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Physiological and pathological roles of FATP-mediated lipid droplets in Drosophila and mice retina.

Increasing evidence suggests that dysregulation of lipid metabolism is associated with neurodegeneration in retinal diseases such as age-related macular degeneration and in brain disorders such as Alzheimer's and Parkinson's diseases. Lipid storage organelles (lipid droplets, LDs), accumulate in many cell types in response to stress, and it is now clear that LDs function not only as lipid stores but also as dynamic regulators of the stress response. However, whether these LDs are always protective or can also be deleterious to the cell is unknown. Here, we investigated the consequences of LD a…

Precise Labeling and Tracking of Lipid Droplets in Adipocytes Using a Luminescent ZnSalen Complex.

Designing two-photon probes for precise labeling of lipid droplets (LDs) and monitoring LD dynamics in adipocytes is of great significance to understand LD homeostasis. We herein report that a luminescent metal complex LD-TPZn can specifically image LDs in adipose cells and tissue using one- or two-photon fluorescence microscopy. Importantly, LD-TPZn exhibited higher specificity to LDs than the commercial dyes Nile Red and Bodipy 493/503, probably due to different cellular uptake pathways, that is, clathrin-mediated endocytosis and non-selectively passive diffusion, respectively. More importan…

An ultrastructural study on arrhythmogenic right ventricular dysplasia with special reference to lipid droplets.

Myocardial tissues in arrhythmogenic-right ventricular dysplasia (ARVD), which were surgically resected from the site of origin of ventricular tachycardia (VT), were investigated optically and electron-microscopically. The site of origin was found to be occupied by an abundance of adipose cells. In the marginal zone, lipid droplets were obviously increased in count in the cytoplasm of both myocytes and blood capillary-endothelium, rather more than in distant areas. Lipid droplets in the endothelial cells also occurred at a higher frequency in the ARVD group than in any other myocardial disease…

Sodium-glucose co-transporters (SGLT2) inhibitors prevent lipid droplets formation in vascular inflammation or lipid overload by SGLT2-independent mechanism.

BACKGROUND: The formation of vascular lipid droplets (LDs) induced by vascular inflammation or lipid overload contributes to vascular pathophysiology in diabetes and cardiometabolic diseases, while sodium-glucose co-transporter 2 inhibitors (SGLT2-I) are beneficial in treating these conditions. Thus, we hypothesized that SGLT2-I would directly modify vascular LDs formation during vascular inflammation or lipid overload, and explored underlying mechanisms. METHODS: LDs formation in isolated murine aorta from wild-type or SGLT2-KO animals was induced by either treatment with tumour necrosis fac…

Изучение новых ролей липидных капель и липидного метаболизма в регулировании воспаления и функций мозгового барьера в неврологических заболеваниях.

Барьер мозга крови (BBB) — критическая структура, которая поддерживает гомеостаз мозга, регулируя перенос молекул и защищая его от вредных веществ. Однако в таких неврологических болезнях, как ишемический инсульт, болезнь Альцгеймера, болезнь Паркинсона и множественный склероз, целостность и функция ББД могут быть серьезно подорваны. В этих условиях нарушение BBB приводит к повышению проницаемости, что облегчает нейроинфламмацию, усугубляет нейронные повреждения и ускоряет развитие болезни. Недавние исследования выявили потенциал липозвуковых переносчиков, включая липосомы и липидные капли (LD

Совпадение в аннотации оригинала
The blood-brain barrier (BBB) is a critical structure that maintains the brain's homeostasis by regulating the transport of molecules and pr … ion. Recent research has highlighted the potential of lipid-based carriers, including liposomes and lipid droplets (LDs), in modulating the BBB's integrity and function in various neurological diseases. Liposomes, with their ability to cross the BBB via mechanisms such as receptor-mediated transcytosis and carrier-mediated transport, are emerging as promising ve …

Bioinspired lipid droplets nanoplatform for periodontitis therapy: Integrated antibacterial, mitochondrial repair, and immunomodulatory functions.

