Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献_第2页

Gm15441 improves adipogenesis and insulin sensitivity by TXNIP regulation in white adipose tissue Gm15441通过TXNIP调节白色脂肪组织的脂肪形成和胰岛素敏感性。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2026-01-11 DOI: 10.1016/j.bbalip.2026.159718

Yinze Shi , Liying Huang , Xueyang Yang , Jiaoyue Zhang , Lulu Chen

Gm15441, a long non-coding RNA antisense to thioredoxin interacting protein (TXNIP) mRNA, exhibits undefined roles in adipogenesis and insulin resistance. This study aimed to explore its functions and mechanisms in white adipose tissue (WAT). Gm15441 expression was assessed in 3T3-L1 cells and WAT of insulin-resistant mice. Stable Gm15441 overexpression and knockdown 3T3-L1 cell models were established, followed by differentiation induction and analysis of lipid accumulation and differentiation markers. A subcutaneous adipose-specific Gm15441 overexpression mouse model was fed high-fat diets (HFD) and evaluated for metabolic parameters, adipogenesis, and insulin signaling. Subcellular localization in vitro was determined via fluorescence in situ hybridization, while transcriptome sequencing, TXNIP expression analysis, and RNA-RNA pull-down assays were performed. Results showed that Gm15441 expression increased during cell differentiation and decreased in insulin-resistant WAT. Gm15441 overexpression promoted adipogenesis in vitro, while knockdown suppressed it. In HFD-fed mice, adipose-specific Gm15441 overexpression enhanced adipogenesis, reduced blood glucose, and improved insulin sensitivity. Although PPARγ expression increased with cell differentiation, Gm15441 probes did not pull down PPARγ mRNA. Conversely, TXNIP protein levels decreased in Gm15441-overexpressing cells without corresponding changes in mRNA levels, but Gm15441 probes successfully pulled down TXNIP mRNA. These results suggested that Gm15441 may promote adipogenesis and enhance insulin sensitivity by inhibiting TXNIP expression.

Gm15441是硫氧还蛋白相互作用蛋白（TXNIP） mRNA的长链非编码RNA反义，在脂肪形成和胰岛素抵抗中发挥的作用尚不明确。本研究旨在探讨其在白色脂肪组织（WAT）中的作用及其机制。评估Gm15441在胰岛素抵抗小鼠3T3-L1细胞和WAT中的表达。建立稳定的Gm15441过表达和敲低3T3-L1细胞模型，诱导分化，分析脂质积累和分化标志物。皮下脂肪特异性Gm15441过表达小鼠模型被喂食高脂饲料（HFD），并评估代谢参数、脂肪生成和胰岛素信号。通过荧光原位杂交确定体外亚细胞定位，同时进行转录组测序、TXNIP表达分析和RNA-RNA拉下测定。结果显示，Gm15441在胰岛素抵抗型WAT细胞分化过程中表达增加，而在胰岛素抵抗型WAT中表达减少。Gm15441过表达促进体外脂肪形成，而敲低抑制。在饲喂hfd的小鼠中，脂肪特异性Gm15441过表达增强了脂肪生成，降低了血糖，并改善了胰岛素敏感性。虽然PPARγ的表达随着细胞分化而增加，但Gm15441探针不降低PPARγ mRNA的表达。相反，在Gm15441过表达的细胞中，TXNIP蛋白水平下降，但mRNA水平没有相应的变化，但Gm15441探针成功地拉低了TXNIP mRNA。提示Gm15441可能通过抑制TXNIP的表达促进脂肪形成，提高胰岛素敏感性。

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引用次数: 0

Yeast phosphatidylinositol transfer protein Pdr16 supports azole resistance independently of lipid droplets 酵母磷脂酰肌醇转移蛋白Pdr16支持独立于脂滴的唑抗性。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2026-01-11 DOI: 10.1016/j.bbalip.2026.159721

Lucia Pokorná, Dana Tahotná, Rebeka Rusnáková, Zuzana Pevalová, Dominik Šťastný, Peter Griač

•
Pdr16p is a potential target for preventing the development of azole resistance in fungi.
•
The molecular mechanism by which Pdr16p supports azole resistance remains unclear.
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Pdr16p predominantly localizes to lipid droplets (LDs) in yeast cells.
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Neither the presence of LDs nor the localization of Pdr16p to LDs contributes to azole resistance in yeast.
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Pdr16p may play a role in adjusting ergosterol biosynthesis in response to azole treatment.

