Lipids in Health and Disease最新文献

{"title":"Systemic inflammation response index mediates the association between relative fat mass and psoriasis risk: a population-based study.","authors":"Xinyi Shao, Jun Yu, Qian Liu, Yidian Fu, Aijun Chen, Genlong Bai, Jingbo Zhang","doi":"10.1186/s12944-025-02528-3","DOIUrl":"10.1186/s12944-025-02528-3","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis, a prevalent autoimmune skin condition, considerably impairs the quality of life of those who are affected by it. Several studies have demonstrated that obesity significantly contributes to both the onset and progression of psoriasis. Relative fat mass (RFM), a novel obesity index, provides a more precise measure by incorporating both height and waist circumference (WC). The aim of this study was to investigate the association between RFM and psoriasis risk, taking into account the intermediary role played by the systemic inflammation response index (SIRI).</p><p><strong>Methods: </strong>The cross-sectional study assessed data from 8,479 adults who participated in the NHANES cycles from 2003 to 2006 and 2009 to 2014. To examine the association between RFM and psoriasis, both multivariate logistic regression model and restricted cubic spline (RCS) analyses were conducted. A mediation analysis was used to clarify the role of SIRI in the association between RFM and psoriasis.</p><p><strong>Results: </strong>Higher RFM was significantly associated with a 5% higher risk of developing psoriasis (odds ratio [OR] = 1.05, 95% confidence interval [CI]:1.02-1.08), with RFM quartiles indicating a significant trend (P _{for trend} < 0.05). The SIRI demonstrated a significant mediating effect on the RFM-psoriasis relationship (mediation effect ratio = 5.02%).</p><p><strong>Conclusion: </strong>Elevated RFM are associated with an increased prevalence of psoriasis. RFM has the potential to be a beneficial anthropometric measure for more accurately predicting psoriasis risk.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"119"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730417","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":"Arachidonic acid suppresses lung cancer cell growth and modulates lipid metabolism and the ERK/PPARγ signaling pathway.","authors":"Lin Wang, Lanlan Wei, Xueling Chen, Jiali Xiong","doi":"10.1186/s12944-025-02490-0","DOIUrl":"10.1186/s12944-025-02490-0","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related mortality worldwide, necessitating the development of new treatment strategies. Arachidonic acid (ARA), a polyunsaturated fatty acid, shows promise in cancer therapy due to its potential anti-tumor effects, although its role in lung cancer remains unclear. This study investigated the effects and underlying mechanism of ARA on A549 and NCI-H1299 lung cancer cells. In vitro assays were used to assess cell viability, apoptosis, colony formation, lipid droplet formation, and changes in cellular lipid content. ARA dose-dependently suppressed cell viability, facilitated apoptosis, and suppressed colony formation in both lung cancer cell lines. Network pharmacology analysis was performed to identify potential gene targets and pathways, uncovering 61 overlapping genes between ARA and lung cancer-related targets, with mitogen-activated protein kinase 1 (MAPK1) emerging as a key gene. Enrichment analyses suggested that the effects of ARA might be mediated through lipid metabolism and the extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. In both lung cancer cell lines, ARA treatment inhibited lipid droplet formation and decreased the cellular lipids. Immunoblotting further confirmed that ARA treatment significantly increased ERK phosphorylation while reducing PPARγ and fatty acid synthase (FASN) protein levels. In vitro experiments using GW9662, a PPARγ antagonist, confirmed that inhibiting lipid droplet formation impairs lung cancer cell viability and promotes apoptosis. Furthermore, in vivo experiments demonstrated that ARA significantly reduced tumor size and weight in a lung cancer xenograft model, further validating its anti-tumor effects. The potential of ARA as a therapeutic agent for lung cancer might involve lipid metabolism and relevant signaling pathways. A future study exploring the full therapeutic potential of ARA and underlying mechanisms in lung cancer is needed.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"114"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719772","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":"Lipid profiles, lipid ratios and 28-day mortality risk in non-surgical older patients with critical illnesses: a retrospective cohort study using hospitalization records.","authors":"Yang Li, Jianli Ge, Shasha Geng, Qingqing Li, Xin Chen, Yingqian Zhu, Xiaotong Guo, Huajie Gu, Yue Liu","doi":"10.1186/s12944-025-02545-2","DOIUrl":"10.1186/s12944-025-02545-2","url":null,"abstract":"<p><strong>Background and aims: </strong>The relationship between dyslipidemia and mortality varies by age, with an inverse association observed in the oldest age groups. There is limited research examining lipid profiles' correlation with short-term mortality risk in older adults. This study aimed to investigate associations of lipid profiles and lipid ratios with 28-day mortality risk in non-surgical older patients with critical illnesses.