Nature Communications
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2025
·Vol. 16
·期 1
·1-16
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IF 15.7
Peng Wang,Chen Shu,Ma Jingyu,Wei Wenjie,Lin Naixin,Xing Jinchao,Guo Wenjing,Li Heying,Zhang Liang,Chan Kuiming,Yen Andrew,Zhu Guangyu,Yue Jianbo
The interplay between lipid droplets (LDs) and endosomes remains unknown. Here, we screen and synthesize AP1-coumarin, an LD-specific probe, by conjugating a fluorescent dye coumarin to a triazine compound AP1. AP1-coumarin labels all stages of LDs in live cells and markedly induces the accumulation of enlarged RAB5-RAB7 double-positive intermediate endosomes. The AP1-coumarin-labeled LDs contact these intermediate endosomes, with some LDs even being engulfed in them. When LD biogenesis is inhibited, the ability of AP1-coumarin to label LDs is markedly reduced, and the accumulation of enlarged intermediate endosomes is abolished. Moreover, blocking the biogenesis of LDs decreases the number of late endosomes while increasing the number of early endosomes and inhibits the endosomal trafficking of low-density lipoprotein (LDL) and transferrin. Correspondingly, interference with RAB5 or RAB7, either through knockdown or using dominant-negative mutants, inhibits LD catabolism, whereas the expression of a RAB7 constitutively active mutant accelerates LD catabolism. Additionally, CCZ1 knockdown not only induces the accumulation of intermediate endosomes but also inhibits LD catabolism. These results collectively suggest that LDs and endosomes interact and influence each other’s functions, and endosomal trafficking participates in the catabolic process of LDs to maintain lipid homeostasis.
研究领域:
细胞生物学
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脂质代谢
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Su Borui,Gao Dong,Xin Nini,Wu Kai,Yang Mei,Jiang Shichao,Zhang Yusheng,Ding Jie,Wu Chengheng,Sun Jing,Wei Dan,Fan Hongsong,Guo Zhenzhen
Lipid droplets (LDs) participating in various cellular activities and are increasingly being emphasized. Fluorescence imaging Provides powerful tool for dynamic tracking of LDs, however, most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield (PLQY), poor photostability and tedious washing procedures. Herein, a novel yellow-emissive carbon dot (OT-CD) has been synthesized conveniently with high PLQY up to 90%. Besides, OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2, which is much higher than most LDs probes. These characters enable OT-CD high brightness, stable and wash-free LDs probing, and feasible for in vivo imaging. Then, detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded, including ferroptosis and other diseases processes. Furthermore, fast whole imaging of zebrafish and identified LD enrichment in injured liver indicate its further feasibility for in vivo application. In contrast to the reported studies to date, this approach provides a versatile conventional synthesis system for high performance LDs targeting probes, combing the advantages of easy and high yield production, as well as robust brightness and stability for long-term imaging, facilitating investigations into organelle interactions and LD-associated diseases.
研究领域:
材料科学
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生物医学工程
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细胞生物学
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成像科学
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
·
2022
·Vol. 70
·期 1
·68-75
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IF 1.753
Yuanyuan Cui,Yaoyang Meng,Yun Hu,Yuqi Chen,Yixian Yang,Min Fang,Cun Li,Weiju Zhu
A novel fluorescent probe, LCH , based on dicyanisophorone and carbazole, was prepared for the visual detection of Cu 2+ . The probe LCH could recognize Cu 2+ by fluorescence quenching in EtOH/H 2 O (1/4, v/v) solution, which could be easily identified under the 365 nm UV lamp, and the detection limit was as low as 0.785 μM. The recognition mechanism of probe LCH with Cu 2+ was determined by combining 1 H NMR titration, MS, and theoretical calculations. Practical application experiments showed that probe LCH could be used to detect Cu 2+ in the test strip experiments. Cell imaging experiments showed that the probe LCH owned good cell permeability and could be applied to the imaging of Cu 2+ in HepG2 cells. In addition, fluorescence colocalization experiments showed that LCH could target lipid droplets. These results indicate that the probe LCH will have a good application prospect in environmental detection and clinical medicine.
研究领域:
分析化学
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生物医学
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环境科学
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产品关联
DOI
高影响因子
RSC Advances
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2021
·Vol. 11
·期 14
·8250-8254
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IF 3.361
Huiying Chen,Jianzhi Zhao,Junzhi Lin,Baoli Dong,Hui Li,Bing Geng,Mei Yan
Lipid droplets (LDs) are storage organelles at the centre of lipid and energy homeostasis, which act as vital hubs of cellular metabolism and the key to maintaining lipid and energy homeostasis. We synthesized a new two-photon fluorescent probe (CIV) that could detect the viscosity of lipid droplets. The probe is constructed via the typical ICT system of D–π–A using carbazole as the donor and imidazole as the acceptor. With the increase in viscosity from PBS to 99% glycerol, the fluorescence intensity of CIV increased by 13-fold, showing sensitivity and specificity towards viscosity. In addition, CIV showed low toxicity and excellent biocompatibility in cytotoxicity tests, and was successfully used for living cell LD imaging. Taken together, the results widen the way for the development of novel fluorescent probe-based the visualization LDs and detection in solutions, physiology and pathology.