•Pdr16p是防止真菌产生唑抗性的潜在靶标。•Pdr16p支持抗唑的分子机制尚不清楚。•Pdr16p主要定位于酵母细胞的脂滴（ld）。•无论是ld的存在还是Pdr16p对ld的定位都无助于酵母对唑的抗性。•Pdr16p可能在调节麦角甾醇生物合成中发挥作用，以响应唑治疗。

引用次数: 0

The endocannabinoid-derived prostaglandin glycerol esters and prostaglandin ethanolamides modulate intestinal epithelial hallmarks of colitis 内源性大麻素衍生的前列腺素甘油酯和前列腺素乙醇酰胺调节结肠炎的肠上皮特征。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2026-01-10 DOI: 10.1016/j.bbalip.2026.159719

Joan Bestard-Escalas , Olivia Sasportes , Hafsa Ameraoui , Mar González-Nicolau , Mireille Alhouayek , Giulio G. Muccioli

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract with a high impact on patients' quality of life.

The endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA) are important modulators of inflammation. Their metabolism by cyclooxygenase (COX)-2 produces prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs) that are endogenous analogues of the arachidonic acid-derived prostaglandins. Several PG-G and PG-EA possess interesting biological properties, notably in the context of colitis as we reported for PGD₂-G. However, while the properties of prostaglandins (such as PGE₂) on epithelial cells in the context of colon inflammation are well described, the biological effects of PG-Gs and PG-EAs are unknown.

Here we used Caco-2 spheroids and mouse colon organoids to evaluate how PG-Gs and PG-EAs modulate three epithelial hallmarks of colitis, namely the epithelial barrier integrity, the production of cytokines, and the wound healing process. Importantly, we tested the corresponding prostaglandins in parallel.

When analyzing the effects of these prostanoids on the production of pro-inflammatory cytokines, we found that PGD₂-G did decrease the production of TNFα and MCP-1 in activated Caco-2 spheroids. On colon organoids, PGE₂-G modulated the levels of TNFα, MIP2α, and KC and improved the survival of colon organoids in a DSS-plating efficiency assay without affecting stem cell dynamics. Our results put forth differential effects for PG-Gs, PG-EAs and the corresponding prostaglandins, and suggest that PGE₂-G could be an interesting lipid mediator in the context of colon epithelium inflammation.

炎症性肠病（IBD）是一种严重影响患者生活质量的胃肠道慢性炎症性疾病。内源性大麻素2-花生四烯醇甘油（2-AG）和n -花生四烯醇乙醇胺（AEA）是重要的炎症调节剂。它们通过环氧化酶(COX)-2代谢产生前列腺素甘油酯（PG-G）和前列腺素乙醇酰胺（PG-EA），它们是花生四烯酸衍生的前列腺素的内源性类似物。一些PG-G和PG-EA具有有趣的生物学特性，特别是在结肠炎的背景下，正如我们报道的PGD2-G。然而，虽然前列腺素（如PGE2）在结肠炎症背景下对上皮细胞的特性已经得到了很好的描述，但PG-G和PG-EA的生物学效应尚不清楚。在这里，我们使用Caco-2球体和小鼠结肠类器官来评估PG-G和PG-EA如何调节结肠炎的三个上皮标志，即上皮屏障完整性、细胞因子的产生和伤口愈合过程。重要的是，我们平行测试了相应的前列腺素。在分析这些前列腺素对促炎细胞因子产生的影响时，我们发现PGD2-G确实降低了活化Caco-2球体中TNFα和MCP-1的产生。在结肠类器官上，PGE2-G调节了TNFα、MIP2α和KC的水平，并在不影响干细胞动力学的情况下提高了结肠类器官的存活率。我们的研究结果表明PG-Gs、pg - ea和相应的前列腺素的不同作用，并提示PGE2-G在结肠上皮炎症中是一种有趣的脂质介质。

