Progress in lipid research最新文献

英文中文

The neurobiology of fatty acids: Metabolism, signaling, and roles in neurodegenerative diseases 脂肪酸的神经生物学：代谢、信号传导和在神经退行性疾病中的作用

IF 13.6 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2026-02-07 DOI: 10.1016/j.plipres.2026.101378

Rocío Rojas, Alicia Pellitero, Betül Arslan, Alberto Pérez-Samartín, Carlos Matute

引用次数: 0

Announcing executive editor team changes 宣布执行编辑团队的变动

IF 13.6 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2026-02-03 DOI: 10.1016/j.plipres.2026.101376

Danielle Descoteaux, Andy Deelen

引用次数: 0

Phospholipids in plant systems: metabolism, regulation and functional insights 磷脂在植物系统：代谢，调节和功能的见解

IF 13.6 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2026-01-30 DOI: 10.1016/j.plipres.2026.101377

Qiong Xiao, Stacy D. Singer, Yuki Nakamura, Guanqun Chen

引用次数: 0

Diacylglycerol kinases: Molecular mechanism of cellular and physiological functions. 二酰基甘油激酶：细胞和生理功能的分子机制。

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2026-01-06 DOI: 10.1016/j.plipres.2025.101373

Tomohiro Kimura, Richard M Epand

Diacylglycerol (DAG) and phosphatidic acid (PA), being positioned in the central hub of glycerophospholipid biosynthesis pathways, are lipids vital for the structural and functional integrity of the cell. DAG kinases (DGKs) are the enzymes responsible for the conversion of DAG to PA to regulate the dynamically changing spatiotemporal levels of these lipids in various organelles and cellular structures. DAG and PA thereby function intricately in mechanistic events like cell signaling in association with the intracellular lipid profiles controlling membrane physiology. In mammalian cells, there are ten DGK isoforms, i.e., α, β, γ, δ, η, κ, ε, ζ, ι, θ, and their splice variants. Recent advancement of structural prediction algorism enables us to gain unparalleled insights into their molecular architectures, despite limited experimental data available to date. The structural information gives fundamental clues to understand pertinent cellular events that are reviewed in this work on a broad range of topics in health and disease. Upon cell stimuli, DAG is formed by hydrolysis of a phospholipid such as phosphatidylinositol (PI) 4,5-bisphosphate (PI(4,5)P₂) via a phospholipase C (PLC). While relationship of the DGK activity with specific lipid acyl-chain species is being recognized, that with the sn-1 ether linkage like the vinyl ether has not yet been revealed. Importance of these relationships may be evident, considering the known regulation of the PLC activity by lipid rafts. Elucidation of molecular details of DGK functions in the context of membrane biophysics is thus essential for our understanding of cellular events in the individual tissues and organs.

二酰基甘油（DAG）和磷脂酸（PA）位于甘油磷脂生物合成途径的中心枢纽，是对细胞结构和功能完整性至关重要的脂质。DAG激酶（DGKs）是负责将DAG转化为PA的酶，以调节各种细胞器和细胞结构中这些脂质的时空动态变化水平。因此，DAG和PA在与控制膜生理的细胞内脂质谱相关的细胞信号传导等机制事件中发挥复杂的作用。在哺乳动物细胞中，DGK有10种同工型，即α、β、γ、δ、η、κ、ε、ι、ζ、θ及其剪接变体。结构预测算法的最新进展使我们能够获得对其分子结构的无与伦比的见解，尽管迄今为止可用的实验数据有限。结构信息为理解相关细胞事件提供了基本线索，这些事件在本工作中对健康和疾病的广泛主题进行了回顾。在细胞刺激下，DAG通过磷脂酶C （PLC）水解磷脂，如磷脂酰肌醇（PI） 4,5-二磷酸（PI(4,5)P2）。虽然DGK活性与特定脂质酰基链物种的关系已被确认，但与sn-1醚键（如乙烯基醚）的关系尚未被揭示。考虑到脂筏对PLC活性的已知调节，这些关系的重要性可能是显而易见的。因此，在膜生物物理学背景下阐明DGK功能的分子细节对于我们理解单个组织和器官中的细胞事件至关重要。

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引用次数: 0

Stearoyl-CoA desaturase in development and disease 硬脂酰辅酶a去饱和酶在发育和疾病中的作用。

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-12-29 DOI: 10.1016/j.plipres.2025.101374

Sampurna Ghosh , Roman Caceres , Sunny Congrove , James M. Ntambi , Biplab Dasgupta

