Journal of Lipid Research最新文献_第5页

Deep sphingolipidomic and metabolomic analyses of ceramide synthase 2 null mice reveal complex pathway-specific effects. 神经酰胺合成酶2缺失小鼠的深层鞘脂组学和代谢组学分析揭示了复杂的通路特异性作用。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-29 DOI: 10.1016/j.jlr.2025.100832

Jeongah Oh, Sneha Muralidharan, Qing Zhao, Johannes Scholz, Iris D Zelnik, Shani Blumenreich, Tammar Joseph, Tamir Dingjan, Pradeep Narayanaswamy, Hyungwon Choi, Heiko Hayen, Federico Torta, Anthony H Futerman

{"title":"Deep sphingolipidomic and metabolomic analyses of ceramide synthase 2 null mice reveal complex pathway-specific effects.","authors":"Jeongah Oh, Sneha Muralidharan, Qing Zhao, Johannes Scholz, Iris D Zelnik, Shani Blumenreich, Tammar Joseph, Tamir Dingjan, Pradeep Narayanaswamy, Hyungwon Choi, Heiko Hayen, Federico Torta, Anthony H Futerman","doi":"10.1016/j.jlr.2025.100832","DOIUrl":"10.1016/j.jlr.2025.100832","url":null,"abstract":"The sphingolipidome contains thousands of structurally distinct sphingolipid (SL) species. This enormous diversity is generated by the combination of different long-chain bases (LCBs), N-acyl chains and head groups. In mammals, LCBs are N-acylated with different fatty acids (from C14 to C32, with different degrees of saturation) by six ceramide synthases (CerS1-6) to generate dihydroceramides (DHCer), with each CerS exhibiting specificity toward acyl-Coenzyme As of defined chain length. CerS2 synthesizes very-long chain dihydroceramide, and mice in which CerS2 has been deleted display a number of pathologies. We now expand previous analyses of the mouse sphingolipidome by examining 259 individual SL species in 18 different tissues, building an extensive SL tissue atlas of WT and CerS2 null mice. Although many of the changes in SL levels were similar to those reported earlier, a number of unexpected findings in CerS2 null mouse tissues were observed, such as the decrease in ceramide 1-phosphate levels in the brain, the increase in C26-SL levels in the lung, and no changes in levels of ceramides containing t18:0-LCBs (phytosphinganine). Furthermore, analysis of levels of other metabolites revealed changes in at least six major metabolic pathways, including some that impinge upon the SL metabolism. Together, these data highlight the complex changes that occur in the lipidome and metabolome upon depletion of CerS2, indicating how sphingolipids are connected to many other pathways and that care must be taken when assigning a relationship between tissue pathology and one or other specific SL species.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100832"},"PeriodicalIF":5.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191908","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}

引用次数: 0

Mitochondrial calcium uniporter is required for thermogenic adaptation mediated by reactive oxygen species signaling. 活性氧信号介导的热适应需要线粒体钙单转运体。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-29 DOI: 10.1016/j.jlr.2025.100834

Suji Kim, Seung-Kuy Cha, Kyu-Sang Park, Jun Namkung

{"title":"Mitochondrial calcium uniporter is required for thermogenic adaptation mediated by reactive oxygen species signaling.","authors":"Suji Kim, Seung-Kuy Cha, Kyu-Sang Park, Jun Namkung","doi":"10.1016/j.jlr.2025.100834","DOIUrl":"10.1016/j.jlr.2025.100834","url":null,"abstract":"Mitochondrial Ca2+ influx via mitochondrial calcium uniporter (MCU) accelerates mitochondrial biogenesis and energy metabolism. Nevertheless, the molecular mechanism of MCU-dependent mitochondrial activation and thermogenesis in thermogenic adipose tissues remains elusive. In this study, we demonstrate that MCU governs mitochondrial functions in brown and beige adipocytes via the formation of mitochondrial reactive oxygen species (mtROS). Mice with a brown adipose tissue-specific Mcu knockout (Mcu BKO) mice exhibited decreased oxygen consumption and heat production, accompanied by downregulation of genes related to β-oxidation and thermogenesis. Furthermore, Mcu BKO mice, exhibiting a reduction in mtROS, showed defective thermogenic responses to cold exposure or β-adrenergic stimulation. Downregulation of thermogenic genes including Ucp1 in Mcu BKO mice can be rescued by exogenous ROS through AMP-activated protein kinase (AMPK) activation. Collectively, our findings suggest that MCU modulates mtROS-mediated mitonuclear signaling in thermogenic adipocytes.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100834"},"PeriodicalIF":5.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191925","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}

