Journal of Lipid Research最新文献

Low-density Lipoprotein Regulates Intestinal Stem Cell Homeostasis via PPAR Pathway. 低密度脂蛋白通过PPAR通路调控肠道干细胞稳态。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-14 DOI: 10.1016/j.jlr.2025.100826

Ruicheng Shi, Wei Lu, Zhiming Zhao, Bo Wang

引用次数: 0

Stearoyl-CoA Desaturase 1 deficiency drives saturated lipid accumulation and increases liver and plasma acylcarnitines. 硬脂酰辅酶a去饱和酶1缺乏驱动饱和脂质积累，增加肝脏和血浆酰基肉碱。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-09 DOI: 10.1016/j.jlr.2025.100824

Mugagga Kalyesubula, Helaina Von Bank, Jessica W Davidson, Maggie S Burhans, Madelaine M Becker, Ahmed Aljohani, Judith Simcox, James M Ntambi

{"title":"Stearoyl-CoA Desaturase 1 deficiency drives saturated lipid accumulation and increases liver and plasma acylcarnitines.","authors":"Mugagga Kalyesubula, Helaina Von Bank, Jessica W Davidson, Maggie S Burhans, Madelaine M Becker, Ahmed Aljohani, Judith Simcox, James M Ntambi","doi":"10.1016/j.jlr.2025.100824","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100824","url":null,"abstract":"Stearoyl-CoA desaturase-1 (SCD1) is a critical regulator of lipogenesis that catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleate (18:1n-9) and palmitoleate (16:1n-7) from saturated fatty acids (SFA), stearoyl-CoA (18:0) and palmitoyl-CoA (16:0), respectively. Elevated SCD1 expression and its products are associated with obesity, metabolic dysfunction-associated steatotic liver disease, insulin resistance, and cancer. Conversely, Scd1 deficiency diminishes de novo lipogenesis and protects mice against adiposity, hepatic steatosis, and hyperglycemia. Yet, the comprehensive impact of Scd1 deficiency on hepatic and circulating lipids remains incompletely understood. To further delineate the effects of SCD1 on lipid metabolism, we employed lipidomics on the liver from mice under a lipogenic high carbohydrate, very low-fat diet. We found that Scd1 deficiency leads to an accumulation of saturated lipids and an increase in hepatic and plasma acylcarnitines. Remarkably, transgenic replenishment of de novo oleate synthesis by human SCD5 in the liver of Scd1-deficient mice not only restored hepatic lipid desaturation levels but also attenuated acylcarnitine accumulation, highlighting the distinct role of SCD1 and oleate in regulating intracellular lipid homeostasis.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100824"},"PeriodicalIF":5.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI. 脑外伤后过氧化物酶体醚-甘油磷脂合成失调。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-07 DOI: 10.1016/j.jlr.2025.100821

Amir Mehrabani-Tabari, Nivedita Hegdekar, Sabrina Bustos, Yulemni Morel, Yuanyuan Ji, Sazia Arefin Kachi, Olivia Pettyjohn-Robin, Sagarina Thapa, Maya Bhattiprolu, Marta M Lipinski, Jace W Jones, Chinmoy Sarkar

{"title":"Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI.","authors":"Amir Mehrabani-Tabari, Nivedita Hegdekar, Sabrina Bustos, Yulemni Morel, Yuanyuan Ji, Sazia Arefin Kachi, Olivia Pettyjohn-Robin, Sagarina Thapa, Maya Bhattiprolu, Marta M Lipinski, Jace W Jones, Chinmoy Sarkar","doi":"10.1016/j.jlr.2025.100821","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100821","url":null,"abstract":"Ether-glycerophospholipids (ether-GPs), the ether bond- (- O -) containing glycerophospholipids are major components of brain lipidome. Ether-GPs play a crucial role in regulating neuronal function, and their deficiency has been implicated in many neurodegenerative diseases. However, how they are affected after traumatic brain injury (TBI) is not known. Our data demonstrate a significant decrease in ether-GPs abundance in the mouse cortex following controlled cortical impact (CCI) induced TBI. This is at least in part due to the impairment of peroxisomal ether-GP synthesis in the mouse brain after TBI. We detected dysregulation of peroxisomal ether-GPs synthesizing enzymes - glyceronephosphate-O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the injured mouse brains. Our data demonstrate a significant decline in GNPAT level in the peroxisomal fraction and a marked accumulation of AGPS in the cytosol of mouse cortices after TBI. To restore ether-GPs level in the injured brain, we treated TBI mice with an ether-GP precursor - 1-O-octadecylglycerol (OAG) to bypass peroxisomal ether-GPs synthesizing steps. OAG partially restored the levels of several ether-GPs, attenuated inflammatory cytokine expression and improved their functional recovery after TBI. Taken together, our data demonstrate that decline in ether-GPs abundance after TBI is at least in part due to the impairment in peroxisomal ether-GPs synthesis and that restoration of ether-GPs by OAG treatment can improve TBI outcomes.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100821"},"PeriodicalIF":5.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global deletion of COX-2 Attenuates Hepatic Inflammation but Impairs Metabolic Homeostasis in Diet-Induced Obesity. COX-2的整体缺失减轻了肝脏炎症，但损害了饮食性肥胖的代谢稳态。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-07 DOI: 10.1016/j.jlr.2025.100823

