in the association between stroke and all-cause mortality and elucidate the potential mechanisms underlying the lipid paradox.</p><p><strong>Methods: </strong>This cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS), including 10,220 participants enrolled from 2011 to 2020, with a maximum follow-up of 10 years. AIP and TyG index were calculated from baseline serum measurements. U-test, chi-square test, restricted cubic spline analysis (RCS), cox proportional hazards regression and mediation model were used to analyze the relationship between baseline AIP, TyG index, stroke and all-cause mortality.</p><p><strong>Results: </strong>A total of 1,421 deaths (13.90%) occurred during an average follow-up of 9.21 years. Compared to survivors, non-survivors were older, had a higher prevalence of stroke, and lower AIP levels (P < 0.05), while TyG index showed no significant group difference. RCS analysis revealed a nonlinear association between the TyG index and mortality, but no significant nonlinearity for AIP. Cox regression analysis identified age, gender, marital status, smoking history, hypertension, diabetes, lung disease, stroke, AIP, and the highest TyG quartile (Q4) as independent predictors of all-cause mortality (all P < 0.05). Notably, AIP showed a negative association with mortality (HR = 0.87, 95% CI: 0.77-0.98),demonstrating a lipid paradox phenomenon. Furthermore, in the chain mediation model, both AIP (β=-0.03, 95%CI: -0.072 to -0.002) and TyG index (β=-0.016, 95%CI: -0.036 to -0.002) independently mediated the association between stroke and all-cause mortality in a negative manner. However, the positive chain mediating effect of AIP through TyG index (β = 0.028, 95%CI: 0.003-0.066) offset this negative mediation, rendering the overall mediating effect insignificant.</p><p><strong>Conclusions: </strong>AIP and the TyG index independently or jointly influence the risk of all-cause mortality after stroke. Notably, AIP demonstrates a significant lipid paradox phenomenon. Moreover, the chain mediating effect of AIP and TyG significantly increases post-stroke mortality risk. These findings highlight the complex interplay between lipid and glucose metabolism in stroke prognosis and offer a novel perspective for post-stroke metabolic management.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"173"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between saturated and polyunsaturated fatty acid proportions in total fat intake and mortality risk: mediation by the neutrophil percentage-to-albumin ratio.","authors":"Yanyan Liu, Jiaxuan Wang, Xiaona Chang, Xiaoying Ren, Guang Wang, Jia Liu","doi":"10.1186/s12944-025-02592-9","DOIUrl":"https://doi.org/10.1186/s12944-025-02592-9","url":null,"abstract":"<p><strong>Background: </strong>For over half a century, dietary guidelines have consistently advocated for the substitution of saturated fatty acids (SFA) with monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) as a cornerstone strategy for health life, but evidence on independent associations between specific fatty acids and mortality remains inconsistent.</p><p><strong>Methods: </strong>This prospective cohort study from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 analyzed 21,823 participants aged 20-80 years. Survey-weighted Cox regression assessed associations between SFA, MUFA, PUFA intake, and their ratios to the total fat (TFAT) intake quantity, and all-cause mortality. Mediation analyses examined whether the neutrophil percentage-to-albumin ratio (NPAR) mediated the effects of fatty acid-related parameters on mortality risk.</p><p><strong>Results: </strong>In multivariable-adjusted models, no significant trends were observed for all-cause mortality across tertiles of SFA, MUFA, or PUFA intake. In multivariable-adjusted Cox models, the highest tertile of SFA/TFAT ratio was significantly associated with elevated mortality risk (HR = 1.23, p for trend < 0.01). Conversely, the highest PUFA/TFAT tertile demonstrated a protective association (HR = 0.86, p for trend < 0.01). However, the MUFA/TFAT ratio showed no significant mortality association across tertiles (p for trend = 0.137). Mediation analysis revealed that NPAR mediated 9.8% and 11.8% of SFA/TFAT and PUFA/TFAT effects on mortality risk, suggesting partial mediation through a shared inflammatory pathway.</p><p><strong>Conclusion: </strong>This study provides the novel evidence that the proportional composition of dietary fatty acids within total fat intake-rather than their absolute intake levels-is a critical determinant of longevity. By demonstrating that replacing SFA with PUFA reduces mortality risk through NPAR-mediated inflammatory pathways, our findings inform the World Health Organization's 2023 guidelines on dietary fat modification. These results shift the paradigm from isolated nutrient restrictions to balanced fatty acid ratios, offering a novel mechanistic basis for public health strategies aimed at extending healthy lifespan.