引用次数: 0

N-aldehyde-modified phosphatidylethanolamines generated by lipid peroxidation are robust substrates of N-acyl phosphatidylethanolamine phospholipase D. 脂质过氧化生成的n -醛修饰磷脂酰乙醇胺是n -酰基磷脂酰乙醇胺磷脂酶D的强大底物。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-21 DOI: 10.1016/j.jlr.2025.100831

Reza Fadaei, Annie C Bernstein, Andrew N Jenkins, Allison G Pickens, Jonah E Zarrow, Abdul-Musawwir Alli-Oluwafuyi, Keri A Tallman, Sean S Davies

{"title":"N-aldehyde-modified phosphatidylethanolamines generated by lipid peroxidation are robust substrates of N-acyl phosphatidylethanolamine phospholipase D.","authors":"Reza Fadaei, Annie C Bernstein, Andrew N Jenkins, Allison G Pickens, Jonah E Zarrow, Abdul-Musawwir Alli-Oluwafuyi, Keri A Tallman, Sean S Davies","doi":"10.1016/j.jlr.2025.100831","DOIUrl":"10.1016/j.jlr.2025.100831","url":null,"abstract":"N-acyl phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) hydrolyzes phosphatidylethanolamines (PEs) where the headgroup nitrogen has been enzymatically modified with acyl chains of four carbons or longer (N-acyl-PEs or NAPEs). The nitrogen headgroup of PE can also be nonenzymatically modified by reactive lipid aldehydes, thus forming N-aldehyde-modified PEs (NALPEs). Some NALPEs such as N-carboxyacyl-PEs are linked to PE via amide bonds similar to NAPEs, but others are linked by imine, pyrrole, or lactam moieties. Whether NAPE-PLD can hydrolyze NALPEs was unknown. We therefore characterized the major NALPE species formed during lipid peroxidation of arachidonic acid and linoleic acid and generated various NALPEs for characterization of their sensitivity to NAPE-PLD hydrolysis by reacting synthesized aldehydes with PE. We found that NAPE-PLD could act on NALPEs of various lengths and linkage types including those derived from PE modified by N-malondialdehyde, N-4-hydroxynonenal, N-4-oxo-nonenal, N-9-keto-12-oxo-dodecenoic acid, and N-15-E2-isolevuglandin. To assess the relative preference of NAPE-PLD for various NALPEs versus its canonical NAPE substrates, we generated a substrate mixture containing roughly equimolar concentrations of seven NALPEs as well as two NAPEs (N-palmitoyl-PE and N-linoleoyl-PE) and measured their rate of hydrolysis. Several NALPE species, including the N-4-hydroxynonenal-PE pyrrole species, were hydrolyzed at a similar rate as N-linoleoyl-PE, and many of the other NALPEs showed intermediate rates of hydrolysis. These results significantly expand the substrate repertoire of NAPE-PLD and suggest that it may play an important role in clearing products of lipid peroxidation in addition to its established role in the biosynthesis of N-acyl-ethanolamines.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100831"},"PeriodicalIF":5.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131996","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}

引用次数: 0

Fentanyl-induced transformations in composition of lipid droplets in central nervous system cells revealed by ramanomics. 芬太尼诱导中枢神经系统细胞脂滴组成的转变