研究领域:
生物化学
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细胞生物学
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医学影像学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 18
·6626
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IF 4.6
Lin Shan,Xuewei Li,Xiuli Zheng,Jiasheng Wu,Haohui Ren,Weimin Liu,Pengfei Wang
As a class of highly dynamic organelles, lipid droplets (LDs) are involved in numerous physiological functions, and the changes in polarity of LDs are closely related to a variety of diseases. In this work, we developed two polarity-sensitive fluorescent probes (CC-CH and CC-Cl) based on curcumin analogs. CC-CH and CC-Cl with a donor–acceptor–donor (D–A–D) structure exhibited the property of intramolecular charge transfer (ICT); thus, their fluorescence emissions were significantly attenuated with increasing ambient polarity. Cell experiments indicated that CC-CH and CC-Cl showed excellent photostability, a low cytotoxicity, and a superior targeting ability regarding LDs. After treatment with oleic acid (OA) and methyl-β-cyclodextrin (M-β-CD), the polarity changes of LDs in living cells could be visualized by using CC-CH and CC-Cl. In addition, CC-CH and CC-Cl could monitor polarity changes of LDs in different pathological processes, including inflammatory responses, nutrient deprivation, and H2O2-induced oxidative stress. Therefore, CC-CH and CC-Cl are promising potential fluorescent probes for tracking intracellular LD polarity changes.Keywords:polarity-sensitive;lipid droplet targeted;fluorescent probes;cell imaging
研究领域:
生物化学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
OSTEOARTHRITIS AND CARTILAGE
·
2024
·
IF 7.2
Jia Yu,Qian Liu,Yuejiao Zhang,Lingfeng Xu,Xiaohua Chen,Feng He,Mian Zhang,Hongxu Yang,Shibing Yu,Xin Liu,Yaoping Wu,Meiqing Wang
Objective Abnormal mechanical stress is intimately coupled with osteoarthritis (OA). Microtubules play a vital role in the regulation of mechanotransduction and intracellular transport. The purpose of the present study was to investigate the impact of stress-induced microtubule impairment on intracellular transport and lipid droplet (LD) accumulation in chondrocytes. Method Rats were subjected to unilateral anterior crossbite (UAC), which is inducible for degeneration of temporomandibular joint (TMJ) cartilage. Chondrocytes derived from rat TMJ cartilage were subjected to fluid flow shear stress (FFSS) and analyzed via LC MS/MS-based proteomics. The microtubule destabilization agent nocodazole and/or the microtubule stabilizer docetaxel were used in the UAC and FFSS models. Results In both FFSS- and UAC-treated chondrocytes, decreased acetylated α-Tubulin (ac-Tubulin) expression and LD accumulation were observed. Proteomic data revealed increased levels of the LD-associated protein perilipin 3 (Plin3) and decreased levels of cytoskeleton components in FFSS-treated chondrocytes. Live-cell imaging revealed that the colocalization of LDs with lysosomes was significantly decreased after FFSS treatment. Impairment of microtubules by nocodazole reduced the protein level of ac-Tubulin and disrupted the Hsc70-mediated interaction between Plin3 and Lamp2a, as shown by co-IP assays. In contrast, docetaxel reversed the suppression of ac-Tubulin expression, reduced the accumulation of LDs, and decreased the expression of Plin3 in chondrocytes exposed to FFSS and UAC, and docetaxel ameliorated UAC-induced osteoarthritic lesions in the TMJ cartilage. Conclusion Microtubule impairment under aberrant stress conditions disrupts intracellular transport and blocks lipophagy, causing LD accumulation in chondrocytes. Microtubule stabilization could be a new approach for treating stress-induced cartilage degeneration.