Periodontitis, a multifactorial inflammatory disease driven by microbial dysbiosis, dysregulated immunity, and oxidative stress, demands therapeutic strategies that concurrently address interconnected pathological pathways. Here, a biomimetic lipid droplet-based nanoplatform (GA@LDs-CRAMP) is engineered to achieve spatiotemporal coordination of antibacterial, antioxidant, and immunomodulatory functions for the treatment of periodontitis. Constructed using RAW264.7 macrophage-derived lipid droplets (LDs), the GA@LDs-CRAMP system anchors cathelicidin-related antimicrobial peptide (CRAMP) onto LD…

Hepatic stellate cell derived lipid droplets drive protumoral M2 macrophage polarization in hepatocellular carcinoma.

BACKGROUND: During chronic liver injury, hepatic stellate cells (HSCs) lose their vitamin-A-rich lipid droplets (LDs), yet whether these organelles are merely degraded or released via vesicles and functionally relevant remains unclear. We investigated the fate of HSCs LDs and their impact on hepatic macrophage phenotype and hepatocellular carcinoma (HCC) development. METHODS: Chronic liver injury was induced in C57BL/6 mice using carbon tetrachloride (CCl4) for up to 12 weeks. HSCs activation and lipid droplet dynamics were assessed by immunofluorescence, transmission electron microscopy, and…

Lipid droplets promote aberrant liquid-liquid phase separation of alpha-synuclein impairing energy homeostasis.

Alpha-synuclein (αSyn) inclusions are a defining neuropathological feature of Parkinson's disease, but the cellular events that initiate their formation and promote neurotoxicity remain incompletely understood. Aberrant liquid-liquid phase separation has emerged as a potential early step in αSyn dysregulation, yet the physiological triggers and functional consequences of this process are unclear. Here, we show that lipid droplets promote the spontaneous phase separation of wild-type and E46K mutant αSyn into condensates. These condensates sequester lipid droplets and impair their turnover, ind…

Lipid droplets and small extracellular vesicles interplay in Japanese encephalitis virus non-lytic release.

UNLABELLED: Lipid droplets (LDs) and small extracellular vesicles (sEVs) are classically known for lipid metabolism and intercellular communication, respectively. Here, we reveal a mechanistic connection between LD dynamics and sEV-mediated non-lytic release of Japanese encephalitis virus (JEV) from neuronal cells. Using Neuro2A, SHSY-5Y, N9 microglia, and primary cortical neurons, we show that JEV is packaged within sEVs (~200 nm) through an ESCRT-independent, neutral sphingomyelinase 2 (nSMase2)/ceramide-dependent pathway. Virions inside sEVs display a higher JEV premature membrane/membrane …

An electroneutral fluorescent probe for visualization of lipid droplets polarity heterogeneity and NAFLD detection.

Lipid droplets (LDs), omnipresent organelles in nearly all eukaryotic cells, have garnered significant attention in cell biology. Alterations in LD polarity not only signify cellular carcinogenesis but also correlate closely with the severity of nonalcoholic fatty liver disease (NAFLD). Despite their importance, the lack of suitable detection tools has limited research and clinical applications in this area. In this study, we develop LD-PL, an electroneutral fluorescent probe to visualize LDs polarity heterogeneity. Interestingly, LD-PL exhibits exceptional sensitivity to LD polarity variation…

Lipid droplets deposition in perihematoma tissue is associated with neurological dysfunction after intracerebral hemorrhage.

Secondary brain injury following intracerebral hemorrhage (ICH) significantly reduces patients' quality of life due to impaired neurological function. Lipid droplets are implicated in secondary brain injury in various central nervous system diseases. Thus, the role and mechanisms of lipid droplets in secondary brain injury post-ICH require further investigation. We analyzed the changes of genes related to lipid metabolism in brain tissue of ICH mice. Lipid droplets around the hematoma were detected by BODIPY staining. Mice received intraperitoneal injections of Triacsin C (10 mg/kg, once daily…

Mycobacterium abscessus resides within lipid droplets and acquires a dormancy-like phenotype in adipocytes.