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引用次数: 0

Valproate causes inositol depletion in yeast by decreasing levels of phosphatidic acid and increasing Opi1-mediated repression of INO1 expression 丙戊酸通过降低磷脂酸水平和增加opi1介导的INO1表达抑制，导致酵母肌醇耗竭

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2026-01-08 DOI: 10.1016/j.bbalip.2026.159717

Chisom J. Onu , Michael Adu , Gil-Soo Han , George M. Carman , Miriam L. Greenberg

Valproic acid (VPA) is a widely prescribed mood stabilizer used in the pharmacological management of bipolar disorder (BD), a psychiatric illness that affects 2% of the world's population. Although VPA has been in use for four decades, the therapeutic mechanism of action has not been determined. Inositol depletion is a proposed mechanism, but how VPA depletes inositol is not understood. Using the yeast model, in which the inositol biosynthetic pathway has been well characterized, we show that VPA supplementation leads to decreased levels of phosphatidic acid (PA), including decreased PA species 34:1. Supplementation with PA 34:1 or increasing PA levels by deletion of PAH1 partially rescued VPA-induced repression of INO1. VPA-mediated repression is mediated by the Opi1-Ino2 interaction, as INO1 expression is not repressed in an Ino2 mutant that does not bind to Opi1. The central role of PA in VPA-mediated repression has implications for the mechanism of action of VPA in mammalian cells.

丙戊酸（VPA）是一种广泛使用的情绪稳定剂，用于双相情感障碍（BD）的药理治疗，双相情感障碍是一种影响全球2%人口的精神疾病。虽然VPA已经使用了40年，但其治疗机制尚未确定。肌醇消耗是一种被提出的机制，但VPA如何消耗肌醇尚不清楚。利用酵母模型，其中肌醇的生物合成途径已经被很好地表征，我们发现补充VPA导致磷脂酸（PA）水平降低，包括PA种类减少34:1。补充pa34:1或通过删除PAH1来增加PA水平部分地恢复vpa诱导的INO1抑制。vpa介导的抑制是由Opi1-Ino2相互作用介导的，因为INO1的表达在不与Opi1结合的Ino2突变体中不受抑制。在VPA介导的抑制中，PA的中心作用暗示了VPA在哺乳动物细胞中的作用机制。

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引用次数: 0

Neuroprotective effect of berberine-loaded niosomes against brain injury in dyslipidemic rats: The interplay between oxidative stress, mitochondrial dysfunction and apoptotic signals 载小檗碱的神经小体对血脂异常大鼠脑损伤的神经保护作用：氧化应激、线粒体功能障碍和凋亡信号之间的相互作用。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2026-01-06 DOI: 10.1016/j.bbalip.2026.159716

Mohamed Fouad Mansour , Amany Behairy , Tarek khamis , Haiam A. Mohammed , Amira Ebrahim Alsemeh , Asmaa Monir Eltaweel , Mahran Mohamed Abd El-Emam

Dyslipidemia is a major risk factor for the development of atherosclerosis, cardiovascular diseases, and brain injury. Berberine (BER), a type of isoquinoline alkaloid, has the potential to enhance mitochondrial performance owing to its remarkable antioxidant properties. This study aimed to explore how berberine-loaded niosomes (BER-NIO) would alleviate the adverse effects of brain injury in dyslipidemic rats. Hence, for this purpose, the genes of electron transport chain, mitochondrial dynamics, mitophagy, and apoptosis were assessed in brain tissue. Moreover, molecular docking analysis was done to predict this target pathway.

Methods

Thirty-five male Sprague Dawley rats were separated into five groups: (I) Control (Ctl), (II) Poloxamer 407 (Plx), (III) Plx + BER-NIO, (IV) Plx + NC, and (V) Plx + BER-NIO + NC.