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-19 DOI: 10.1016/j.jlr.2025.100827

Rahul K Das, Andrey N Kuzmin, Artem Pliss, Supriya D Mahajan, Shobha Shukla, Paras N Prasad

{"title":"Fentanyl-induced transformations in composition of lipid droplets in central nervous system cells revealed by ramanomics.","authors":"Rahul K Das, Andrey N Kuzmin, Artem Pliss, Supriya D Mahajan, Shobha Shukla, Paras N Prasad","doi":"10.1016/j.jlr.2025.100827","DOIUrl":"10.1016/j.jlr.2025.100827","url":null,"abstract":"Quantitative characterization of the transformations of subcellular molecular environment in response to fentanyl exposure in human microglia and astrocytes is warranted to provide insight into the regulation of neuroinflammatory responses and neural survival in the scenario of opiate drug addiction. Cytoplasmic lipid droplets (LD) act as depot for exogeneous hydrophobic molecules, such as fentanyl, which can lead to increased drug accumulation and alteration of their metabolism. In the present work, we have used an emerging Ramanomics technique that combines quantitative microlipid droplets -Raman spectrometry with biomolecular component analysis to unravel fentanyl induced changes in concentrations of phospholipids, sterols, glycogen, sphingomyelin, phosphocholine as well as RNA and proteins, in the LDs of microglia and astrocytes. The clinical relevance of these findings includes the potential to advance understanding of fentanyl's impact on the central nervous system at a molecular level. The observed alterations in lipid droplet composition, including changes in phospholipids, cholesterol esters, and glycogen accumulation, suggest that fentanyl overdose disrupts cellular homeostasis in microglia and astrocytes. This disruption could contribute to neuroinflammatory responses and impaired neural function, which are critical factors in opioid addiction and withdrawal. By utilizing Ramanomics as a noninvasive, real-time analytical tool, we can better assess fentanyl-induced cellular changes, paving the way for improved diagnostic assays and therapeutic strategies for opioid addiction and overdose treatment.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100827"},"PeriodicalIF":5.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119703","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}

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":"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 in %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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271064/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Apolipoprotein A1 deficiency increases macrophage apoptosis and necrotic core development in atherosclerotic plaques in a Bim-dependent manner. 载脂蛋白A1缺乏以Bim依赖的方式增加动脉粥样硬化斑块中巨噬细胞凋亡和坏死核心的发展。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-01 Epub Date: 2025-03-20 DOI: 10.1016/j.jlr.2025.100782

Alexander S Qian, George E G Kluck, Pei Yu, Leticia Gonzalez, Elizabeth Balint, Bernardo L Trigatti

{"title":"Apolipoprotein A1 deficiency increases macrophage apoptosis and necrotic core development in atherosclerotic plaques in a Bim-dependent manner.","authors":"Alexander S Qian, George E G Kluck, Pei Yu, Leticia Gonzalez, Elizabeth Balint, Bernardo L Trigatti","doi":"10.1016/j.jlr.2025.100782","DOIUrl":"10.1016/j.jlr.2025.100782","url":null,"abstract":"In advanced atherosclerotic lesions, macrophage apoptosis contributes to plaque progression and the formation of necrotic cores, rendering plaques vulnerable to rupture. The proapoptotic protein B-cell lymphoma 2 [Bcl-2] interacting mediator of cell death (Bim) plays a crucial role in mediating apoptosis in macrophages under prolonged endoplasmic reticulum stress. HDL has been shown to suppress macrophage apoptosis induced by endoplasmic reticulum stressors. To investigate the impact of apolipoprotein A1 (ApoA1) deficiency, associated with reduced HDL levels, on necrotic core growth and plaque apoptosis, we introduced ApoA1 deficiency into low-density lipoprotein receptor (LDLR) knockout mice and fed them a high-fat diet for 10 weeks. ApoA1-deficient Ldlr KO mice developed advanced plaques characterized by large necrotic cores, increased apoptosis, and elevated Bim expression in macrophages within the plaques. To assess whether deletion of Bim could mitigate this development, mice underwent bone marrow transplantation with bone marrow from either Bim-deficient mice or from mice with a deletion of myeloid-derived Bim driven by LyzM-cre. Inhibiting Bim in all bone marrow-derived cells led to leukocytosis, reductions in plasma cholesterol and triglyceride levels, and decreased plaque apoptosis, necrotic core, and plaque sizes in ApoA1 and Ldlr double-KO mice but not in Ldlr KO mice. Likewise, conditional deletion of Bim in the myeloid compartment of ApoA1 and Ldlr double-KO mice also reduced apoptosis, necrotic core sizes, and plaque sizes, without inducing leukocytosis or lowering plasma cholesterol levels. These findings suggest that ApoA1 deficiency triggers apoptosis in myeloid cells through a Bim-dependent pathway, significantly contributing to the development of necrotic cores and the progression of atherosclerotic plaques.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100782"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692651","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}

