Journal of Lipid Research最新文献_第8页

Participation of lipids in the tumor response to photodynamic therapy and its exploitation for therapeutic gain. 脂质参与肿瘤对光动力治疗的反应及其对治疗效果的利用。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-14 DOI: 10.1016/j.jlr.2024.100729

Mladen Korbelik, Michal Heger, Albert W Girotti

{"title":"Participation of lipids in the tumor response to photodynamic therapy and its exploitation for therapeutic gain.","authors":"Mladen Korbelik, Michal Heger, Albert W Girotti","doi":"10.1016/j.jlr.2024.100729","DOIUrl":"10.1016/j.jlr.2024.100729","url":null,"abstract":"Hydroperoxides of unsaturated membrane lipids (LOOHs) are the most abundant non-radical intermediates generated by photodynamic therapy (PDT) of soft tissues such as tumors and have far longer average lifetimes than singlet oxygen or oxygen radicals formed during initial photodynamic action. LOOH-initiated post-irradiation damage to remaining membrane lipids (chain peroxidation) or to membrane-associated proteins remains largely unrecognized. Such after-light processes could occur during clinical oncological PDT, but this is not well-perceived by practitioners of this therapy. In general, the pivotal influence of lipids in tumor responses to PDT needs to be better appreciated. Of related importance is the fact that most malignant tumors have dramatically different lipid metabolism compared with healthy tissues, and this too is often ignored. The response of tumors to PDT appears especially vulnerable to manipulations within the tumor lipid microenvironment. This can be exploited for therapeutic gain with PDT, as exemplified here by the combined treatment with the antitumor lipid edelfosine.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100729"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828923","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

Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1. 在GPIHBP1中，脂蛋白脂肪酶从硫酸肝素中竞争性置换是由一个无序的酸性簇组织的。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2025-01-13 DOI: 10.1016/j.jlr.2025.100745

Anamika Biswas, Samina Arshid, Kristian Kølby Kristensen, Thomas J D Jørgensen, Michael Ploug

{"title":"Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.","authors":"Anamika Biswas, Samina Arshid, Kristian Kølby Kristensen, Thomas J D Jørgensen, Michael Ploug","doi":"10.1016/j.jlr.2025.100745","DOIUrl":"10.1016/j.jlr.2025.100745","url":null,"abstract":"Movement of lipoprotein lipase (LPL) from myocytes or adipocytes to the capillary lumen is essential for intravascular lipolysis and plasma triglyceride homeostasis-low LPL activity in the capillary lumen causes hypertriglyceridemia. The trans-endothelial transport of LPL depends on ionic interactions with GPIHBP1's intrinsically disordered N-terminal tail, which harbors two acidic clusters at positions 5-12 and 19-30. This polyanionic tail provides a molecular switch that controls LPL detachment from heparan sulfate proteoglycans (HSPGs) by competitive displacement. When the acidic tail was neutralized in gene-edited mice, LPL remained trapped in the sub-endothelial spaces triggering hypertriglyceridemia. Due to its disordered state, the crystal structure of LPL•GPIHBP1 provided no information on these electrostatic interactions between LPL and GPIHBP1 acidic tail. In the current study, we positioned the acidic tail on LPL using zero-length crosslinking. Acidic residues at positions 19-30 in GPIHBP1 mapped to Lys445, Lys441, Lys414, and Lys407 close to the interface between the C- and N-terminal domains in LPL. Modeling this interface revealed widespread polyelectrolyte interactions spanning both LPL domains, which explains why the acidic tail stabilizes LPL activity and protein conformation. In functional assays, we showed that the acidic cluster at 19-30 also had the greatest impact on preserving LPL activity, mitigating ANGPTL4-catalyzed LPL inactivation, preventing PSCK3-mediated LPL cleavage, and, importantly, displacing LPL from HSPGs. Our current study provides key insights into the biophysical mechanism(s) orchestrating intravascular compartmentalization of LPL activity-an intriguing pathway entailing competitive displacement of HSPG-bound LPL by a disordered acidic tail in GPIHBP1.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100745"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006791","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

Staying sane in the membrane: Neutral sphingomyelinase 2 as a master regulator of plasma membrane ceramide. 在膜内保持清醒：中性鞘磷脂酶2作为质膜神经酰胺的主要调节因子。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-26 DOI: 10.1016/j.jlr.2024.100737

Zainuddin Quadri, Erhard Bieberich

引用次数: 0

A facile assay for zDHHC palmitoyl transferase activation elucidates effects of mutation and modification. 对zDHHC棕榈酰转移酶激活的一种简易试验阐明了突变和修饰的影响。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2025-01-10 DOI: 10.1016/j.jlr.2025.100743