Results

BER-NIO improved lipid profile, brain MDA, and brain total antioxidant capacity (TAC) compared to Plx group. Moreover, BER-NIO was able to notably restore the activity of mitochondrial respiratory chain complexes through upregulation of the mRNA expression levels of Ndufs1, Sdhc, Coq8a, Cox6a2 and Atp5f1a. It also enhanced the mitochondrial dynamics via modulation of the transcriptional level of DRP-1, MFN-1, and MFN-2. In addition, administration of BER-NIO to dyslipidemic rats regulated the mitophagy pathway through alteration of PINK-1/Prkn pathway within brain tissue. Furthermore, BER-NIO notably enhanced neurological function through reduction of brain pathological alterations, suppression of apoptosis and decrease of the biomarker for brain injury (GFAP). Interestingly, molecular docking analysis revealed a strong binding affinity between BER and MFN-2, PINK-1 and caspase-3.

Conclusion

The findings suggested that the BER-NIO is effective in the reduction of brain injury in dyslipidemic rats via modulation of brain oxidant/antioxidant status and mitochondrial functions.

血脂异常是动脉粥样硬化、心血管疾病和脑损伤的主要危险因素。小檗碱（Berberine， BER）是一类异喹啉类生物碱，由于其显著的抗氧化特性，具有提高线粒体性能的潜力。本研究旨在探讨载小檗碱niosomes （BER-NIO）如何减轻血脂异常大鼠脑损伤的不良反应。因此，为此，我们在脑组织中评估了电子传递链、线粒体动力学、线粒体自噬和细胞凋亡的基因。并通过分子对接分析对该靶点通路进行了预测。方法：35只雄性Sprague Dawley大鼠分为5组：(I)对照（Ctl），（II） Poloxamer 407 (Plx), (III) Plx + BER-NIO, (IV) Plx + NC, (V) Plx + BER-NIO + NC。结果：与Plx组相比，BER-NIO改善了脂质谱、脑MDA和脑总抗氧化能力（TAC）。此外，BER-NIO能够通过上调Ndufs1、Sdhc、Coq8a、Cox6a2和Atp5f1a的mRNA表达水平，显著恢复线粒体呼吸链复合物的活性。它还通过调节DRP-1、MFN-1和MFN-2的转录水平来增强线粒体动力学。此外，对血脂异常大鼠给予BER-NIO可通过改变脑组织内的PINK-1/Prkn途径调节线粒体自噬途径。此外，BER-NIO通过减少脑病理改变、抑制细胞凋亡和降低脑损伤生物标志物（GFAP）显著增强神经功能。有趣的是，分子对接分析显示，BER与MFN-2、PINK-1和caspase-3之间具有很强的结合亲和力。结论：BER-NIO可能通过调节脑氧化/抗氧化状态和线粒体功能来减轻血脂异常大鼠的脑损伤。

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引用次数: 0

MiR-432 mediates bidirectional regulation in the determination of adipocyte fate MiR-432介导脂肪细胞命运的双向调节。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2026-01-05 DOI: 10.1016/j.bbalip.2026.159715

Liming Tian , Guan Wang , Shuhong Zhang , Zhaohua He , Fangfang Zhao , Menghan Chang , Wei Han , Dandan Ye , Shaobin Li , Guangli Yang

Fat deposition represents a fundamental physiological process in mammalian energy metabolism, yet its molecular regulatory mechanisms remain incompletely understood. Adipocytes, the primary site of fat storage, develop through proliferation and differentiation of preadipocytes—a process controlled by multiple molecular regulators. MicroRNAs (miRNAs) act as crucial post-transcriptional regulators and play an essential role in mammalian adipogenesis. However, their specific functions in ovine tail fat deposition remain poorly characterized. This study aimed to systematically investigate the regulatory role of miR-432 in adipogenesis using sheep tail fat as a model system. Through establishing an in vitro preadipocyte culture model and implementing gain- and loss-of-function approaches via miRNA overexpression and antisense oligonucleotide inhibition, we demonstrated that elevated expression of miR-432 significantly enhanced preadipocyte proliferation, accompanied by upregulation of proliferation-related genes (Cyclin D, PCNA). However, it decreased lipid droplet accumulation and reduced the expression of differentiation markers (PPARγ, FABP4). Conversely, inhibition of miR-432 reduced cellular proliferation, downregulated key cell cycle genes (CCNB1, Cyclin B3), and enhanced adipogenic differentiation, as evidenced by increased lipid droplet formation and elevated expression of adipogenic genes (PPARγ, Adiponectin, FABP4). These findings demonstrate that miR-432 exerts a dual regulatory role in sheep tail adipogenesis by modulating both proliferative and differentiative processes in adipocytes. This research provides novel molecular insights into the regulatory mechanisms underlying fat deposition.