The conversion of straight chain saturated fatty acids to their bent, unsaturated counterparts significantly increases their structural and functional complexity. Desaturation of fatty acids, where double bonds are introduced is an enzymatic reaction. Exploring 56 eukaryotic genomes, 275 desaturase homologs have been identified. Membrane-bound desaturases are the dominant form and are ubiquitous in bacteria and eukaryotes. Four subfamilies of desaturases introduce double bonds at distinct locations. Among them, the First Desaturase subfamily introduces the first double bond among which the stearoyl-CoA desaturases (SCDs) are the most predominant. SCD is a rate-limiting enzyme that generates monounsaturated fatty acids (MUFA) from saturated fatty acids (SFA) at the endoplasmic reticulum membrane, where SCD is localized. The MUFAs are utilized to produce a variety of cell membrane components including triglycerides, phospholipids, and cholesterol esters which play important roles in membrane fluidity, organelle function, and signal transduction. SCD activity is a critical regulator of SFA to MUFA ratio and, therefore, of overall cell function, growth, and survival. In this review, we will provide the latest updates on the expected as well as unanticipated roles of SCD in development, metabolism and disease with a focus on cancer and the central nervous system.

直链饱和脂肪酸转化为弯曲的不饱和脂肪酸显著增加了其结构和功能的复杂性。脂肪酸的去饱和，其中引入双键是一个酶促反应。在56个真核生物基因组中，鉴定出275个去饱和酶同源物。膜结合去饱和酶是主要形式，在细菌和真核生物中普遍存在。四个去饱和酶亚族在不同的位置引入双键。其中，第一个去饱和酶亚家族引入了第一个双键，其中硬脂酰辅酶a去饱和酶（SCDs）最为主要。SCD是一种限速酶，它从内质网膜上的饱和脂肪酸（SFA）生成单不饱和脂肪酸（MUFA），而内质网膜是SCD的所在地。mufa被用来产生各种细胞膜成分，包括甘油三酯、磷脂和胆固醇酯，它们在膜流动性、细胞器功能和信号转导中起重要作用。SCD活性是SFA与MUFA比率的关键调节因子，因此也是整体细胞功能、生长和存活的关键调节因子。在这篇综述中，我们将提供SCD在发育、代谢和疾病中的预期和未预料到的作用的最新进展，重点是癌症和中枢神经系统。

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引用次数: 0

The plant lipid contactome: emerging roles of inter-organelle contact sites in lipid metabolism 植物脂质接触组：细胞器间接触位点在脂质代谢中的新作用

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-12-26 DOI: 10.1016/j.plipres.2025.101372

Carolina Huercano , Miriam Moya-Barrientos , Oliver Cuevas , Carlos Cardenas , Joaquín J. Salas , Victoria Sanchez-Vera , Noemi Ruiz-Lopez

Membrane contact sites (MCSs) are fundamental hubs of inter-organelle communication that mediate the non-vesicular exchange of lipids, ions, and metabolites, thereby sustaining cellular homeostasis. In plants, the “contactome”—the dynamic network of all membrane contact sites—has evolved distinctive features to accommodate the requirements of a sessile, photosynthetic lifestyle and the presence of plastids. Within this network, the endoplasmic reticulum (ER) functions as a central hub for lipid biosynthesis and distribution, forming functionally important contacts with multiple organelles. Recent advances in high-resolution imaging, lipidomics, and molecular genetics are beginning to uncover the complexity of these inter-organelle connections and their contribution to lipid homeostasis in plants. This review summarizes current knowledge of the plant contactome, with a focus on lipid transfer proteins and lipid-modifying enzymes that maintain lipid balance during organelle biogenesis, plant development, and stress adaptation. Plant lipid transfer at membrane contact sites can be broadly divided into two mechanistic modes: precision-regulated “shuttles,” exemplified by the Ca²⁺-dependent SYT1-mediated diacylglycerol transfer at ER–plasma membrane interfaces, and high-capacity lipid transfer mechanisms, such those mediated by ATG2, that support rapid lipid flux during autophagosome biogenesis. Knowledge of lipid metabolism at plant membrane contact sites is still in its initial stages, and many of the underlying mechanisms remain unexplored. Major challenges include understanding how these sites integrate stress responses, metabolic fluxes, and organelle dynamics. Addressing these questions will be essential to unravel the unique aspects of plant lipid biology and may open opportunities for improving stress resilience and metabolic engineering in crops.