Naoko Adachi, Douglas T Hess, Takehiko Ueyama

{"title":"A facile assay for zDHHC palmitoyl transferase activation elucidates effects of mutation and modification.","authors":"Naoko Adachi, Douglas T Hess, Takehiko Ueyama","doi":"10.1016/j.jlr.2025.100743","DOIUrl":"10.1016/j.jlr.2025.100743","url":null,"abstract":"At least 10% of proteins constituting the human proteome are subject to S-acylation by a long-chain fatty acid, thioesterified to a Cys thiol side chain. Fatty S-acylation (prototypically, S-palmitoylation) operates across eukaryotic phylogeny and cell type. S-palmitoylation is carried out in mammalian cells by a family of 23-24 dedicated zDHHC palmitoyl transferase enzymes, and mutation of zDHHCs is associated with a number of human pathophysiologies. Activation of the zDHHCs by auto-S-palmitoylation, the transthioesterification of the active site Cys by fatty acyl coenzyme A, is the necessary first step in zDHHC-mediated protein S-palmitoylation. Most prior in vitro assessments of zDHHC activation have utilized purified zDHHCs, a time- and effort-intensive approach, which removes zDHHCs from their native membrane environment. We describe here a facile assay for zDHHC activation in native membranes. We overexpressed hemagglutinin-tagged wild-type or mutant zDHHCs in cultured HEK293 cells and prepared a whole membrane fraction, which was incubated with fluorescent palmitoyl CoA (NBD-palmitoyl-CoA) followed by SDS-PAGE, fluorescence imaging, and Western blotting for hemagglutinin. We show by mutational analysis that, as assayed, zDHHC auto-S-palmitoylation by NBD-palmitoyl-CoA is limited to the active site Cys. Application of the assay revealed differential effects on zDHHC activation of posttranslational zDHHC modification and of zDHHC mutations associated with human disease, in particular cancer. Our assay provides a facile means of assessing zDHHC activation, and thus of differentiating the effects of zDHHC mutation and posttranslational modification on zDHHC activation versus secondary effects on zDHHC functionality including altered zDHHC interaction with substrate palmitoyl-proteins.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100743"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971204","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

Detecting white adipose tissue browning in mice with in vivo R₂∗ mapping at 9.4T MRI. 在9.4T MRI上用体内R2*作图检测小鼠白色脂肪组织褐变。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-19 DOI: 10.1016/j.jlr.2024.100735

Qiaoling Zhong, Hongsheng Liu, Yanqiu Feng, Xiuwei Jiao, Yuanbo Yang, Daming Zhang, Qian Wang, Zoheb Ahasan, Andrew Z Li, Chong Wee Liew, Zimeng Cai, Zaiyi Liu, Kejia Cai

{"title":"Detecting white adipose tissue browning in mice with in vivo R2∗ mapping at 9.4T MRI.","authors":"Qiaoling Zhong, Hongsheng Liu, Yanqiu Feng, Xiuwei Jiao, Yuanbo Yang, Daming Zhang, Qian Wang, Zoheb Ahasan, Andrew Z Li, Chong Wee Liew, Zimeng Cai, Zaiyi Liu, Kejia Cai","doi":"10.1016/j.jlr.2024.100735","DOIUrl":"10.1016/j.jlr.2024.100735","url":null,"abstract":"White adipose tissue (WAT) browning is considered a promising strategy to combat obesity and related metabolic diseases. Currently, fat-water fraction (FWF) has been used as a marker for the loss of lipids associated with WAT browning. However, FWF may not be sensitive to metabolic changes and cannot specifically reflect iron-regulated metabolism during browning. Here, we report a noninvasive preclinical imaging approach based on iron content detected by R2∗ mapping to assess in vivo WAT browning in mice. In this study, we investigated the browning of inguinal white adipose tissue (iWAT) induced by long-term CL-316,243 (CL) drug stimulation in mice. We quantified the changes in R2∗, FWF, uncoupling protein 1 (UCP1) expression, and iron content. The iWAT of all mice was dissected for H&E staining and immunohistochemistry for the absorbance of UCP1 and iron content. In in vivo experiments, a significant increase in R2∗ and a decrease in FWF were observed in iWAT after 7 days of CL administration compared with the saline-treated and the baseline groups. Accordingly, in ex vivo experiments, UCP1 expression and the total iron content in iWAT significantly increased after 7 days of CL stimulation. By pooling all mice data, the UCP1 expression level of iWAT and iron content was found to be highly correlated with R2∗ and inversely correlated with FWF. Taken together, R2∗ may serve as a potential imaging biomarker for assessing WAT browning, which provides a new diagnostic and therapeutic evaluation tool for metabolic diseases.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100735"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872243","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

Small molecule-driven LKB1 deacetylation is responsible for the inhibition of hepatic lipid response in NAFLD. 小分子驱动的LKB1去乙酰化是NAFLD中抑制肝脏脂质反应的原因。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2025-01-02 DOI: 10.1016/j.jlr.2024.100740