脂肪沉积是哺乳动物能量代谢的一个基本生理过程，但其分子调控机制尚不完全清楚。脂肪细胞是脂肪储存的主要部位，通过前脂肪细胞的增殖和分化形成，这一过程受多种分子调控。MicroRNAs （miRNAs）是重要的转录后调控因子，在哺乳动物脂肪形成中发挥重要作用。然而，它们在绵羊尾部脂肪沉积中的具体功能仍不清楚。本研究旨在以羊尾脂肪为模型系统探讨miR-432在脂肪形成中的调控作用。通过建立体外前脂肪细胞培养模型，并通过miRNA过表达和反义寡核苷酸抑制实现功能增益和功能丧失方法，我们证明miR-432的表达升高可显著增强前脂肪细胞的增殖，并伴有增殖相关基因（Cyclin D， PCNA）的上调。然而，它可以减少脂滴积累，降低分化标志物（PPARγ, FABP4）的表达。相反，抑制miR-432会降低细胞增殖，下调关键细胞周期基因（CCNB1, Cyclin B3），并增强成脂分化，这可以通过脂滴形成增加和成脂基因（PPARγ，脂联素，FABP4）表达升高来证明。这些发现表明，miR-432通过调节脂肪细胞的增殖和分化过程，在羊尾脂肪形成中发挥双重调节作用。这项研究为脂肪沉积的调控机制提供了新的分子视角。

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引用次数: 0

A retrospective on phosphatidylinositol transfer proteins (PITPs) – A fifty-year journey 磷脂酰肌醇转移蛋白（PITPs）的回顾——50年的历程。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2025-12-18 DOI: 10.1016/j.bbalip.2025.159714

Shamshad Cockcroft

This retrospective traces the evolution of our understanding of the phosphatidylinositol transfer protein (PITP) family over the past fifty years, beginning with its purification. I summarise the early identification of PITPs as phosphatidylinositol/phosphatidylcholine (PI/PC) transfer proteins and describe how the conserved PITP domain was subsequently recognised in five mammalian proteins, occurring either as a single domain or within a multi-domain architecture. Parallel genetic studies in Drosophila led to the discovery of RdgB, a retinal degeneration mutant protein containing a PITP domain. Later work revealed that some members of the PITP family members mediate PI/PA (phosphatidate) exchange enabling the reciprocal transfer of PA and PI during phospholipase C (PLC) signalling. PITPs thus function as key lipid exchangers, delivering PI for synthesis of phosphorylated derivatives including phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P₂) across cellular compartments. These activities position PITPs at the core of fundamental processes such as PLC signalling and Golgi membrane trafficking, where phosphoinositides play central regulatory roles. Finally, I highlight how PITPs have emerged as critical factors in diverse physiological processes and as contributors to a growing range of pathological conditions.

本回顾回顾了过去50年来我们对磷脂酰肌醇转移蛋白（PITP）家族的理解的演变，从其纯化开始。我总结了PITP作为磷脂酰肌醇/磷脂酰胆碱（PI/PC）转移蛋白的早期鉴定，并描述了保守的PITP结构域随后如何在五种哺乳动物蛋白中被识别，这些蛋白要么作为单一结构域出现，要么在多结构域结构中出现。对果蝇的平行遗传研究导致了RdgB的发现，RdgB是一种含有PITP结构域的视网膜变性突变蛋白。后来的研究表明，一些PITP家族成员介导PI/PA（磷脂酸）交换，使PA和PI在磷脂酶C （PLC）信号传导过程中相互转移。因此，pitp作为关键的脂质交换器，传递PI用于合成磷酸化衍生物，包括磷脂酰肌醇4-磷酸（PI4P）和磷脂酰肌醇(4,5)-二磷酸（PI(4,5)P2）。这些活动使pitp处于PLC信号传导和高尔基膜运输等基本过程的核心，其中磷酸肌苷起着核心调节作用。最后，我强调了pitp如何在各种生理过程中作为关键因素出现，并作为越来越多的病理条件的贡献者。