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted with non-surgical older patients with critical illness who were admitted to the ICU of Shanghai East Hospital between January 2022 and November 2024. All data were collected via the hospitalization information system. Elastic network models were used to select covariates and Cox proportional hazards models were constructed to examine the association of lipid profiles and lipid ratios with 28-day mortality risk. Restricted cubic splines were used to test for non-linear relationships. Subgroup analyses were performed based on median age and gender.</p><p><strong>Results: </strong>The median age of study's participants was 75 years, 35.91% of whom were female. Those who died within 28 days were more likely to receive dopamine, norepinephrine and mechanical ventilation than survivors. Adjusted models indicated that LDLC (HR = 0.82, 95% CI: 0.69 to 0.97), lbLDLC (HR = 0.79, 95% CI: 0.63 to 0.98), sdLDLC (HR = 0.44, 95% CI: 0.24 to 0.83), LDLC/HDLC (HR = 0.85, 95% CI: 0.73 to 1.00), and sdLDLC/HDLC (HR = 0.63, 95% CI: 0.40 to 1.00) were associated with decreased 28-day mortality risk. However, no non-linear associations were detected. In younger older adults (age < 75 years), TC, non HDLC, remanent C, TC/HDLC and remanent C/HDLC were related to increased short-term mortality risk. In very old adults, TC, LDLC, lbLDLC, sdLDLC, non HDLC, TC/ HDLC, LDLC/HDLC, lbLDLC/HDLC, and sdLDLC/HDLC were associated with lower 28-day mortality risk. In women, only lower sdLDLC was associated with increased short-term mortality risk.</p><p><strong>Conclusion: </strong>Lower levels of LDLC and its subtypes (lbLDLC, sdLDLC) were associated with increased 28-day mortality risk, particularly in patients aged ≥ 75 years and women. Conversely, elevated residual cholesterol levels correlated with higher mortality in younger older adults (< 75 years). These findings underscore the need for age- and sex-specific lipid management strategies in older patients with critical illnesses.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"122"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730466","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":"Effectiveness of body roundness index for the prediction of nonalcoholic fatty liver disease: a systematic review and meta-analysis.","authors":"Shaghayegh Khanmohammadi, Parisa Fallahtafti, Amirhossein Habibzadeh, Ali Ezzatollahi Tanha, Amir Ali Alamdari, Parsa Fallahtafti, Mohammad Shafi Kuchay","doi":"10.1186/s12944-025-02544-3","DOIUrl":"10.1186/s12944-025-02544-3","url":null,"abstract":"<p><strong>Background: </strong>Several anthropometric indices, such as body mass index and waist circumference, have been used as clinical screening tools for the prediction of nonalcoholic fatty liver disease (NAFLD). To further refine these clinical tools for NAFLD, the body roundness index (BRI) has recently been evaluated. In this systematic review and meta-analysis, the objective was to evaluate the relationship and predictive capability of the BRI in identifying NAFLD.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Embase, Web of Science, and Scopus up to December 31, 2024. Eligibility criteria included observational studies on adults (≥ 18 years old) with measured BRI and its association with NAFLD. The Joanna Briggs Institute tool was used for risk of bias assessment. Meta-analyses used random-effects models to pool data on mean difference, odds ratio, sensitivity, specificity, and the area under the curve (AUC), with heterogeneity and publication bias assessed.</p><p><strong>Results: </strong>Ten studies involving 59,466 participants were included. The pooled mean difference in BRI between the NAFLD and non-NAFLD groups was 1.73 (95% confidence interval [CI]: 1.31-2.15). The pooled sensitivity and specificity of BRI for diagnosing NAFLD were 0.806 and 0.692, respectively. The pooled AUC for BRI was 0.803 (95% CI: 0.775-0.830), indicating good diagnostic accuracy. Unlike subgroup analysis by country, subgroup analysis by sex showed no significant differences. Higher BRI values were associated with increased odds of NAFLD (pooled OR = 2.87, 95% CI: 1.39; 5.96). Studies provided mixed results on the predictive ability of BRI compared to other indices like body mass index, mostly favoring BRI over conventional indices.</p><p><strong>Conclusion: </strong>BRI demonstrates a good diagnostic performance for NAFLD, suggesting it may be a valuable clinical tool for NAFLD assessment. Further research is necessary to validate these findings and strengthen the evidence base.