引用次数: 0

Serum and plasma sphingolipids as biomarkers of chemotherapy-induced cardiotoxicity in female patients with breast cancer. 血清和血浆鞘脂作为女性乳腺癌患者化疗诱导的心脏毒性的生物标志物。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-01 Epub Date: 2025-04-05 DOI: 10.1016/j.jlr.2025.100798

Samia Mohammed, Andreas P Kalogeropoulos, Victoria Alvarado, Michelle Weisfelner-Bloom, Christopher J Clarke

{"title":"Serum and plasma sphingolipids as biomarkers of chemotherapy-induced cardiotoxicity in female patients with breast cancer.","authors":"Samia Mohammed, Andreas P Kalogeropoulos, Victoria Alvarado, Michelle Weisfelner-Bloom, Christopher J Clarke","doi":"10.1016/j.jlr.2025.100798","DOIUrl":"10.1016/j.jlr.2025.100798","url":null,"abstract":"Although effective as a chemotherapeutic, the utility of Doxorubicin (Dox) is hampered by cardiotoxicity. Despite this, the ability to predict and guide monitoring of patients receiving Dox is hampered by a lack of effective biomarkers to identify susceptible patients and detect early signs of subclinical cardiotoxicity. Based on their well-established roles in the response to Dox and other chemotherapies, we performed a retrospective analysis of serum and plasma sphingolipids (SLs) from female patients with breast cancer (BC) undergoing anthracycline-containing therapy, correlating with cardiac parameters assessed by echocardiography. Results showed substantial changes in both plasma and serum SL species during therapy including ceramide (Cer), deoxydihydroCer, and dihydrosphingosine with reversion toward baseline after treatment. Linear mixed-effects model analysis revealed that baseline levels of a number of SLs correlated with adverse cardiac outcomes. Here, serum sphingosine-1-phosphate (S1P), dihydroS1P, and plasma Cer performed comparably to the prognostic value of pro-NT-BNP, an established biomarker of cardiotoxicity. Intriguingly, while pro-NT-BNP had no predictive value at mid- and post-therapy timepoints, serum S1P and dihydroS1P, and plasma Cer levels showed a correlation with adverse outcomes, particularly at the post-therapy timepoint. Finally, analysis of plasma and serum C16:C24-Cer ratios-previously linked with adverse cardiac outcomes-showed no correlation in the context of chemotherapy treatment. Overall, this pilot study provides initial evidence that plasma and serum SLs may have benefits as both prognostic and diagnostic biomarkers for female BC patients undergoing anthracycline-containing chemotherapy. Consequently, diagnostic SL measurements-recently implemented for metabolic-associated cardiac disorders-could have wider utility.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100798"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795672","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}

引用次数: 0

Diet-induced obesity dampens the temporal oscillation of hepatic mitochondrial lipids. 饮食引起的肥胖抑制肝脏线粒体脂质的时间振荡。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1016/j.jlr.2025.100790