Mycobacterium abscessus (M. abscessus) is an emerging, rapidly growing mycobacterium that causes chronic lung infection, particularly in pat … ivo infection model. M. abscessus infected not only the cytosol of adipocytes but also entered host lipid droplets, where it formed intracytoplasmic lipid inclusions in the bacterial cell. To our knowledge, this unique localization has never been reported for M. abscessus or any other mycobacterium. Within host lipid droplets, M. abscessus lost acid-fastness and …

Novel Effect of p-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets.

p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (

Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells.

Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased e

The Role of Cytosolic Lipid Droplets in Hepatitis C Virus Replication, Assembly, and Release.

The hepatitis C virus (HCV) causes chronic hepatitis by establishing a persistent infection. Patients with chronic hepatitis frequently develop hepatic cirrhosis, which can lead to liver cancer-the progressive liver damage results from the host's immune response to the unresolved infection. The HCV replication process, including the entry, replication, assembly, and release stages, while the virus circulates in the bloodstream, it is intricately linked to the host's lipid metabolism, including the dynamic of the cytosolic lipid droplets (cLDs). This review article depicts how this interaction …

Lipid droplets, the Holy Grail of hepatic stellate cells: In health and hepatic fibrosis.

Lipid droplets (LDs) are distinct morphological markers of hepatic stellate cells (HSCs). They are composed of a core of predominantly retinyl esters and triacylglycerols surrounded by a phospholipid layer; the latter harbors perilipins 2, 3, and 5, which help control LD lipolysis. Electron microscopy distinguishes between Types I and II LDs. Type I LDs are surrounded by acid phosphatase-positive lysosomes, which likely digest LDs. LD count and retinoid concentration are modulated by vitamin A intake. Alcohol consumption depletes hepatic retinoids and HSC LDs, with concomitant transformation o…

Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is defined by the abundance of lipid droplets (LDs) in hepatocytes. While historically considered simply depots for energy storage, LDs are increasingly recognized to impact a wide range of biological processes that influence cellular metabolism, signaling, and function. While progress has been made toward understanding the factors leading to LD accumulation (i.e. steatosis) and its progression to advanced stages of NAFLD and/or systemic metabolic dysfunction, much remains to be resolved. SCOPE OF REVIEW: This review covers many facets of …

Revealing lipid droplets evolution at nanoscale under proteohormone stimulation by a BODIPY- hexylcarbazole derivative.

Lipid droplets (LDs) ultrastructure progression under proteohormone stimulation provide valuable clues for understanding conditions associated with obesity and diabetes. Current available LDs probes either alter intra-LDs environments or lack photo-resistance; thus, this research domain is poorly understood. In this work, a N-B-O type BODIPY- hexylcarbazole derivative named BoCz-Lip was rationally designed while achieving specific LDs live-cell targeting. BoCz-Lip showed minimal impact on cell viability as well as internal LDs' protein, triglyceride and cholesterol level. Along with its good p…

Fluorescent redox-dependent labeling of lipid droplets in cultured cells by reduced phenazine methosulfate.

Natural and synthetic phenazines are widely used in biomedical sciences. In dehydrogenase histochemistry, phenazine methosulfate (PMS) is ap … MS (5 μg/mL, 30 min) showed cytoplasmic granules with bright blue fluorescence, which correspond to lipid droplets labeled by the lipophilic methyl-phenazine. After formaldehyde fixation blue-fluorescing droplets could be stained with oil red O. Interestingly, PMS-treated 3T3-L1 adipocytes observed under UV excitation 24 h after labeling showed large lipid dropl …

The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets.

The inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. Here, we show that the INM is an adaptable membrane territory capable of lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets from the INM and is characterized by lipi…