Jeyakumar Balakrishnan, Cyrus Desouza, Rishikesh Thakare, Yazen Alnouti, Viswanathan Saraswathi

{"title":"Global deletion of COX-2 Attenuates Hepatic Inflammation but Impairs Metabolic Homeostasis in Diet-Induced Obesity.","authors":"Jeyakumar Balakrishnan, Cyrus Desouza, Rishikesh Thakare, Yazen Alnouti, Viswanathan Saraswathi","doi":"10.1016/j.jlr.2025.100823","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100823","url":null,"abstract":"The role of cyclooxygenase-2 (COX-2), a well-known pharmacological target for attenuating inflammation, in regulating obesity and its co-morbidities remains unclear. We sought to determine the role of COX-2 in modulating metabolic inflammation and systemic metabolic homeostasis in obesity. Male wild type (WT) and COX-2 knock-out (KO) mice were fed a chow diet (CD) or a high fat diet (HF, 45% fat) for 13 wk. While the body weight gain did not alter, the visceral adipose tissue (VAT) mass was significantly higher in KO-HF mice compared to WT-HF mice. Plasma triglycerides and total cholesterol levels were higher in KO-HF mice compared to WT-HF mice. Total body fat mass was higher with a concomitant reduction in lean mass in KO-HF mice compared to WT-HF mice. Paradoxically, hepatic steatosis was reduced in KO-HF mice. While liver triglycerides were reduced, the liver cholesterol was increased in KO-HF mice. Bile acids and markers of cholesterol biosynthesis were unaltered between WT-HF and KO-HF groups. The mRNA and/or protein levels of autophagy markers were significantly decreased in KO-HF mice compared to WT-HF mice, indicating that a reduction in autophagy may increase cholesterol levels in these mice. The liver inflammatory markers were significantly increased only in WT mice fed a HF diet but not in KO-HF fed mice compared to their respective controls. VAT showed a reduction in inflammatory markers in spite of an increase in adiposity. These data suggest that despite being effective in attenuating the inflammatory processes, inhibition of COX-2 exerts undesirable consequences on metabolic homeostasis.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100823"},"PeriodicalIF":5.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance. Plaat1缺乏会降低心磷脂含量，损害运动耐受性。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-07 DOI: 10.1016/j.jlr.2025.100822

Ashkan Hashemi, Ming Rong Liu, John Z Chan, Antonia N Berdeklis, Alex D Cocco, Michelle V Tomczewski, Douglas Strathdee, Ken D Stark, Robin E Duncan