膜接触位点（MCSs）是细胞器间通讯的基本枢纽，介导脂质、离子和代谢物的非囊性交换，从而维持细胞内稳态。在植物中，“接触体”——所有膜接触点的动态网络——已经进化出独特的特征，以适应无根、光合作用的生活方式和质体的存在。在这个网络中，内质网（ER）作为脂质生物合成和分布的中心枢纽，与多个细胞器形成功能重要的联系。高分辨率成像、脂质组学和分子遗传学的最新进展开始揭示这些细胞器间连接的复杂性及其对植物脂质稳态的贡献。本文综述了植物接触体的最新研究进展，重点介绍了在细胞器生物发生、植物发育和逆境适应过程中维持脂质平衡的脂质转移蛋白和脂质修饰酶。植物在膜接触部位的脂质转移可以大致分为两种机制模式：精确调节的“穿梭体”，例如内质膜界面上依赖于Ca2+的syt1介导的二酰基甘油转移；以及高容量脂质转移机制，如由ATG2介导的，在自噬体生物发生过程中支持快速脂质通量。关于植物膜接触部位脂质代谢的知识仍处于初级阶段，许多潜在的机制仍未被探索。主要的挑战包括了解这些位点如何整合应激反应、代谢通量和细胞器动力学。解决这些问题对于揭示植物脂质生物学的独特方面至关重要，并可能为提高作物的应激恢复能力和代谢工程提供机会。

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引用次数: 0

Structure-guided dissection of the genetic variations within human LPA locus and its role in the development of cardiovascular diseases 人类LPA基因座遗传变异的结构导向解剖及其在心血管疾病发展中的作用

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-12-24 DOI: 10.1016/j.plipres.2025.101375

Ivan Antipenko , Anna Stepanova , Maxim Shkurnikov , Kianoush Jeiran , Ancha Baranova , Alexander Tonevitsky

Lipoprotein (a) [Lp(a)] is a highly heterogeneous lipoprotein particle promoting panvascular disease. Structurally, it consists of an LDL-like core covalently bound to apolipoprotein (a) [apo(a)]. Molecular determinants linking various genetic variants of apo(a) constituent of Lp(a) to vascular pathology remain incompletely defined.

We have built a model allowing dissection which variations in LPA gene are functional, and which are mere associates of these functional variations. Copy number changes in kringle IV type 2 (KIV-2), together with a spectrum of single nucleotide polymorphisms (SNPs), regulate apo(a) size, expression, and function. These variants can be broadly categorized into Lp(a)-increasing, Lp(a)-lowering, and null alleles, with distinct prevalence across populations. Notably, risk alleles such as rs10455872 and rs3798220 account for substantial variance in circulating Lp(a) and confer elevated susceptibility to coronary artery disease, whereas splice-altering and nonsense alleles markedly reduce Lp(a) concentrations.

The therapeutic implications of modifying circulating Lp(a) levels are profound. While conventional lipid-lowering therapies exert little influence on Lp(a), antisense oligonucleotides (pelacarsen) and small interfering RNA agents (olpasiran, SLN360) achieve robust Lp(a) reductions. Integrating genetic insights with structural modeling provides a framework to disentangle functional from proxy associations within LPA and neutralize the cardiovascular hazard conferred by elevated levels of Lp(a).

脂蛋白(a) [Lp(a)]是一种促进泛血管疾病的高度异质性脂蛋白颗粒。在结构上，它由一个与载脂蛋白(a)共价结合的ldl样核组成[apo(a)]。将Lp(a)的载脂蛋白(a)成分的各种遗传变异与血管病理联系起来的分子决定因素仍然不完全确定。我们已经建立了一个模型，允许解剖LPA基因的哪些变异是功能性的，哪些仅仅是这些功能变异的关联。kringle IV型2 （KIV-2）的拷贝数变化与单核苷酸多态性（SNPs）谱一起调节载脂蛋白(a)的大小、表达和功能。这些变异可大致分为Lp(a)增加、Lp(a)降低和无等位基因，在人群中具有不同的患病率。值得注意的是，rs10455872和rs3798220等风险等位基因在循环Lp(a)中有很大的差异，并赋予冠状动脉疾病的易感性增加，而剪接改变和无意义等位基因显著降低Lp(a)浓度。改变循环Lp(a)水平的治疗意义是深远的。虽然传统的降脂疗法对Lp(a)的影响很小，但反义寡核苷酸（pelacarsen）和小干扰RNA剂（olpasiran, SLN360）可以显著降低Lp(a)。将遗传见解与结构建模相结合，提供了一个框架，可以解开LPA内部的功能关联和代理关联，并消除Lp水平升高所带来的心血管危险(a)。