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引用次数: 0

ACADVL upregulation is associated with placental ferroptosis in intrahepatic cholestasis of pregnancy ACADVL上调与妊娠肝内胆汁淤积症患者胎盘铁下垂有关。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2025-12-13 DOI: 10.1016/j.bbalip.2025.159711

Mi Tang , Jianghui Cai , Ling Zhang , Liling xiong , Xuejia Gong , Jinzhu Fu , Peilin Wang , Mengqiu Luo , Hong Liu , Ying Ye , Min Yu , Heng Yu , ShaSha Xing , Xiao Yang

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a disorder characterized by maternal pruritus and elevated total bile acid concentrations during pregnancy, posing severe fetal risks associated with placental dysfunction. However, the mechanisms underlying ICP remain to be fully elucidated.

Methods

An integrated approach was employed, utilizing placental scRNA-seq, LC-MS/MS-based lipidomics, and public RNA-seq data. The AUCell package, PPI network analysis, Random Forest, Support Vector Machine, and LASSO regression analyses were utilized to explore mitochondrial functions and identify hub mitochondria-related genes (MRGs). KEGG, GSEA, and GSVA were employed to investigate potential biological mechanisms. Key findings were validated by immunohistochemistry, immunofluorescence, and western blotting. Reactive oxygen species (ROS), malondialdehyde (MDA) and transmission electron microscopy were utilized to evaluate oxidative stress levels, lipid peroxidation and conduct ultrastructural examinations of mitochondria, respectively.

Results

MRGs are primarily distributed in villous cytotrophoblast (VCT). KEGG analysis of VCT indicated a close association with oxidative phosphorylation, ROS, Lipid. ACADVL was identified as a hub MRG and was found increased in ICP placenta, particularly in VCT. Functional analysis of ACADVL^high VCT revealed enrichment in fatty acid metabolism and oxidative phosphorylation. Lipidomics identified substantial alterations in glycerophospholipid and glycerolipid metabolism, and polyunsaturated fatty acid (PUFA) metabolism pathways. Experimentally, we observed the mitochondrial ACADVL localization, increased DRP1, decreased MFN2 and GPX4, and increased ROS and MDA levels in ICP. Electron microscopy revealed ultrastructural features consistent with ferroptosis.

Conclusion

This study proposes a novel model linking ACADVL, lipid metabolism, mitochondrial dysfunction, and ferroptosis in ICP pathogenesis.

妊娠肝内胆汁淤积症（ICP）是一种以妊娠期间母体瘙痒和总胆汁酸浓度升高为特征的疾病，与胎盘功能障碍相关，对胎儿造成严重风险。然而，ICP的机制仍有待充分阐明。方法：采用综合方法，利用胎盘scRNA-seq、LC-MS/MS-based脂质组学和公开的RNA-seq数据。利用AUCell软件包、PPI网络分析、随机森林、支持向量机和LASSO回归分析来探索线粒体功能并鉴定中心线粒体相关基因（mrg）。使用KEGG、GSEA和GSVA来研究潜在的生物学机制。主要发现通过免疫组织化学、免疫荧光和免疫印迹进行验证。采用活性氧（ROS）、丙二醛（MDA）和透射电镜分别评价氧化应激水平、脂质过氧化和线粒体超微结构检查。结果：核磁共振成像主要分布于绒毛细胞滋养层（VCT）。KEGG分析显示VCT与氧化磷酸化、ROS、脂质密切相关。ACADVL被确定为枢纽MRG，并在ICP胎盘中发现增加，特别是在VCT中。ACADVLhigh VCT的功能分析显示脂肪酸代谢和氧化磷酸化富集。脂质组学鉴定了甘油磷脂和甘油脂代谢以及多不饱和脂肪酸（PUFA）代谢途径的实质性改变。实验中，我们观察到ICP线粒体ACADVL定位，DRP1升高，MFN2和GPX4降低，ROS和MDA水平升高。电镜显示超微结构特征与铁下垂一致。结论：本研究提出了一种将ACADVL、脂质代谢、线粒体功能障碍和铁下垂与ICP发病机制联系起来的新模型。