{"title":"Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance.","authors":"Ashkan Hashemi, Ming Rong Liu, John Z Chan, Antonia N Berdeklis, Alex D Cocco, Michelle V Tomczewski, Douglas Strathdee, Ken D Stark, Robin E Duncan","doi":"10.1016/j.jlr.2025.100822","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100822","url":null,"abstract":"Phospholipase A and acyltransferase 1 (PLAAT1) catalyzes O-transacylase, N-transacylase and phospholipase A1/2 reactions. We have demonstrated that PLAAT1 has O-transacylase activity in vitro using phosphatidylcholine as an acyl donor, and monolysocardiolipin (MLCL) as an acyl acceptor, generating cardiolipin. However, a role for PLAAT1 in cardiolipin regulation in vivo has not yet been reported. We generated Plaat1-deficient (Plaat1-/-) mice and studied males and females for gross morphological differences, food intakes, respiratory gas exchange, total energy expenditure, and voluntary activity. We also evaluated cardiac cardiolipin contents, levels of mitochondrial proteins, and exercise capacity. Sex-matched Plaat1-/- mice had highly similar body weights to their wildtype (Wt) littermates, although male Plaat1-/- mice ate less. Male and female Plaat1-/- hearts were 14.2% and 10.6% smaller, respectively. Cardiac cardiolipin levels were ∼1/3 lower in male and female Plaat1-/- mice compared to their sex-matched Wt littermates, largely due to lower cardiolipin linoleate. Levels of the mitochondrial protein SDHA were 13.8% and 16.3% lower in male and female Plaat1-/- mice, respectively. Both male and female Plaat1-/- mice had significantly lower oxygen consumption, carbon dioxide production, and total energy expenditure, and male Plaat1-/- mice had lower rearing activity than their sex-matched Wt littermates. While other measures of voluntary activity, including locomotion and ambulation did not differ significantly between genotypes, both males and females had reduced exercise tolerance. This work demonstrates a critical role for PLAAT1 in cardiac cardiolipin content and the regulation of energy metabolism and exercise tolerance in vivo.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100822"},"PeriodicalIF":5.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosome-derived miR-548ag drives hepatic lipid accumulation via upregulating FASN through inhibition of DNMT3B. 外泌体来源的miR-548ag通过抑制DNMT3B上调FASN来驱动肝脏脂质积累。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-06 DOI: 10.1016/j.jlr.2025.100818

Xiaolong Chu, Yanting Hou, Chaoling Peng, Wei Li, Maodi Liang, Jin Mei, Meiyu Qian, Juan Wang, Shibo Xu, Yidan Jiang, Xin Wen, Yao Chen, Fangyuan Yuan, Jianxin Xie, Cuizhe Wang, Jun Zhang

{"title":"Exosome-derived miR-548ag drives hepatic lipid accumulation via upregulating FASN through inhibition of DNMT3B.","authors":"Xiaolong Chu, Yanting Hou, Chaoling Peng, Wei Li, Maodi Liang, Jin Mei, Meiyu Qian, Juan Wang, Shibo Xu, Yidan Jiang, Xin Wen, Yao Chen, Fangyuan Yuan, Jianxin Xie, Cuizhe Wang, Jun Zhang","doi":"10.1016/j.jlr.2025.100818","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100818","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. This study investigates the role of serum miR-548ag in regulating lipid metabolism and its contribution to MASLD in obesity. We found that miR-548ag levels were significantly elevated in the serum of both obese and MASLD patients, and positively correlated with body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC), LDL, HDL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Additionally, miR-548ag expression was significantly higher in the liver and abdominal adipose tissue of obese individuals compared to those of normal weight. In vitro studies in HepG2 and L02 cells, along with previous findings, demonstrated that miR-548ag promotes fatty acid synthase (FASN) expression by inhibiting DNA methyltransferase 3B (DNMT3B), thereby enhancing lipid synthesis. This was confirmed in two mouse models: one with tail vein injections of miR-548ag mimic/inhibitor adeno-associated viruses, and another with tail vein injections of exosomes from serum of normal-weight and obese individuals. Both models showed that miR-548ag upregulated FASN through DNMT3B inhibition, leading to increased lipid synthesis and larger hepatic lipid droplets, effects that were reversed by miR-548ag inhibition. Taken together, elevated miR-548ag expression in obesity enhances hepatic lipid synthesis by targeting DNMT3B to upregulate FASN, contributing to the development of MASLD.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100818"},"PeriodicalIF":5.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipoprotein (a) integrates monocyte-mediated thrombosis and inflammation in atherosclerotic cardiovascular disease. 脂蛋白(a)在动脉粥样硬化性心血管疾病中整合了单核细胞介导的血栓和炎症。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-05 DOI: 10.1016/j.jlr.2025.100820

Robert S Rosenson, Ashley M Tate, Olga G Grushko, Dilna Damodaran, Qinzhong Chen, Michael Boffa, Marlys Koschinsky, Jagat Narula, Sascha N Goonewardena