Rashi Jain, Rajprabu Rajendran, Sona Rajakumari

{"title":"Diet-induced obesity dampens the temporal oscillation of hepatic mitochondrial lipids.","authors":"Rashi Jain, Rajprabu Rajendran, Sona Rajakumari","doi":"10.1016/j.jlr.2025.100790","DOIUrl":"10.1016/j.jlr.2025.100790","url":null,"abstract":"Mitochondria play a pivotal role in energy homeostasis and regulate several metabolic pathways. The inner and outer membrane of mitochondria comprises unique lipid composition and proteins that are essential to form electron transport chain complexes, orchestrate oxidative phosphorylation, β-oxidation, ATP synthesis, etc. As known, diet-induced obesity affects mitochondrial function, dynamics, and mitophagy, which are governed by circadian clock machinery. Though DIO impairs the interplay between circadian oscillation and lipid metabolism, the impact of DIO on mitochondrial membrane lipid composition and their temporal oscillation is unknown. Thus, we investigated the diurnal oscillation of liver mitochondrial lipidome at various Zeitgeber times using quantitative lipidomics. Our data suggested that obesity disrupted lipid accumulation profiles and diminished the oscillating lipid species in the hepatic mitochondria. Strikingly, HFD manifested a more homogenous temporal oscillation pattern in phospholipids regardless of possessing different fatty acyl-chain lengths and degrees of unsaturation. In particular, DIO impaired the circadian rhythmicity of phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine, and ether-linked phosphatidyl ethanolamine. Also, DIO altered the rhythmic profile of PE/PC, ePE/PC, PS/PC ratio, and key proteins related to mitochondrial function, dynamics, and quality control. Since HFD dampened lipid oscillation, we examined whether the diurnal oscillation of mitochondrial lipids synchronized with mitochondrial function. Also, our data emphasized that acrophase of mitochondrial lipids synchronized with increased oxygen consumption rate and Parkin levels at ZT16 in chow-fed mice. Our study revealed that obesity altered the mitochondrial lipid composition and hampered the rhythmicity of mitochondrial lipids, oxygen consumption rate, and Parkin levels in the liver.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100790"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780303","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}

引用次数: 0

Statin effects on the lipidome: Predicting statin usage and implications for cardiovascular risk prediction. 他汀类药物对脂质组的影响：预测他汀类药物的使用及其对心血管风险预测的影响。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-01 Epub Date: 2025-04-10 DOI: 10.1016/j.jlr.2025.100800

Changyu Yi, Kevin Huynh, Yvette Schooneveldt, Gavriel Olshansky, Amy Liang, Tingting Wang, Habtamu B Beyene, Aleksandar Dakic, Jingqin Wu, Michelle Cinel, Natalie A Mellett, Gerald F Watts, Joseph Hung, Jennie Hui, John Beilby, Joanne E Curran, John Blangero, Eric K Moses, John Simes, Andrew M Tonkin, Leonard Kritharides, David Sullivan, Jonathan E Shaw, Dianna J Magliano, Agus Salim, Corey Giles, Peter J Meikle