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引用次数: 0

1H NMR studies of alterations in lipoprotein profiles in women diagnosed with gestational diabetes mellitus (GDM) and after delivery 诊断为妊娠期糖尿病（GDM）的妇女和分娩后脂蛋白谱变化的1H NMR研究。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2025-12-12 DOI: 10.1016/j.bbalip.2025.159713

Izabela Burzynska-Pedziwiatr , Malgorzata Bukowiecka-Matusiak , Barbara Pacholczyk-Sienicka , Katarzyna Cypryk , Monika Zurawska-Klis , Andrzej Zieleniak , Lukasz Albrecht , Lucyna A. Wozniak

The lipid abnormalities are observed in pregnant women with normal glucose tolerance (NGT) and those diagnosed with gestational diabetes mellitus (GDM), but in the latter, they are intensified and may indicate underlying metabolic dysfunction that transiently manifests during pregnancy. Due to the complex relationship between lipid metabolism and glucose regulation, alterations in lipoproteins may act as preliminary biomarkers for the early detection and monitoring of GDM and postpartum changes.

In the current study, we performed a ¹H NMR analysis of plasma lipoproteins in the cohort comprising pregnant NGT women and those diagnosed with GDM at three critical time points: 24–28 gestation week and 3 and 12 months postpartum.

After assignment of lipoprotein-associated signals in NMR spectra, Partial Least Squares Discriminant Analysis (PLS-DA) revealed clear distinctions between NGT and GDM groups.

Correlation analysis revealed a moderate negative correlation of CH₃VLDL, a moderate positive correlations of CH₂CH₂C=C with 2 h-OGTT and 1 h-OGTT, and a significant negative correlation of CH₃VLDL, and a positive correlation of CH₂CH₂C=C were noted for HOMA IR.

At the 3-months mark, the concentrations of (CH₂)_n LDL, CH₂CH₂CH₂CO VLDL, all unsaturated lipids, and (CH=CH) LDL + VLDL, CH₂/CH₃ LDL + VLDL, and CH=CH/CH₃ LDL + VLDL were decreased, while the concentrations of (C18 VLDL, CH₃ LDL, CH₂CH₂C=C, CH₂C=C, CH₂CO, C=CCH₂C=C, choline N(CH₃)₃, glyceryl CH₂OCOR) were increased. The concentrations of selected fractions at the 1-year postpartum time point remained unchanged.

Our findings provide essential insights into lipoprotein dysregulation in GDM and underscore possible implications for early intervention and long-term metabolic risk reduction for maternal health.

脂质异常见于糖耐量正常（NGT）和妊娠期糖尿病（GDM）的孕妇，但在后者中，脂质异常加剧，可能表明妊娠期间短暂表现出潜在的代谢功能障碍。由于脂质代谢和葡萄糖调节之间的复杂关系，脂蛋白的改变可能作为早期发现和监测GDM和产后变化的初步生物标志物。在本研究中，我们对NGT孕妇和GDM患者在三个关键时间点（妊娠24-28周，产后3个月和12个 月）的血浆脂蛋白进行了1H NMR分析。在NMR谱中分配脂蛋白相关信号后，偏最小二乘判别分析（PLS-DA）揭示了NGT和GDM组之间的明显差异。相关性分析显示，CH3VLDL与HOMA IR呈中度负相关，CH2CH2C=C与2 h-OGTT和1 h-OGTT呈中度正相关，CH3VLDL与HOMA IR呈显著负相关，CH2CH2C=C与HOMA IR呈正相关。3个月时，（CH2）n LDL、CH2CH2CH2CO VLDL、各种不饱和脂质、（CH=CH） LDL + VLDL、CH2/CH3 LDL + VLDL、CH=CH/CH3 LDL + VLDL浓度降低，而（C18 VLDL、CH3 LDL、CH2CH2C=C、CH2C=C、CH2CO、C=CCH2C=C、胆碱n (CH3)3、甘油CH2OCOR）浓度升高。在产后1年的时间点，所选组分的浓度保持不变。我们的研究结果为GDM的脂蛋白失调提供了重要的见解，并强调了早期干预和长期降低孕产妇健康代谢风险的可能意义。