{"title":"Lipoprotein (a) integrates monocyte-mediated thrombosis and inflammation in atherosclerotic cardiovascular disease.","authors":"Robert S Rosenson, Ashley M Tate, Olga G Grushko, Dilna Damodaran, Qinzhong Chen, Michael Boffa, Marlys Koschinsky, Jagat Narula, Sascha N Goonewardena","doi":"10.1016/j.jlr.2025.100820","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100820","url":null,"abstract":"Background: Elevated levels of lipoprotein (a) [Lp(a)], an apolipoprotein B particle, are causally linked to atherosclerotic cardiovascular disease (ASCVD). Lp(a) is thought to promote ASCVD through multiple mechanisms, including its effects on cholesterol transport, inflammation, and thrombosis.Objective: Define the mechanisms that integrate Lp(a)-mediated cholesterol accumulation, inflammation, and thrombosis.Methods: In this study, we employed systems biology approaches, including proteomics, transcriptomics, and mass cytometry, to define the immune cellular and molecular phenotypes in ASCVD subjects with high and low Lp(a) levels and the molecular mechanisms through which Lp(a) mediates monocyte-driven inflammation and thrombosis.Results: In 64 stable ASCVD subjects (41 with high Lp(a) [median Lp(a) 228.7 nmol/L] and 23 with low Lp(a) [median Lp(a) 17.8 nmol/L]), we found that circulating markers of inflammation (CCL28, IL-17D) and vascular dysfunction (tissue factor [TF]; 6.4 vs 5.7 normalized protein expression (NPX); p=0.01) were elevated in subjects with high Lp(a) levels compared with those with low Lp(a) levels. Although total monocyte and hsCRP levels were similar between the groups, CD14+ monocytes from ASCVD subjects with an elevated Lp(a) were primed and expressed more TF at baseline and in response to stress. Mechanistically, we found that Lp(a) itself can activate monocytes through Toll-like receptor 2 (TLR2) and nuclear factor kappa B (NFκB) signaling, driving both the induction of TF and TF activity.Conclusions: Overall, these studies are the first to link Lp(a) to monocyte-mediated inflammation and thrombosis. They demonstrate a novel mechanism through TLR2, NFκB, and monocyte TF by which Lp(a) amplifies immunothrombotic risk.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100820"},"PeriodicalIF":5.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Specific FAHFAs Predict Worsening Glucose Tolerance in Non-Diabetic Relatives of People with Type 2 Diabetes. 特异性fafas预测2型糖尿病患者非糖尿病亲属糖耐量恶化

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-05 DOI: 10.1016/j.jlr.2025.100819

Ismail Syed, Ken Sluis, Pratik Aryal, Zachary Solomon, Rucha Patel, Srihari Konduri, Dionicio Siegel, Ulf Smith, Barbara B Kahn

{"title":"Specific FAHFAs Predict Worsening Glucose Tolerance in Non-Diabetic Relatives of People with Type 2 Diabetes.","authors":"Ismail Syed, Ken Sluis, Pratik Aryal, Zachary Solomon, Rucha Patel, Srihari Konduri, Dionicio Siegel, Ulf Smith, Barbara B Kahn","doi":"10.1016/j.jlr.2025.100819","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100819","url":null,"abstract":"There is a growing need for early biomarkers for Type 2 diabetes (T2D). Fatty-Acid-Hydroxy-Fatty-Acids (FAHFAs) are bioactive lipids with >580 regioisomers in human tissues. FAHFAs such as Palmitic Acid Hydroxy Stearic Acids (PAHSAs) are anti-diabetic and anti-inflammatory. PAHSA concentrations in human serum and adipose tissue strongly correlate with insulin-sensitivity. Since PAHSAs and palmitic acid hydroxy oleic acids (PAHOAs) are among the most abundant FAHFAs in human serum, we investigated whether they predict worsening glucose tolerance in first-degree relatives of people with T2D. All participants had normal glucose tolerance (NGT) at baseline; 27 remained NGT (NGT-NGT) and 21 developed impaired glucose tolerance (NGT-IGT). In NGT-NGT, total PAHSA and PAHSA regioisomer concentrations were unchanged from baseline to follow up, while in NGT-IGT participants, most PAHSA regioisomers decreased. The initial total PAHSAs, 5-PAHSA, and 9-PAHSA, and changes in these correlated inversely with worsening glucose tolerance. Low total PAHSA concentrations at baseline and the decrease in total PAHSAs, 5-PAHSAs and 9-PAHSAs over time predicted IGT independent of initial BMI or %body fat, change in BMI or %body fat, initial fasting glucose, fasting insulin or triglyceride/HDL ratio. In contrast, baseline and follow up total PAHOA and PAHOA regioisomer levels were higher in NGT-IGT than NGT-NGT and some PAHOA regioisomers increased during follow up in NGT-IGT. Higher initial total PAHOAs predicted IGT independent of the same clinical variables. Thus, lower serum PAHSAs and higher PAHOAs predict worsening glucose tolerance/IGT independent of BMI, %body fat or change in these parameters even in lean, relatively young people.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100819"},"PeriodicalIF":5.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Introduction of a Lipidomics Scoring System for data quality assessment. 脂质组学评分系统的介绍，用于数据质量评估。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-04-30 DOI: 10.1016/j.jlr.2025.100817