{"title":"Statin effects on the lipidome: Predicting statin usage and implications for cardiovascular risk prediction.","authors":"Changyu Yi, Kevin Huynh, Yvette Schooneveldt, Gavriel Olshansky, Amy Liang, Tingting Wang, Habtamu B Beyene, Aleksandar Dakic, Jingqin Wu, Michelle Cinel, Natalie A Mellett, Gerald F Watts, Joseph Hung, Jennie Hui, John Beilby, Joanne E Curran, John Blangero, Eric K Moses, John Simes, Andrew M Tonkin, Leonard Kritharides, David Sullivan, Jonathan E Shaw, Dianna J Magliano, Agus Salim, Corey Giles, Peter J Meikle","doi":"10.1016/j.jlr.2025.100800","DOIUrl":"10.1016/j.jlr.2025.100800","url":null,"abstract":"Statin therapy is a highly successful and cost-effective strategy for the prevention and treatment of cardiovascular diseases (CVD). Adjusting for statin usage is crucial when exploring the association of the lipidome with CVD to avoid erroneous conclusions. However, practical challenges arise in real-world scenarios due to the frequent absence of statin usage information. To address this limitation, we demonstrate that statin usage can be accurately predicted using lipidomic data. Using three large population datasets and a longitudinal clinical study, we show that lipidomic-based statin prediction models exhibit high prediction accuracy in external validation. Furthermore, we introduce a re-weighted model, designed to overcome a ubiquitous limitation of prediction models, namely the need for predictor alignment between training and target data. We demonstrated that the re-weighted models achieved comparable prediction accuracy to ad hoc models which use the aligned predictor between training and target data. This innovation holds promise for significantly enhancing the transferability of statin prediction and other 'omics prediction models, especially in situations where predictor alignment is incomplete. Our statin prediction model now allows for the inclusion of statin usage in lipidomic analyses of cohorts even where statin use is not available, improving the interpretability of the resulting analyses.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":"66 5","pages":"100800"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986199","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}

引用次数: 0

S-adenosylmethionine deficit disrupts very low-density lipoprotein metabolism promoting liver lipid accumulation in mice. S-Adenosylmethionine 缺乏会破坏极低密度脂蛋白代谢，促进小鼠肝脏脂质积累

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-05-01 Epub Date: 2025-04-01 DOI: 10.1016/j.jlr.2025.100794

María R Luque-Urbano, David Fernández-Ramos, Fernando Lopitz-Otsoa, Virginia Gutiérrez de Juan, Maider Bizkarguenaga, Lia Castro-Espadas, Uxue Hermoso-Martínez, Lucía Barbier-Torres, Shelly C Lu, Oscar Millet, José M Mato

{"title":"S-adenosylmethionine deficit disrupts very low-density lipoprotein metabolism promoting liver lipid accumulation in mice.","authors":"María R Luque-Urbano, David Fernández-Ramos, Fernando Lopitz-Otsoa, Virginia Gutiérrez de Juan, Maider Bizkarguenaga, Lia Castro-Espadas, Uxue Hermoso-Martínez, Lucía Barbier-Torres, Shelly C Lu, Oscar Millet, José M Mato","doi":"10.1016/j.jlr.2025.100794","DOIUrl":"10.1016/j.jlr.2025.100794","url":null,"abstract":"Hepatic deletion of methionine adenosyltransferase-1a (Mat1a) in mice reduces S-adenosylmethionine (SAMe), a key methyl donor essential for many biological processes, which promotes the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Hyperglycemia and reduced MAT1A expression, along with low SAMe levels, are common in MASLD patients. This study explores how Mat1a-knockout (KO) hepatocytes respond to prolonged high glucose conditions, focusing on glucose metabolism and lipid accumulation. Hepatocytes from methionine adenosyltransferase-1a-knockout (Mat1a-KO) mice were incubated in high glucose conditions overnight, allowing for analysis of key metabolic intermediates and gene expression related to glycolysis, gluconeogenesis, glyceroneogenesis, phospholipid synthesis, and very low density lipoprotein (VLDL) secretion. SAMe deficiency in Mat1a-KO hepatocytes led to reduced protein methyltransferase-1 activity, resulting in increased expression of glycolytic enzymes (glucokinase, phosphofructokinase, and pyruvate kinase) and decreased expression of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase). These alterations led to a reduction in dihydroxyacetone phosphate (DHAP), which subsequently inhibited mammalian target of rapamycin complex 1 (mTORC1) activity. This inhibition resulted in decreased phosphatidylcholine synthesis via the CDP-choline pathway and impaired VLDL secretion, ultimately causing lipid accumulation. Thus, under high glucose conditions, SAMe deficiency in hepatocytes depletes DHAP, inhibits mTORC1 activity, and promotes lipid buildup.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100794"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780307","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}

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