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"117"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730336","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":"Changes in polyunsaturated fatty acids are linked to metabolic syndrome in children with steroid-sensitive nephrotic syndrome-a clinical observation.","authors":"Pei-Long Li, Hong-Min Fu, Kai Liu, Jia-Wu Yang, Yuan Liao, Feng Li","doi":"10.1186/s12944-025-02535-4","DOIUrl":"10.1186/s12944-025-02535-4","url":null,"abstract":"<p><strong>Objective: </strong>Alterations in lipid metabolic pathways constitute a pivotal characteristic of Steroid-Sensitive Nephrotic Syndrome (SSNS). Despite the significance, there has been scant exploration into the influence of polyunsaturated fatty acids (PUFAs) on metabolic syndrome (MetS) in children with SSNS. This study endeavors to elucidate the association between PUFAs and MetS in this specific pediatric population.</p><p><strong>Methods: </strong>This study enrolled a total of 185 children aged 0-7 years with SSNS between May 2023 and May 2024. Based on international guidelines for MetS, patients were classified into a MetS group (n = 73) and a non-MetS group (n = 112). A healthy control group (n = 82) was also established. Surveys, anthropometric measurements, and blood samples were used to assess lipid profiles, glucose, insulin, and Hemoglobin A1C (HbA1C). The concentrations of serum PUFAs were quantitatively analyzed utilizing gas chromatography-mass spectrometry (GC-MS) techniques.</p><p><strong>Results: </strong>The MetS group exhibited significantly elevated levels of fasting blood glucose, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, HbA1C, insulin, the ratio of TG to high-density lipoprotein (HDL) cholesterol, and the ratio of total cholesterol to HDL cholesterol compared to the non-MetS group. Significant differences were observed among healthy controls, MetS group, and non-MetS group in terms of ω-3 alpha-linolenic acid (ALA), ω-3 docosahexaenoic acid (DHA), ω-6 arachidonic acid, and ω-6 to ω-3 ratio.</p><p><strong>Conclusions: </strong>High ω-6 arachidonic acid, ω-6/ω-3 ratio and low ω-3 ALA and ω-3 DHA were associated with elevated TG levels. An elevation in TG concentrations among pediatric patients with SSNS may have been implicated to MetS.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"115"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719776","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 exposure to brominated flame retardants (BFRs) and blood lipid profiles in American adults: a cross-sectional study.","authors":"Yuxuan Wang, Zhihao Zhang, Nana Shen, Xiaoying Qi, Hao Li, Futong Wu, Zhongze Zhu, Jiarui Liu, Hongfei Xiang","doi":"10.1186/s12944-025-02527-4","DOIUrl":"10.1186/s12944-025-02527-4","url":null,"abstract":"<p><strong>Background: </strong>Exposure to brominated flame retardants (BFRs) has been linked to alterations in human metabolism and disease processes. However, the relationship between BFR exposure and blood lipid levels remains unclear. This study aimed to investigate the potential association between BFR exposure and blood lipid profiles in American adults.</p><p><strong>Methods: </strong>A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Serum concentrations of twelve BFRs, PBB153 and eleven polybrominated diphenyl ethers (PBDEs), were quantified using isotope dilution gas chromatography/high-resolution mass spectrometry (GC/HRMS). Blood lipid levels, including total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were measured enzymatically. The Friedewald equation was used to determine low-density lipoprotein cholesterol (LDL-C): [LDL-C] = [TC] - [HDL-C] - [TG/5]. Remnant cholesterol (RC) was calculated using the formula: [RC] = [TC] - [HDL-C] - [LDL-C]. Multivariable regression analyses were applied to examine the associations between individual BFRs and TC, HDL-C, LDL-C, and RC. The overall associations of BFR mixtures with blood lipids were evaluated using quantile g-computation (QGC) analyses and weighted quantile sum (WQS) regression. In order to identify potential gender-specific differences, stratified mixture analyses were performed by gender.</p><p><strong>Results: </strong>A total of 3,154 eligible participants were included. Nine BFRs with a detection rate greater than 70% were included in the analysis. Individually, PBB153, PBDE209, PBDE153, and PBDE28 were positively associated with TC and RC after adjusted all covariates. Furthermore, PBB153, PBDE209, and PBDE153 were positively associated with LDL-C. No association was found between individual BFR and HDL-C. WQS and QGC analyses confirmed that BFR mixtures were positively associated with TC, LDL-C, and RC.</p><p><strong>Conclusion: </strong>This study demonstrates that BFR exposure is associated with increased levels of TC, LDL-C, and RC, indicating an elevated risk of dyslipidemia and cardiovascular diseases.