Nils Hoffmann, Robert Ahrends, Erin S Baker, Kim Ekroos, Xianlin Han, Michal Holčapek, Gerhard Liebisch, Markus R Wenk, Yu Xia, Harald C Köfeler

{"title":"Introduction of a Lipidomics Scoring System for data quality assessment.","authors":"Nils Hoffmann, Robert Ahrends, Erin S Baker, Kim Ekroos, Xianlin Han, Michal Holčapek, Gerhard Liebisch, Markus R Wenk, Yu Xia, Harald C Köfeler","doi":"10.1016/j.jlr.2025.100817","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100817","url":null,"abstract":"The scientific field of lipidomics has shown a constantly growing publication number in recent years, which is accompanied by an increasing need for quality standards. While the official shorthand nomenclature of lipids is a first and important step towards a reporting quality tool, an additional point score would reflect the quality of reported data at an even more detailed granularity. Thus, we propose a lipidomics scoring scheme that considers all the different layers of analytical information to be obtained by mass spectrometry, chromatography, and ion mobility spectrometry and awards scoring points for each of them. Furthermore, the scoring scheme is integrated with the annotation levels as proposed by the official shorthand nomenclature, with a point score, which roughly correlates with the annotated compound details. The merit of such a scoring system is the fact that it abstracts evidence for structural information into a number, which gives even the non-lipidomics expert an idea about the reporting, and by extension, data quality at first glance. Additionally, it could serve as an aid for internal quality control and for data quality assessment in the peer review process.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100817"},"PeriodicalIF":5.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circulating lipidome underpins gender differences in the pathogenesis of type 2 diabetes. 循环脂质组支持2型糖尿病发病机制的性别差异。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-04-26 DOI: 10.1016/j.jlr.2025.100816

Madhusmita Rout, Oliver Fiehn, Dharambir K Sanghera

{"title":"Circulating lipidome underpins gender differences in the pathogenesis of type 2 diabetes.","authors":"Madhusmita Rout, Oliver Fiehn, Dharambir K Sanghera","doi":"10.1016/j.jlr.2025.100816","DOIUrl":"https://doi.org/10.1016/j.jlr.2025.100816","url":null,"abstract":"Metabolic alterations in human lipidome significantly impact various chronic diseases including type 2 diabetes (T2D). However, epidemiology and clinical studies have yet to identify clinically meaningful lipid markers for T2D. Fatty acids (FAs) are the backbone of lipid species. However, conflicting results on the essential FAs including omega 3 and omega 6 in the development of metabolic diseases urge deeper evaluations of diverse clinical cohorts including underrepresented populations. This study investigated the lipidomics profiles of 3000 individuals from a well-characterized cohort of Asian Indians. Untargeted lipidomic profiles were created using blood samples applying reversed-phase liquid chromatography-accurate mass tandem mass spectrometry. Free FAs and lysophosphatidylcholines (LPC) were upregulated, while sphingomyelin (SM) and phosphatidylcholines (PC) were decreased in T2D. We observed a significant increase of essential FAs -FA20:4 (AA), FA20:5 (EPA), and FA22:6 (DHA) in T2D after adjusting for age, gender, and BMI. However, most ω-3 and ω-6 FAs were reduced by 2 to 6-fold in obesity in both genders. We also observed gender differences in age-associated lipid patterns in which cholesterol sulfate and LPC 22:6 were elevated in all age groups in men, but LPC 22:6 rapidly increased after menopause in women, and SMs increased in men after 40 years. Machine learning analysis identified long-chain FAs, ether-based LPCs, and clinical risk scores among the most informative features associated with T2D. Our study identified lipidomic markers that could be potential mediators of T2D and obesity. Their patterns may underpin sex differences in the pathogenesis of metabolic and cardiovascular diseases.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100816"},"PeriodicalIF":5.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0