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引用次数: 0

From kinetoplastids to cancer: A magical myristate tour 从着丝质体到癌症：神奇的肉豆蔻之旅

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-12-03 DOI: 10.1016/j.plipres.2025.101362

Kyle Lethcoe, Robert O. Ryan

Myristic acid (14:0) is a relatively minor fatty acid in terms of abundance yet, in certain biological settings, it has a major impact. Although normally synthesized via the classical fatty acid biosynthesis pathway, in specific cases where larger quantities of myristate are required, animals express distinct thioesterase enzymes that hydrolyze the acyl-S-fatty acid synthase thioester bond prior to further chain elongation. In the parasitic kinetoplastid, Trypanosoma brucei, myristate is required for biosynthesis of dimyristoyl-glycosylphosphatidylinositol membrane anchors, to which variable surface glycoproteins are attached. This extracellular coat protein is changed periodically, allowing the parasite to evade host adaptive immunity. In protein N-myristoylation, this acyl chain is attached to N-terminal glycine residues via an amide bond. A search for inhibitors of N-myristoyltransferase (NMT) activity led to discovery of pyrazole sulfonamide compounds with potent T. brucei NMT inhibitory activity. While clinical development of these inhibitors for parasite-induced disease has not been realized, the observation that pyrazole sulfonamides possess anticancer activity led to drug development studies. Findings obtained with a specific pyrazole sulfonamide compound, branded as zelenirstat, have yielded promising results in cell culture studies, animal models and human clinical trials. This review describes research undertaken to validate zelenirstat as a cancer therapy option.

肉豆蔻酸（14:0）在丰度方面是一种相对次要的脂肪酸，但在某些生物环境中，它具有重大影响。虽然通常是通过经典的脂肪酸生物合成途径合成的，但在需要大量肉豆肉酸盐的特定情况下，动物表达不同的硫酯酶，在进一步的链延伸之前水解酰基- s脂肪酸合成酶硫酯键。在布氏锥虫的寄生动质体中，肉豆蔻酸是生物合成二肉豆蔻酰基糖基磷脂酰肌醇膜锚的必需物质，而可变的表面糖蛋白附着在二肉豆蔻酰肌醇膜锚上。这种细胞外外壳蛋白周期性地改变，使寄生虫能够逃避宿主的适应性免疫。在蛋白质n -肉豆蔻酰化中，这个酰基链通过酰胺键连接到n端甘氨酸残基上。在对n -肉豆浆酰基转移酶（NMT）活性抑制剂的研究中，发现了吡唑磺胺类化合物，这些化合物具有有效的布鲁氏T. NMT抑制活性。虽然这些寄生虫诱导疾病抑制剂的临床开发尚未实现，但吡唑磺胺类药物具有抗癌活性的观察导致了药物开发研究。一种特殊的吡唑磺胺化合物（zelenirstat）在细胞培养研究、动物模型和人体临床试验中取得了可喜的结果。本综述描述了验证zelenirstat作为癌症治疗选择的研究。

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引用次数: 0

Properties and biochemistry of phosphatidylcholine: diacylglycerol cholinephosphotransferase 磷脂酰胆碱的性质和生物化学：二酰基甘油胆碱磷酸酶

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-11-21 DOI: 10.1016/j.plipres.2025.101361

Brandon A. Ulch , Alyssa C. Clews , Caroline A. Reisiger , Li-Hua Zhu , Robert T. Mullen , Matthew S. Kimber , Yang Xu

Plant oils, primarily composed of triacylglycerols (TAGs), are essential for both food and industrial applications. TAGs consist of three fatty acids esterified to a glycerol backbone, and their value and functionality are largely determined by their fatty acid composition. Hence, enhancing the fatty acid profile of plant oils is a primary focus for improving their economic and practical potential. Phosphatidylcholine: Diacylglycerol Cholinephosphotransferase (PDCT), encoded by the REDUCED OLEATE DESATURATION1 (ROD1) gene in Arabidopsis thaliana, catalyzes the interconversion between phosphatidylcholine, the site of fatty acid modification, and diacylglycerol, the precursor of TAG assembly. PDCT plays a key role in determining the fatty acid composition and quality of oils, making it an attractive target for engineering crops with tailored oil profiles. This review systematically examines the biochemical, genetic, and molecular biology research on PDCT over the past decades, focusing on its phylogeny, physiological roles, regulation, biochemical characterization, structural features, and biotechnological applications. We also analyze the predicted structure of PDCT, which suggests a domain-swapped homodimer configuration based on AlphaFold3 modeling, and we discuss potential catalytic mechanisms. Finally, we highlight key open questions in the field and propose future research directions.