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"120"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730316","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":"Different action of glucocorticoid receptor in adipose tissue remodelling to modulate energy homeostasis by chronic restraint stress.","authors":"Yinghua Luo, Qinyu Liu, Yaqian Mao, Junping Wen, Gang Chen","doi":"10.1186/s12944-025-02539-0","DOIUrl":"10.1186/s12944-025-02539-0","url":null,"abstract":"<p><strong>Background: </strong>Chronic stress in daily life is a well-known trigger for various health issues. Despite advancements in obesity research, the mechanisms governing lipid metabolism in adipose tissue during cachexia remain poorly understood.</p><p><strong>Methods: </strong>A chronic restraint stress (CRS) model was used to induce significant physiological and psychological stress in mice. Mice were subjected to 6 h of restraint daily in 50 mL plastic tubes for seven consecutive days. A fasting control group was included for comparison. Post-stress assessments included behavioural tests, glucose and insulin tolerance tests and indirect calorimetry. Blood and adipose tissue samples were collected for mRNA and protein analyses.</p><p><strong>Results: </strong>CRS induced significant psychological and physiological changes in mice, including depression-like behaviours, weight loss and reduced insulin sensitivity. Notably, CRS caused extensive adipose tissue remodelling. White adipose tissue (WAT) underwent significant 'browning' accompanied by an increase in the expression of thermogenic proteins. This counteracted the stress-induced 'whitening' of brown adipose tissue (BAT), which exhibited impaired thermogenesis and functionality, thereby maintaining energy balance systematically. The glucocorticoid receptor (GR) plays a crucial role in lipid metabolism regulation during these changes. GR expression levels were inversely correlated in BAT and WAT, but aligned with the expression patterns of thermogenic proteins across adipose tissues. These findings suggest that under chronic metabolic stress, GR mediates tissue-specific responses in adipose tissues, driving functional and phenotypic transitions in BAT and WAT to maintain energy homeostasis.</p><p><strong>Conclusions: </strong>This study provides novel insights into the contrasting thermogenic phenotypes of BAT and WAT under emaciation and highlights the critical role of GRs in adipose tissue remodelling during CRS and its potential as a therapeutic target. Addressing GR-mediated changes in adipose tissues may help alleviate BAT dysfunction in cachexia and promote WAT browning, enhancing metabolic stress resistance.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"121"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730334","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":"Familial hypercholesterolemia in patients with hypertension: the China H-type Hypertension Registry Study.","authors":"Tianzhou Shen, Renfei Luo, Hongdong Jiang, Huihui Bao, Long Jiang, Xiaoshu Cheng","doi":"10.1186/s12944-025-02514-9","DOIUrl":"10.1186/s12944-025-02514-9","url":null,"abstract":"<p><strong>Background and aims: </strong>Familial hypercholesterolemia (FH) significantly amplifies the risk of developing atherosclerotic cardiovascular disease (ASCVD). This study investigated the prevalence and clinical characteristics of FH in a hypertensive rural population.</p><p><strong>Methods: </strong>In the China H-type Hypertension Registry Study, a prospective observational cohort study with a 4-year follow-up, 14,234 hypertensive participants from rural areas were enrolled in 2018, with onsite exams conducted in 2022. FH was identified using the Chinese-modified Dutch Lipid Clinic Network criteria.</p><p><strong>Results: </strong>Among the 10,900 patients with hypertension, 5,675 (52.1%) were women, the median age was 65 years, the median blood pressure was 146/89 mmHg, 629 (5.8%) had previous coronary heart disease (CHD), and 4,726 (43.4%) were smokers. Among the cohort, 78 (0.72%) met the C-DLCN criteria for probable or definite FH. The rate of lipid-lowering therapy (LLT) usage in patients with FH reached 35.9%. After a median follow-up period of 1,477 days, a total of 658 deaths, 535 strokes, and 309 cardiovascular disease (CVD) events were observed. At baseline and subsequent follow-up, all patients with FH were at high or ultra/very high risk for ASCVD. During follow-up, a greater decrease in LDL-C was shown in patients with FH (FH: - 31%, 95% CI - 44.6% to -14.6%; P < 0.001) than patients without FH (2%, 95% CI: - 12.1% to 17.4%); however, only 3.6% of them achieved the recommended LDL-C targets based on ASCVD risk assessment. The risks of stroke and CVD were not significantly different between patients with and without FH after 4 years of follow-up.</p><p><strong>Conclusions: </strong>This study highlights a marked gap between the high prevalence and low treatment rates of FH in rural populations with hypertension. These findings suggest the need to improve knowledge regarding FH and the need to treat this condition, especially when associated risk factors are present.