研究领域:
医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
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2020
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IF 4.613
Kang-Nan Wang,Xiang-Jun Peng,Yi Li,Hai-Tao Tang,Ying-Ming Pan,Liang He
In addition to being associated with energy supply, lipid droplets (LDs) play vital roles in many other important physiological and some pathological processes. Fluorescent probes are useful tools for studying the biological functions of LDs. In this study, we develop three new highly fluorescent LD-specific bioprobes, which can be excited by one- and two-photon, with favorable biocompatibility. They have little crosstalk with some commonly used commercially-available green- and red-emissive probes, such as BODIPY 493/503, MitoTracker Red CMXRos (MTR) and LysoTracker Red DND-99 (LTR), thus allowing the simultaneous multicolor imaging. Notably, one of the probes, BIP-1 , has superior photostability and allows excellent 3D imaging of cellular LDs. BIP-1 can be used to monitor the number and morphological changes of LDs, and the interactions of LDs with other organelles (e.g. mitochondria) under specific physiological conditions (e.g. starvation). Overall, BIP-1 is a promising alternative fluorescent bioprobe for live-cell LD-specific imaging and long-term tracking during LD-related research.
研究领域:
细胞生物学
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生物成像
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分子生物学
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产品关联
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2025
·
IF 7.7
Wenxian Chen,Tongzhu Jin,Yilin Xie,Changsheng Zhong,Huiying Gao,Lei Zhang,Jin Ju,Ting Cheng,Mengyang Li,Huifang Wang,Zhenbo Yang,Qin Deng,Zhimin Du,Haihai Liang
Background and Purpose Emerging evidence indicated that the excessive lipid droplets (LDs) accumulation and lipotoxicity play a significant role in the development of diabetic cardiomyopathy (DCM), yet the regulatory mechanisms governing the function of cardiac LDs are still unknown. Lipophagy has been shown to be involved in the maintenance of LDs homeostasis. The objective of this study was to explore the mechanism of lipophagy in cardiomyocytes and investigate whether berberine could mitigate DCM by modulating this pathway. Experimental Approach Bioinformatics analysis identified disorders of lipid metabolism and autophagy in DCM. To carry out further research, db/db mice were utilized. Furthermore, H9C2 cells treated with palmitic acid were employed as a model to explore the molecular mechanisms involved in myocardial lipotoxicity. Key Results The results showed that lipophagy was impaired in DCM. Mechanistically, sirtuin 3 (SIRT3) was demonstrated to regulate lipophagy in cardiomyocytes. SIRT3 was down-regulated in DCM. Conversely, activation of SIRT3 by the activator nicotinamide riboside (NR) could promote lipophagy to alleviate PA-induced lipotoxicity in H9C2 cells. Moreover, berberine administration markedly mitigated diabetes-induced cardiac dysfunction and hypertrophy in db/db mice, which dependent on SIRT3-mediated lipophagy. Conclusion and Implications Collectively, SIRT3 could moderate cardiac lipotoxicity in DCM by promoting lipophagy, suggesting that the regulation of SIRT3-mediated lipophagy may be a promising strategy for treating DCM. The findings indicate that the therapeutic potential of berberine for DCM is associated with lipophagy.
研究领域:
心血管医学
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代谢生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2021
·
IF 7.46
Sayed Mir Sayed,Xiang-Fei Li,Hao-Ran Jia,Samran Durrani,Fu-Gen Wu,Xiaolin Lu
Lipid droplets (LDs) are spherical dynamic subcellular organelles, and play crucial roles in a number of cellular functions, such as lipid metabolism, protein degradation, membrane formation, energy storage, and signal transduction. It is widely recognized that the dysfunction of LDs can lead to many diseases, and hence it is important to monitor the size, distribution, and movement of LDs in living cells. Herein, we report a dibenzothiopene core-based fluorescent probe named triphenylamine dibenzothiophene-S,S-dioxide (TPA-DBTD), which can exhibit aggregation-induced emission (AIE) characteristic and realize selective and wash-free imaging of LDs in live cells. Most importantly, this probe can efficaciously track the dynamic changes of LDs including lipophagy (an autophagic process that is responsible for the degradation of lipids) in live mammalian cells and stain LDs in fungi. Hence, we believe that TPA-DBTD with high photostability, good biocompatibility, AIE characteristic, and LD staining ability in diverse biological systems (mammalian cells and microorganisms) can find practical applications in the fields of biomedical science, cell biology, and diagnosis of LDs-associated diseases.
研究领域:
生物医学
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细胞生物学
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诊断学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2022
·
IF 0
Yingying Jing,Guoyong Liu,Chenshuang Zhang,Bin Yu,Jian Sun,Danying Lin,Junle Qu
Lipid droplets (LDs), a dynamic organelle, are of vital importance in regulating the storage of neutral lipids and energy homeostasis. The aberrant expression of LDs is found to be highly associated with diverse metabolic diseases. Thus, detecting and monitoring LDs are essential to study the pathological and physiological processes of LDs in living bodies. However, it remains challenging to obtain suitable imaging probes to track LDs in vivo. Fortunately, the emergence of carbon dots (CDs), which are fluorescent nanomaterials with good biocompatibility and high stability, has provided us an unprecedented choice. In this work, CDs were synthesized via a solvothermal treatment of commercial reagents, 3-dimethylaminophenol. Interestingly, the prepared CDs show an intense red emission in non-hydrogen-bonding solution and have strong LD-targeting ability without any postmodification of ligands. Moreover, due to their low phototoxicity and excellent photostability, CDs were successfully applied to track the dynamics of LDs in live cells and image LDs in different cell lines and lipid-rich tissues. Overall, this work here proposed an LD-specific red-emitting CD probe, which will be of great value for learning more about LD-associated behaviors and diseases.