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"175"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammatory markers mediate the association between alternative adiposity indices and mortality in patients with rheumatoid arthritis: data from NHANES 1999-2018.","authors":"Feng Luo, Jia-Jie Guo, Xue-Mei Yuan, Heng Zhou, Qiu-Yi Wang, Chang-Ming Chen, Xue-Ming Yao, Wu-Kai Ma","doi":"10.1186/s12944-025-02584-9","DOIUrl":"https://doi.org/10.1186/s12944-025-02584-9","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with increasing mortality worldwide. Traditional obesity indicators inadequately predict the mortality risk in this population. Thus, the research aimed to evaluate new obesity indicators to explore their close association with RA mortality.</p><p><strong>Methods: </strong>This study analyzed 101,316 National Health and Nutrition Examination Survey participants (1999-2018) to evaluate alternative adiposity indices for RA mortality prediction. Missing data were imputed using the random forest method. Key covariates were selected using the Boruta algorithm and weighted univariate Cox regression. Multivariable-adjusted models generated hazard ratios (95% confidence interval), validated by time-dependent receiver operating characteristic curves and Harrell's C-index. Survival patterns were assessed with restricted cubic splines (RCS) and Kaplan-Meier curves. Threshold effects and robustness were analyzed via segmented Cox models and sensitivity analyses. Extreme gradient boosting (XGBoost) identified A Body Shape Index (ABSI) as the strongest predictor.</p><p><strong>Results: </strong>Among the 1,266 individuals, 299 deaths occurred during follow-up (190 all-cause, 59 cardiovascular, 50 cancer). ABSI predicted the 5-, 10-, and 20-year mortality (area under the curve: 0.823, 0.801, 0.752, respectively) and outperformed other indices in the Harrell's C-index. Weighted multivariable Cox regression linked higher ABSI × 100 values with increased mortality; Kaplan-Meier curves confirmed reduced survival in the highest quartile (P < 0.001). RCS revealed a U-curve association linking ABSI × 100 to mortality. Moreover, the mediating effects analysis indicated the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio, Neutrophil-to-Lymphocyte Ratio, Advanced Lung Cancer Inflammation Index, and Systemic Immune-Inflammation Index played significant roles as mediators, with mediation ratios of 4.9%, 5.1%, 8.5%, and 4.5%, respectively. Additional sensitivity analyses validated these results. Quartile stratification revealed a pronounced risk amplification in the highest quartile (Q4), particularly in the fully adjusted specification (Hazard ratio = 3.43, 1.45-8.14; P = 0.005). Furthermore, XGBoost results indicate that ABSI is the best obesity metric for predicting the prognosis of patients with RA.</p><p><strong>Conclusions: </strong>This study revealed a potential clinical value of a new obesity index, specifically the ABSI, in predicting the survival rates among individuals with RA. Inflammatory markers appear to play a partial mediating role in this relationship.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"170"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between eosinophil number and overweight status: a nonlinear, bidirectional study.","authors":"Xinghai Yue, Chenchen Wang, Xixu Zhang","doi":"10.1186/s12944-025-02581-y","DOIUrl":"https://doi.org/10.1186/s12944-025-02581-y","url":null,"abstract":"<p><strong>Background: </strong>The relationship between eosinophil number and overweight status (or obesity) remains a subject of debate. While animal studies suggest a negative correlation between the two, most clinical studies indicate a positive correlation. Therefore, we hypothesize that a nonlinear relationship may exist between eosinophil number and overweight status. This study aims to investigate the association between eosinophil number and overweight status (as well as related indicators) using data from the National Health and Nutrition Examination Survey (NHANES).</p><p><strong>Methods: </strong>We utilized data from NHANES 1999-2018, where eosinophil number was obtained from laboratory tests. Overweight status was defined as a body mass index (BMI) ≥ 25. We then applied weighted logistic regression/linear regression, subgroup analysis, and restricted cubic splines (RCS) analysis to investigate the association between eosinophil number and overweight status (as well as related indicators).