Weiwei Qin, Yu Ding, Wenhao Zhang, Lu Sun, Jianping Weng, Xueying Zheng, Sihui Luo

{"title":"Small molecule-driven LKB1 deacetylation is responsible for the inhibition of hepatic lipid response in NAFLD.","authors":"Weiwei Qin, Yu Ding, Wenhao Zhang, Lu Sun, Jianping Weng, Xueying Zheng, Sihui Luo","doi":"10.1016/j.jlr.2024.100740","DOIUrl":"10.1016/j.jlr.2024.100740","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a progressive condition characterized by ectopic fat accumulation in the liver, for which no FAD-approved drugs currently exist. Emerging evidence highlights the role of liver kinase B1 (LKB1), a key metabolic regulator, has been proposed in NAFLD, particularly in response to excessive nutrient levels. However, few agents have been identified that can prevent the progression of nonalcoholic steatohepatitis (NASH) by targeting LKB1 deacetylation. Through comprehensive screening of our in-house chemical library, we identified tranilast, a small molecule with remarkable inhibitory efficacy against lipid deposition induced by palmitic acid/oleic acid (PO). In this study, we investigated the novel biological function and mechanism of tranilast in regulating hepatic lipid response in NAFLD, focusing on its role in LKB1 deacetylation within hepatocytes. Our findings demonstrate that tranilast effectively reduced hepatic steatosis, inflammation, and fibrosis in NASH models induced by high-fat and high-cholesterol (HFHC) and methionine choline-deficient (MCD) diets. Mechanistic analysis using RNA sequencing revealed that tranilast mitigated hepatic lipid response by promoting LKB1 deacetylation and activating AMPK. Notably, in vivo experiments showed that the beneficial effects of tranilast in MCD diet-induced NASH model were reversed by the compound C (C-C), a known AMPK inhibitor, confirming that tranilast's effects on hepatic lipid response are mediated through the AMPK pathway. In summary, tranilast inhibits hepatic lipid response in NAFLD through LKB1 deacetylation, providing robust experimental evidence for the role of LKB1 in NAFLD. These findings position tranilast as a promising therapeutic candidate for the pharmacological management of metabolic diseases.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100740"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927374","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

Endogenous and fluorescent sterols reveal the molecular basis for ligand selectivity of human sterol transporters. 内源性和荧光甾醇揭示了人类甾醇转运体的配体选择性的分子基础。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-31 DOI: 10.1016/j.jlr.2024.100738

Laura Depta, Hogan P Bryce-Rogers, Nienke J Dekker, Anna Wiehl Bønke, Nicolò Camporese, Mingxing Qian, Yuanjian Xu, Douglas F Covey, Luca Laraia

{"title":"Endogenous and fluorescent sterols reveal the molecular basis for ligand selectivity of human sterol transporters.","authors":"Laura Depta, Hogan P Bryce-Rogers, Nienke J Dekker, Anna Wiehl Bønke, Nicolò Camporese, Mingxing Qian, Yuanjian Xu, Douglas F Covey, Luca Laraia","doi":"10.1016/j.jlr.2024.100738","DOIUrl":"10.1016/j.jlr.2024.100738","url":null,"abstract":"Sterol transport proteins (STPs) play a pivotal role in cholesterol homeostasis and therefore are essential for healthy human physiology. Despite recent advances in dissecting functions of STPs in the human cell, there is still a significant knowledge gap regarding their specific biological functions and a lack of suitable selective probes for their study. Here, we profile fluorescent steroid-based probes across ten STPs, uncovering substantial differences in their selectivity, aiding the retrospective and prospective interpretation of biological results generated with those probes. These results guided the establishment of an STP screening panel combining diverse biophysical assays, enabling the evaluation of 42 steroid-based natural products and derivatives. Combining this with a thorough structural analysis revealed the molecular basis for STP-specific selectivity profiles, leading to the uncovering of several new potent and selective Aster-B inhibitors and supporting the role of this protein in steroidogenesis.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100738"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921907","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

Alterations in LDL and HDL after an ischemic stroke associated with carotid atherosclerosis are reversed after 1 year. 缺血性卒中合并颈动脉粥样硬化后LDL和HDL的改变在1年后逆转。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-31 DOI: 10.1016/j.jlr.2024.100739

Núria Puig, Pol Camps-Renom, Martin Hermansson, Ana Aguilera-Simón, Rebeca Marín, Olga Bautista, Noemi Rotllan, Nerea Blanco-Sanroman, Maria Constanza Domine, Katariina Öörni, José Luis Sánchez-Quesada, Sonia Benitez