研究领域:
细胞生物学
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医学影像学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Ke Xue,Yongfei Zhao,Saidong Sun,Yuanhang Li,Jiankang Liang,Zhengjian Qi
Severe ferroptosis is a non-apoptotic iron-dependent cell death pathway, and extreme hypoxia and anomalous iron metabolism in tumors critically suppress the efficacy of ferroptosis therapy. Overcoming tumor hypoxia while facilitating ferroptosis is an extremely challenging task. Herein, the photosensitizer named BOTTQ with specific targeting of lipid droplet (LD) was synthesized by increasing the tail chain length of triphenylamine. The addition of alkoxy chains optimized the molecular structure and fostered inter-system crossing and type I reactive oxygen species (ROS) generation. Besides, BOTTQ yielded large amounts of type I ROS under light excitation oxidize efficiently polyunsaturated fatty acids in lipid monolayer of LD and contribute to the formation of ferroptosis substrate. Meanwhile, the generation of type I ROS accelerated the Fenton reaction, thus effectively boosting the occurrences of ferroptosis. Furthermore, the successful encapsulation of BOTTQ into DSPE-PEG-MAL material not only elevates the stable type of nanoparticle colloids, but the MAL moiety can deplete the functional thiols of glutathione in a mild environment, which leads to glutathione failure and facilitates ferroptosis. Thus tumor-specific ferroptosis-inducing strategy offers a universally applicable therapy with the capacity to enhance type I ROS production and effectively contain tumorigenesis.
研究领域:
生物医学工程
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肿瘤学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2024
·
IF 3.7
Shuang Wang,Bingbing Zhang,John Mauck,Juan J. Loor,Wenwen Fan,Yan Tian,Tianjiao Yang,Yaqi Chang,Meng Xie,Ben Aernouts,Wei Yang,Chuang Xu
ABSTRACT Hepatocellular lipid accumulation characterizes fatty liver in dairy cows. Lipid droplets (LD), specialized organelles that store lipids and maintain cellular lipid homeostasis, are responsible for the ectopic storage of lipids associated with several metabolic disorders. In recent years, non-ruminant studies have reported that LD-mitochondria interactions play an important role in lipid metabolism. Due to the role of diacylglycerol acyltransferase isoforms (DGAT1 and DGAT2) in LD synthesis, we explored mechanisms of mitochondrial fatty acid transport in ketotic cows using liver biopsies and isolated primary hepatocytes. Compared with healthy cows, cows with fatty liver had massive accumulation of LD and high protein expression of the triglyceride (TAG) synthesis-related enzymes DGAT1 and DGAT2, LD synthesis-related proteins perilipin 2 (PLIN2) and perilipin 5 (PLIN5), and the mitochondrial fragmentation-related proteins dynamin-related protein 1 (DRP1) and fission 1 (FIS1). In contrast, factors associated with fatty acid oxidation, mitochondrial fusion and mitochondrial electron transport chain complex were lower compared with those in the healthy cows. In addition, transmission electron microscopy revealed significant contacts between LD-mitochondria in liver tissue from cows with fatty liver. Compared with isolated cytoplasmic mitochondria, expression of carnitine palmitoyl transferase 1A (CPT1A) and DRP1 was lower, but mitofusin 2 (MFN2) and mitochondrial electron transport chain complex was greater in isolated peridroplet mitochondria from hepatic tissue of cows with fatty liver. In vitro data indicated that exogenous free fatty acids (FFA) induced hepatocyte LD synthesis and mitochondrial dynamics consistent with in vivo results. Furthermore, DGAT2 inhibitor treatment attenuated the FFA-induced upregulation of PLIN2 and PLIN5 and rescued the impairment of mitochondrial dynamics. Inhibition of DGAT2 also restored mitochondrial membrane potential and reduced hepatocyte reactive oxygen species production. The present in vivo and in vitro results indicated there are functional differences among different types of mitochondria in the liver tissue of dairy cows with ketosis. Activity of DGAT2 may play a key role in maintaining liver mitochondrial function and lipid homeostasis in dairy cows during the transition period.
研究领域:
动物科学
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代谢
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分子生物学
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兽医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）