</p><p><strong>Results: </strong>A total of 77,217 individuals were included in this study, with 38,106 individuals in the non-overweight group (BMI < 25) and 39,111 individuals in the overweight group (overweight and obesity, BMI ≥ 25). The logistic regression analysis revealed a significant association between eosinophil number and overweight status (OR: 2.38, 95% CI: 1.81-3.12, P < 0.001). Additionally, eosinophil number was significantly positively correlated with obesity/BMI/triglycerides and negatively correlated with High-Density Lipoprotein (HDL). Finally, the nonlinear regression results indicated an inverted U-shaped relationship between eosinophil number and overweight status/obesity/BMI.</p><p><strong>Conclusion: </strong>Our study demonstrates an inverted U-shaped relationship between eosinophil number and overweight status/obesity/BMI. Eosinophil number is also significantly associated with HDL and triglycerides. These findings suggest that eosinophils may play a role in overweight (or obesity) and provide valuable insights for exploring the underlying immune mechanisms of overweight status.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"172"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Le Xu, Jian Xu, Wanting Shi, Sa Zhang, Ting Guo, Shien Zou
{"title":"Decreased protein activator of interferon induced protein kinase (PRKRA) involved in menopause-related cholesterol metabolic disorders by regulating cholesterol biosynthesis.","authors":"Le Xu, Jian Xu, Wanting Shi, Sa Zhang, Ting Guo, Shien Zou","doi":"10.1186/s12944-025-02575-w","DOIUrl":"https://doi.org/10.1186/s12944-025-02575-w","url":null,"abstract":"<p><strong>Background: </strong>Menopause-related cholesterol metabolic disorders pose a global health concern, but the underlying mechanism is unclear. PRKRA was identified as a potential regulator of cholesterol metabolism in an exome-wide association study. Our prior research revealed a decrease in PRKRA expression in the ovarian cortex of postmenopausal women. However, its involvement in cholesterol metabolism disturbances in postmenopausal females remains unclear. This study aimed to investigate the association between PRKRA and cholesterol metabolism disorders in ovariectomized mice. Additionally, we elucidated the impact and underlying mechanisms of PRKRA on cholesterol metabolism in HepG2 and HuH7 cells.</p><p><strong>Methods: </strong>An ovariectomized mouse model was generated, and the mice were fed a standard diet for six months to simulate menopausal conditions. PRKRA expression in mouse liver tissue was evaluated by qPCR and western blotting. Spearman correlation analysis was used to explore the relationship between the PRKRA mRNA level and the serum total cholesterol concentration. In vitro, we investigated the influence of PRKRA on cholesterol levels and Dil-LDL uptake capacity in HepG2 and HuH7 cells. Additionally, transcriptome sequencing was employed to analyze the intrinsic mechanisms involved.</p><p><strong>Results: </strong>The ovariectomized mouse model exhibited abnormal lipid profiles that correlated with reduced PRKRA expression in the liver. In vitro, 17β-estradiol (E<sub>2</sub>) upregulated PRKRA expression, while follicle-stimulating hormone (FSH) downregulated it in HepG2 and HuH7 cells. PRKRA knockdown increased intracellular total cholesterol and decreased Dil-LDL uptake, while PRKRA overexpression had the opposite effects. Mechanistically, reduced PRKRA levels were associated with HMGCS1 upregulation and LDLR downregulation.</p><p><strong>Conclusion: </strong>Ovariectomy for six months independently induced an aberrant cholesterol phenotype in mice. Downregulation of PRKRA was implicated in cholesterol metabolism disturbances related to menopause, potentially through the regulation of cholesterol synthesis and LDL uptake.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"171"},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiple machine learning algorithms identify 13 types of cell death-critical genes in large and multiple non-alcoholic steatohepatitis cohorts.","authors":"Renao Jiang, Longfei Dai, Xinjian Xu, Zhen Zhang","doi":"10.1186/s12944-025-02588-5","DOIUrl":"https://doi.org/10.1186/s12944-025-02588-5","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated programmed cell death pathways mechanistically contribute to hepatic inflammation and fibrogenesis in non-alcoholic steatohepatitis (NASH). Identification of cell death genes may offer insights into diagnostic and therapeutic strategies for NASH.