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"116"},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719782","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":"Druggable genome-wide Mendelian randomization identifies therapeutic targets for metabolic dysfunction-associated steatotic liver disease.","authors":"Xiaohui Ma, Li Ding, Shuo Li, Yu Fan, Xin Wang, Yitong Han, Hengjie Yuan, Longhao Sun, Qing He, Ming Liu","doi":"10.1186/s12944-025-02515-8","DOIUrl":"10.1186/s12944-025-02515-8","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects > 25% of the global population, potentially leading to severe hepatic and extrahepatic complications, including metabolic dysfunction-associated steatohepatitis. Given that the pathophysiology of MASLD is incompletely understood, identifying therapeutic targets and optimizing treatment strategies are crucial for addressing this severe condition.</p><p><strong>Methods: </strong>Mendelian randomization (MR) analysis was conducted using two genome-wide association study datasets: a European meta-analysis (8,434 cases; 770,180 controls) and an additional study (3,954 cases; 355,942 controls), identifying therapeutic targets for MASLD. Of 4302 drug-target genes, 2,664 genetic instrument variables were derived from cis-expression quantitative trait loci (cis-eQTLs). Colocalization analyses assessed shared causal variants between MASLD-associated single nucleotide polymorphisms and eQTLs. Using the drug target gene cis-eQTL of liver tissue from the genotype-tissue expression project, we performed MR and summary MR to validate the significance of the gene results of the blood eQTL MR. RNA-sequencing data from liver biopsies were validated using immunohistochemistry and quantitative polymerase chain reaction (qPCR) tests to confirm gene expression findings.</p><p><strong>Result: </strong>MR analysis across both datasets identified significant MR associations between MASLD and two drug targets-milk fat globule-EGF factor 8 (MFGE8) (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.85-0.94; P = 2.15 × 10^-6) and cluster of differentiation 33 (CD33) (OR 1.17, 95% CI 1.10-1.25; P = 1.39 × 10^-6). Both targets exhibited strong colocalization with MASLD. Genetic manipulation indicating MFGE8 activation and CD33 inhibition did not increase the risk for other metabolic disorders. RNA-sequencing, qPCR, and immunohistochemistry validation demonstrated consistent differential expressions of MFGE8 and CD33 in MASLD.</p><p><strong>Conclusion: </strong>CD33 inhibition can reduce MASLD risk, while MFGE8 activation may offer therapeutic benefits for MASLD treatment.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"113"},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719781","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":"Changes in non-high-density lipoprotein to high-density lipoprotein ratio (NHHR) and cardiovascular disease: insights from CHARLS.","authors":"Bingxue Wang, LiYing Li, Ying Tang, Ting Lin, Jing Wu, Guoqi Wang, Xingwu Ran","doi":"10.1186/s12944-025-02536-3","DOIUrl":"10.1186/s12944-025-02536-3","url":null,"abstract":"<p><strong>Background: </strong>The established association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and cardiovascular disease (CVD) risk has been well-documented. Nevertheless, the relationship between changes in NHHR and CVD events remains to be elucidated. The present study aims to clarify the correlation between NHHR change patterns and the incidence of CVD across a broad population.</p><p><strong>Methods: </strong>The current study recruited participants from the China Health and Retirement Longitudinal Study (CHARLS). The NHHR index was calculated using the formula: NHHR = (TC-HDL-c)/HDL-c. Temporal changes in NHHR were assessed with latent profile analysis, and cumulative NHHR was also evaluated. Multivariable Cox proportional hazards regression models and multivariate-adjusted restricted cubic spline (RCS) analyses were employed to examine the association between the NHHR index and incident CVD.</p><p><strong>Results: </strong>A total of 4,629 individuals were recruited for the study. The average age of the participants was 57.47 years, with 53.7% being female. Over the follow-up period, 879 cases of CVD were documented. Compared to participants in the lowest tertile, those in the highest tertile for both baseline NHHR and cumulative NHHR exhibited a significantly increased risk of CVD, with adjusted hazard ratios (HRs) of 1.43 (95% confidence interval [CI]: 1.21-1.70) and 1.45 (95% CI: 1.23-1.72), respectively. Participants classified in Class 2 demonstrated a 27% higher risk of CVD, while those in Class 3 showed a 41% greater risk compared to the Class 1 group. Further analysis revealed that this relationship was linear. Stratified analyses corroborated the primary findings.</p><p><strong>Conclusion: </strong>Baseline NHHR, cumulative NHHR, and changes in NHHR are significantly associated with an increased risk of CVD among individuals aged 45 years and older, thereby confirming their potential as valuable tools for risk stratification in CVD.</p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"24 1","pages":"112"},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710542","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}