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引用次数: 0

Curcumol ameliorates high-fat diet-induced hepatic fibrosis via dual regulation of FXR-CREB and Rab18-mediated hepatic stellate cell lipophagy 姜黄酚通过双重调节FXR-CREB和rab18介导的肝星状细胞脂质吞噬来改善高脂肪饮食诱导的肝纤维化。

IF 3.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids

Pub Date : 2025-12-11 DOI: 10.1016/j.bbalip.2025.159710

Na Wei , Wanyu Feng , Meijun Pan , Xinyi Xu , Shuguo Zheng , Huanhuan Jin

Curcumol, a bioactive constituent derived from Rhizoma Curcumae roots, possesses anti-inflammatory and anti-viral properties. This study investigated its therapeutic effects on lipophagy in hepatic stellate cells (HSCs) and lipid accumulation in hepatocytes within a model of high-fat diet-induced hepatic fibrosis, along with the underlying molecular mechanisms. Initially, curcumol treatment significantly attenuated lipid droplets (LDs) degradation and suppressed HSC activation, effects potentially associated with the inhibition of lipophagy. These outcomes were partially reversed by Rab18 overexpression, which modulates the autophagy-lysosomal pathway. Moreover, the ameliorative effect of curcumol on choline-deficient, L-amino acid-defined, 45 % high-fat diet (CDAHFD)-induced hepatic pathology was partially abolished upon Rab18 overexpression in mice. Importantly, curcumol promoted Farnesoid X receptor (FXR) expression, which inhibited the CREB/TORC2 interaction, thereby further suppressing LC3B expression and activation in LX2 cells. Additionally, curcumol impeded LD expansion and reduced lipid accumulation in palmitic acid (PA)-treated BNL-CL.2 cells and hepatocytes from CDAHFD-fed mice by inhibiting LD–endoplasmic reticulum (ER) contact formation, which could be reversed by Rab18 overexpression. In conclusion, curcumol inhibits HSC lipophagy by downregulating Rab18-mediated LD–autophagosome formation and enhancing the FXR–CREB interaction. Furthermore, it ameliorates hepatocyte lipid accumulation in fibrotic livers by disrupting Rab18-dependent LD–ER contacts. These findings underscore the therapeutic potential of curcumol in the treatment of HFD-induced hepatic fibrosis.

姜黄酚是一种从姜黄根中提取的生物活性成分，具有抗炎和抗病毒的特性。本研究在高脂肪饮食诱导的肝纤维化模型中研究了其对肝星状细胞（HSCs）脂质吞噬和肝细胞脂质积累的治疗作用，以及潜在的分子机制。最初，姜黄酚治疗可显著减弱脂滴（ld）降解并抑制HSC活化，其作用可能与抑制脂噬有关。这些结果被Rab18过表达部分逆转，Rab18过表达调节自噬-溶酶体途径。此外，姜黄酚对胆碱缺乏，l -氨基酸定义，45% %高脂肪饮食（CDAHFD）诱导的肝脏病理的改善作用在Rab18过表达小鼠中部分被消除。重要的是，姜黄酚促进Farnesoid X受体（FXR）表达，抑制CREB/TORC2相互作用，从而进一步抑制LX2细胞中LC3B的表达和激活。此外，姜黄酚抑制了棕榈酸（PA）处理的BNL-CL的LD扩张并减少了脂质积累。通过抑制ld -内质网（ER）接触形成，可通过Rab18过表达逆转。综上所述，姜黄酚通过下调rab18介导的ld -自噬体形成和增强FXR-CREB相互作用来抑制HSC脂噬。此外，它通过破坏rab18依赖的LD-ER接触来改善纤维化肝脏中的肝细胞脂质积累。这些发现强调了姜黄酚在治疗hfd诱导的肝纤维化中的治疗潜力。

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