</p><p><strong>Methods: </strong>Data from multiple NASH cohorts were integrated, and 12 machine learning algorithms were applied to identify key dysregulated cell death-related genes and develop a binary classification model for NASH. Spearman's rank correlation coefficients quantified associations between these genes and clinical markers, immune infiltration profiles, and signature genes encoding pro-inflammatory mediators, metabolic regulators, and fibrotic drivers. Gene set enrichment analysis (GSEA) was performed to delineate the mechanistic underpinnings of these key genes. Consensus clustering analysis was then used to stratify patients with NASH into distinct phenotypic subgroups based on expression levels of these genes.</p><p><strong>Results: </strong>A NASH prediction model, developed using the random forest (RF) algorithm, demonstrated high diagnostic accuracy across multiple cohorts. Four key genes, enriched in lipid metabolism and inflammation pathways, were identified. Their transcriptional levels were significantly correlated with the non-alcoholic fatty liver disease activity score (NAS), hepatic inflammatory infiltration, molecular signatures of metabolic dysregulation (lipid homeostasis regulators), and fibrosis progression. These genes also enabled accurate classification of patients with NASH into clusters reflecting varying disease severity.</p><p><strong>Conclusions: </strong>A binary classification model, developed using the RF algorithm, accurately identified patients with NASH. The four cell death genes, identified through 12 machine learning algorithms, represent potential biomarkers and therapeutic targets for NASH. These genes contribute to inflammation-related immune cell activation, lipid metabolism dysregulation, and liver fibrosis, highlighting the complex interplay between cell death and NASH progression.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"169"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yifan Hao, Xuerui Li, Yiting Zhang, Jun Zheng, Yuyang Miao, Jin Tan, Qiang Zhang
{"title":"Combined effect of fasting blood glucose and serum uric acid on nonalcoholic fatty liver disease.","authors":"Yifan Hao, Xuerui Li, Yiting Zhang, Jun Zheng, Yuyang Miao, Jin Tan, Qiang Zhang","doi":"10.1186/s12944-025-02538-1","DOIUrl":"https://doi.org/10.1186/s12944-025-02538-1","url":null,"abstract":"<p><strong>Background: </strong>This study sought to investigate the independent and synergistic impacts of fasting blood glucose (FBG) and serum uric acid (SUA) levels on non-alcoholic fatty liver disease (NAFLD) in participants with and without type 2 diabetes mellitus (T2DM).</p><p><strong>Method: </strong>A total of 12,430 participants (mean age: 54.34 ± 15.23, 34.34% female) were enrolled through the Health Screening Center of Tianjin Medical University General Hospital. FBG was classified as < 6 mmol/L, 6-7 mmol/L, and ≥ 7 mmol/L. SUA was classified into two categories: normal SUA and hyperuricemia (SUA level ≥ 420 µmol/L for men, ≥ 360 µmol/L for women). T2DM was ascertained through self-reported data. The diagnosis of NAFLD is established via abdominal ultrasound imaging. Logistic regression models and interaction effect models are used for data analysis.</p><p><strong>Result: </strong>Of the 12,430 participants, 4846 (38.99%) were diagnosed with NAFLD. In comparison to individuals with FBG < 6 mmol/L and no self-reported T2DM, those with FBG ≥ 7 mmol/L and no self-reported T2DM exhibited the highest prevalence of NAFLD (odds ratio [OR] 2.91, 95% CI 2.16-3.93) following multi-adjusted analysis. In the joint effect analysis of FBG and SUA, FBG ≥ 7 mmol/L and hyperuricemia were linked to a greater prevalence of NAFLD compared to FBG < 6 mmol/L and normal SUA, both in individuals with self-reported T2DM (OR 2.92, 95% CI 1.68-5.05) and those without self-reported T2DM (OR 7.87, 95% CI 3.57-17.34). An additive interaction existed between FBG and SUA regarding NAFLD in individuals without self-reported T2DM (AP 0.488, 95% CI: 0.068-0.909, P = 0.02).</p><p><strong>Conclusion: </strong>Elevated FBG levels are associated with NAFLD irrespective of self-reported T2DM status. The concomitant elevation of FBG and SUA levels exhibits a significant correlation with NAFLD, particularly in individuals lacking self-reported T2DM.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"168"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dandan Hu, Litian Wang, Lin Qi, Xiangxuan Yang, Yamin Jin, Huailiu Yin, Yewei Huang, Jun Sheng, Xuanjun Wang