植物油主要由三酰甘油（TAGs）组成，在食品和工业应用中都是必不可少的。标签由三种脂肪酸酯化成甘油骨架，它们的价值和功能在很大程度上取决于它们的脂肪酸组成。因此，提高植物油的脂肪酸谱是提高其经济和实用潜力的主要焦点。磷脂酰胆碱：二酰基甘油胆碱磷酸转移酶（PDCT）是由拟南芥中OLEATE DESATURATION1 （ROD1）基因编码的，它催化磷脂酰胆碱（脂肪酸修饰位点）和二酰基甘油（TAG组装的前体）之间的相互转化。PDCT在确定油的脂肪酸组成和质量方面起着关键作用，使其成为具有定制油型的工程作物的有吸引力的目标。本文系统回顾了近几十年来关于PDCT的生物化学、遗传和分子生物学研究，重点介绍了其系统发育、生理作用、调控、生物化学表征、结构特征和生物技术应用。我们还分析了PDCT的预测结构，基于AlphaFold3模型的预测结构表明PDCT是一种结构交换的同二聚体构型，并讨论了潜在的催化机制。最后，提出了该领域有待解决的关键问题，并提出了未来的研究方向。

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引用次数: 0

N-Acylethanolamines in cancer: mechanisms and therapeutic potential of lipid regulators of tumor behavior 肿瘤中的n -酰基乙醇胺：肿瘤行为的脂质调节剂的机制和治疗潜力

IF 14.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research

Pub Date : 2025-11-01 DOI: 10.1016/j.plipres.2025.101358

M.F. Nanì , M.M. Rinaldi , M. Miraglia, R. Amico, P. De Cicco , B. Romano

N-Acylethanolamines (NAEs) are endogenous bioactive lipids generated from membrane glycerophospholipids, with key members including arachidonoylethanolamide (anandamide, AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA). These molecules engage multiple receptor systems such as cannabinoid (CB) receptors, peroxisome proliferator-activated receptors (PPARs), and transient receptor potential (TRP) channels to regulate inflammation, apoptosis, and metabolic signaling. Mounting evidence indicates that NAEs also exert multifaceted effects on tumor biology, influencing several hallmarks of cancer including proliferative signaling, angiogenesis, immune modulation, and resistance to cell death. Moreover, emerging congeners such as stearoylethanolamide (SEA) and linoleoylethanolamide (LEA) are gaining recognition for their roles in tumor-associated metabolic reprogramming and the control of inflammatory microenvironments. The enzymatic machinery that governs NAE synthesis (NAPE-PLD) and degradation (including FAAH and NAAA) represents a promising therapeutic axis for modulating NAE signaling in cancer. This review integrates current insights into the mechanistic functions of NAEs in oncogenesis, with a focus on their signaling networks, interaction with the tumor microenvironment, and the translational relevance of targeting NAE pathways in cancer therapy.

n -酰基乙醇胺（NAEs）是由膜甘油磷脂生成的内源性生物活性脂类，主要成员包括花生四烯酰乙醇酰胺（anandamide， AEA）、油基乙醇酰胺（OEA）和棕榈酰乙醇酰胺（PEA）。这些分子参与多种受体系统，如大麻素（CB）受体、过氧化物酶体增殖激活受体（PPARs）和瞬时受体电位（TRP）通道，以调节炎症、细胞凋亡和代谢信号。越来越多的证据表明，NAEs还对肿瘤生物学产生多方面的影响，影响肿瘤的几个特征，包括增殖信号、血管生成、免疫调节和对细胞死亡的抵抗。此外，新兴的同系物，如硬脂酰乙醇酰胺（SEA）和亚麻酰乙醇酰胺（LEA），因其在肿瘤相关代谢重编程和炎症微环境控制中的作用而获得认可。控制NAE合成（NAPE-PLD）和降解（包括FAAH和NAAA）的酶机制代表了在癌症中调节NAE信号传导的有希望的治疗轴。这篇综述整合了NAE在肿瘤发生中的机制功能，重点关注它们的信号网络、与肿瘤微环境的相互作用，以及靶向NAE通路在癌症治疗中的翻译相关性。

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