{"title":"Alterations in LDL and HDL after an ischemic stroke associated with carotid atherosclerosis are reversed after 1 year.","authors":"Núria Puig, Pol Camps-Renom, Martin Hermansson, Ana Aguilera-Simón, Rebeca Marín, Olga Bautista, Noemi Rotllan, Nerea Blanco-Sanroman, Maria Constanza Domine, Katariina Öörni, José Luis Sánchez-Quesada, Sonia Benitez","doi":"10.1016/j.jlr.2024.100739","DOIUrl":"10.1016/j.jlr.2024.100739","url":null,"abstract":"Approximately, 20% of ischemic strokes are attributed to the presence of atherosclerosis. Lipoproteins play a crucial role in the development of atherosclerosis, with LDL promoting atherogenesis and HDL inhibiting it. Therefore, both their concentrations and their biological properties are decisive factors in atherosclerotic processes. In this study, we examined the qualitative properties of lipoproteins in ischemic stroke patients with carotid atherosclerosis. Lipoproteins were isolated from the blood of healthy controls (n = 27) and patients with carotid atherosclerosis (n = 64) at 7 days and 1 year postischemic stroke. Compared to controls, patients' LDL 7 days poststroke showed increased levels of apoC-III, triacylglycerol, and ceramide, along with decreased cholesterol and phospholipid content. LDL from patients induced more inflammation in macrophages than did LDL from controls. HDL isolated from patients 7 days after stroke showed alterations in the apolipoprotein cargo, with reduced levels of apoA-I and increased levels of apoA-II, and apoC-III compared to controls. Patients' HDL also showed a higher electronegative charge than that of controls and partially lost its ability to counteract the modification of LDL and the inflammatory effects of modified LDL. One year after stroke onset, the composition of patients' LDL and HDL resembled those of the controls. In parallel, LDL and HDL gained positive charge, LDL became less prone to oxidation and aggregation, and HDL regained protective properties. In conclusion, LDL and HDL in ischemic stroke patients with carotid atherosclerosis exhibited alterations in composition and function, which were partially reversed 1 year after stroke.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100739"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921904","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

Resolving lipoxin A₄: Endogenous mediator or exogenous anti-inflammatory agent? 解析脂素A4：内源性介质还是外源性抗炎剂？

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1016/j.jlr.2024.100734

Reagan M McGuffee, Matthew A Luetzen, David A Ford

引用次数: 0

Microglial activation and hypothalamic structural plasticity in HFD obesity: insights from semaglutide and minocycline. HFD肥胖的小胶质细胞激活和下丘脑结构可塑性：来自Semaglutide和Minocycline的见解。

IF 5 2区医学

Journal of Lipid Research Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1016/j.jlr.2024.100736

Xi Rong, Fang Wei, Yuqi Jiang, Qintao Ma, Dongmei Wang, Jie Shen

{"title":"Microglial activation and hypothalamic structural plasticity in HFD obesity: insights from semaglutide and minocycline.","authors":"Xi Rong, Fang Wei, Yuqi Jiang, Qintao Ma, Dongmei Wang, Jie Shen","doi":"10.1016/j.jlr.2024.100736","DOIUrl":"10.1016/j.jlr.2024.100736","url":null,"abstract":"High-fat diet (HFD)-induced microglial activation contributes to hypothalamic inflammation and obesity, but the mechanisms linking microglia to structural changes remain unclear. This study explored the role of microglia in impairing hypothalamic synaptic plasticity in diet-induced obesity mice and evaluated the therapeutic potential of semaglutide (Sema) and minocycline (MI). Six-week-old C57BL/6J mice were divided into low-fat diet and HFD groups. At week 30, the HFD-fed mice were treated daily with Sema or MI for six weeks. Confocal microscopy assessed hypothalamic dendritic spines, synaptic organization, and microglia-synapse interactions. We also analyzed microglial morphology, CD68/CD11b colocalization with Iba-1, synaptic marker expression, and phagocytosis-related pathways (C1q, C3, CD11b). BV2 microglia were used to examine the direct effects of Sema or MI on microglia and validate the in vivo findings. HFD feeding induced microglial activation, as indicated by increased colocalization of CD68 or synaptophysin and CD11b with Iba-1, along with elevated C1q, C3, and CD11b expression, signaling enhanced synaptic phagocytosis. This was accompanied by reduced hypothalamic dendritic spines, decreased synaptic marker expression, and disrupted excitatory/inhibitory synaptic organization in the melanocortin system, as well as impaired glucose metabolism, disrupted leptin-ghrelin balance, and increased food intake and body weight. Sema and MI treatments reversed the pathological changes of microglial activation and restored hypothalamic synaptic structure, although their effects on synaptic organization and metabolic outcomes differed. Our findings highlight the key role of microglial activation in hypothalamic synaptic impairment in diet-induced obesity models, with Sema and MI possibly offering distinct therapeutic pathways to mitigate these impairments.","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100736"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895320","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