{"title":"Resveratrol improved atherosclerosis by increasing LDLR levels via the EGFR-ERK1/2 signaling pathway.","authors":"Dandan Hu, Litian Wang, Lin Qi, Xiangxuan Yang, Yamin Jin, Huailiu Yin, Yewei Huang, Jun Sheng, Xuanjun Wang","doi":"10.1186/s12944-025-02585-8","DOIUrl":"https://doi.org/10.1186/s12944-025-02585-8","url":null,"abstract":"<p><strong>Background and aims: </strong>Atherosclerosis (AS) is a complex and chronic vascular disease and elevated low-density lipoprotein cholesterol (LDL-C) level is one of its primary causative factors. As a key surface receptor, low-density lipoprotein receptor (LDLR) plays an essential role in LDL-C clearance. Resveratrol (RSV) has emerged as a promising compound for investigating potential therapeutic targets for AS due to its ability to lower cholesterol, reduce endothelial anti-inflammatory and suppress vascular smooth muscle cell proliferation. This study explored the effects of RSV on AS through upregulating LDLR and analyzed the mechanism through a combination of in vivo and vitro experiments.</p><p><strong>Methods: </strong>HepG2 cells were exposed to varying concentrations of RSV. The effects of RSV on LDLR expression and cholesterol uptake were analyzed by western blot, RT-qPCR and DiI-LDL uptake assay. In vivo, C57BL/6J ApoE<sup>-/-</sup> mice were used and the experimental groups were treated with RSV, Lovastatin and Gefitinib. Plaque formation in the arteries and aortic roots was assessed by Oil Red O staining and plaque stability was evaluated using Hematoxylin-Eosin (H&E) and Elastic Van Gieson (EVG) staining. Western blot, RT-qPCR and immunohistochemical staining were employed to analyze the expression of LDLR in the livers of mice.</p><p><strong>Results: </strong>RSV significantly enhanced the stability of LDLR mRNA and promoted LDLR protein expression. The inhibition experiments of EGFR signaling pathway (Cetuximab and Gefitinib) demonstrated that the efficacy of RSV was markedly weakened when this signaling pathway was inhibited. It indicated that RSV modulated LDLR gene expression by activating EGFR-ERK1/2 pathway. In ApoE<sup>-/-</sup> mice, RSV notably reduced arterial plaque formation, improved plaque stability and increased hepatic LDLR expression.</p><p><strong>Conclusion: </strong>This study elucidated the mechanism by which RSV upregulates LDLR gene expression through activating EGFR-ERK1/2 signaling pathway. In vivo experiments demonstrated its efficacy in reducing arterial plaque formation and stabilizing existing plaques. These results further indicated that RSV held potential therapeutic value for ameliorating atherosclerosis and cardiovascular diseases. Collectively, these findings provided novel theoretical support for RSV's potential role in cardiovascular therapy.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"167"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between relative fat mass and cognitive function among US older men: NHANES 2011-2014.","authors":"Linlin Liu, Anshi Wu, Shengnan Yang","doi":"10.1186/s12944-025-02593-8","DOIUrl":"https://doi.org/10.1186/s12944-025-02593-8","url":null,"abstract":"<p><strong>Background: </strong>Relative fat mass (RFM) is a new metric developed to assess the entire body fat proportion in adults. The objective of this study was to examine the correlation between cognitive performance and RFM in older American males.</p><p><strong>Methods: </strong>A total of 1,321 individuals were selected from the National Health and Nutrition Examination Survey (NHANES) that was carried out between the years 2011 and 2014. Specifically, the Consortium to Establish a Registry for Alzheimer's Disease Word Learning Test (CERAD-WL), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) were used in order to achieve the objective of assessing cognitive function. The standardized scores of the three previously mentioned tests were averaged to create the Z-scores, a composite, generalized metric. RFM was ascertained by measuring waist circumference (WC) and height. The relationships that exist between RFM and cognitive performance were investigated using a variety of statistical methods, including multivariate linear regression, threshold effect analyses, smooth curve fitting, and subgroup analyses.</p><p><strong>Results: </strong>The study included 1,321 male volunteers aged 60 years or older, and comprehensive data was provided for each individual. Fully adjusted models indicated a negative correlation between RFM and CERAD-WL scores[-0.17, (-0.32,-0.01)], DSST scores[-0.83, (-1.16,-0.50)] and Z-scores[-0.03, (-0.05, -0.01)]. It was observed that the negative correlation that exists between RFM and Z-scores became more pronounced when RFM exceeded 35.78. Furthermore, subgroup analyses showed that the association between RFM and cognitive function was significantly impacted by education level, poverty-income ratio (PIR), smoking status, and drinking status.</p><p><strong>Conclusions: </strong>A higher RFM was linked to lower cognitive function in older men, suggesting that management of RFM may prove advantageous in mitigating cognitive decline among older male populations.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"166"},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}