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TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumula

Lipid droplet screen in human hepatocytes identifies TRRAP as a regulator of cellular triglyceride metabolism.

Hepatocytes store triglycerides (TGs) in the form of lipid droplets (LDs), which are increased in hepatosteatosis. The regulation of hepatic LDs is poorly understood and new therapies to reduce hepatosteatosis are needed. We performed a siRNA kinase and phosphatase screen in HuH-7 cells using high-content automated imaging of LDs. Changes in accumulated lipids were quantified with developed pipeline that measures intensity, area, and number of LDs. Selected "hits," which reduced lipid accumulation, were further validated with other lipid and expression assays. Among several siRNAs that resulte…

SEIPIN Isoforms Interact with the Membrane-Tethering Protein VAP27-1 for Lipid Droplet Formation.

SEIPIN proteins are localized to endoplasmic reticulum (ER)-lipid droplet (LD) junctions where they mediate the directional formation of LDs into the cytoplasm in eukaryotic cells. Unlike in animal and yeast cells, which have single SEIPIN genes, plants have three distinct SEIPIN isoforms encoded by separate genes. The mechanism of SEIPIN action remains poorly understood, and here we demonstrate that part of the function of two SEIPIN isoforms in Arabidopsis (Arabidopsis thaliana), AtSEIPIN2 and AtSEIPIN3, may depend on their interaction with the vesicle-associated membrane protein (VAMP)-asso

Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue.

Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation…

Заражение хламидией трахоматисом ведет к определенным изменениям в Lipid Dropple Proteome в эпиталиальных клетках.

Внутриклеточный бактерий хламидиотрахоматис является одним из основных патогенов человека и главной причиной гениталий и окулярных заболеваний. Во время внутриклеточного цикла C. trachomatis реплицирует внутри мембранного вакуола, названного «исключением». Приобретение липидов (и других питательных веществ) из клетки-носителя является важнейшим шагом в хламидиальном воспроизведении. Липидные капли (LD) являются вездесущими нейтральными органами хранения с высоким содержанием липидов, созданными на основе ER, в окружении моноубийцами с фосфолипидом и связанными с ними белками. Предыдущие исслед

Совпадение в аннотации оригинала
The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During … on of lipids (and other nutrients) from the host cell is a critical step in chlamydial replication. Lipid droplets (LD) are ubiquitous, ER-derived neutral lipid-rich storage organelles surrounded by a phospholipids monolayer and associated proteins. Previous studies have shown that LDs accumulate at the periphery of, and eventually translocate into, the chlamydi …

Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2.

Hyperosmolarity (HO) imposes a remarkable stress on membranes, especially in tissues in direct contact with the external environment. Our efforts were focused on revealing stress-induced lipid changes that precede the inflammatory cytokine response in human corneal epithelial cells exposed to increasing osmolarity. We used a lipidomic analysis that detected significant and systematic changes in the lipid profile, highly correlated with sodium concentrations in the medium. Ceramides and triglycerides (TGs) were the most-responsive lipid classes, with gradual increases of up to 2- and 3-fold, re

Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity.

Adipose tissue is now recognized for its major role in the control of energy metabolism and insulin sensitivity. We review here the human lipodystrophies, that are rare conditions in which total or partial fat loss is associated with severe lipid and glucose abnormalities leading to diabetes with early cardiovascular and hepatic complications. The genetic origin of a number of human lipodystrophies has been recently unraveled, emphasizing the importance of proteins of previously unknown or unexpected functions. Major adipose functions were also illuminated when studying acquired forms of lipod

Chanarin-Dorfman syndrome: deficiency in CGI-58, a lipid droplet-bound coactivator of lipase.

Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disease of lipid metabolism; it is associated with congenital ichthyosis typed as non-bullous congenital ichthyosiform erythroderma (NCIE). CDS is characterized by the presence of an abnormally large number of cytosolic lipid droplets containing triacylglycerol (TG) in various tissues such as the skin, liver, and leukocytes. Mutations in the CGI-58 (also called ABHD5) gene encoding a 39-kDa protein of the alpha/beta hydrolase domain subfamily have been shown to be responsible for this disorder. In adipocytes, CGI-58 is involved in T…

Placental lipid droplets and histone marks reveal a metabolic-epigenetic phenotype in the BTBR mouse model of autism.

INTRODUCTION: The placenta shapes fetal brain development through metabolic and epigenetic regulation. The BTBR T+ Itpr3tf/J (BTBR) mouse pr … ylation). RESULTS: Trophoblast giant cells in BTBR placentas exhibit a marked shift toward smaller lipid droplets, indicating altered lipid remodeling and fragmentation without a reduction in total lipid storage capacity. PLA2G4E displayed conserved, compartment-specific localization across placental layers. At the chromatin level, BTBR placentas showed increas …

Reduction of Lipid Droplets Modulates the Injury Response and Enhances CNTF-Induced Axon Regeneration Following Optic Nerve Crush.

Disruption of lipid metabolism occurs in both the retina and optic nerve following optic nerve crush (ONC); however, whether the regulation of lipid droplets (LDs) influences the survival and function of retinal ganglion cells (RGCs) remains largely elusive. Here, we identified the distribution of LDs in the retina and optic nerve of ONC mice, and A922500, a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), was applied to investigate the effect of suppressing LD biogenesis on RGC survival and visual function. The results showed that LDs were localized in Tuj1-positive cells with…

A single fluorescent probe for dual-color imaging and polarity precise analysis in lipid droplets and endoplasmic reticulum.

BACKGROUND: Elaborating the subcellular polarity is pivotal for pathophysiological research and early disease diagnosis. Despite its significance, achieving simultaneous two-color fluorescence imaging and quantitative analysis of polarity across multiple organelles remains challenging. This limitation primarily stems from the lack of single fluorescent (SF) probes capable of such precise and multifaceted functionality. RESULTS: We introduce a novel SF probe LE-TPA, designed for concurrent dual-color imaging and precise polarity determination in lipid droplets (LDs) and the endoplasmic reticul…

Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes.

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis ( P =0.029, log-rank …

Accumulation of lipid droplets induced by Listeria monocytogenes in macrophages: implications for survival and evasion of innate immunity.

Listeriosis, caused by Listeria monocytogenes (L.m.), poses a significant public health concern as one of the most severe foodborne diseases. The pathogenesis of L.m. involves critical steps such as phagosome rupture and escape upon internalization. Throughout infection, L.m. influences various host processes, including lipid metabolism pathways, yet the role of lipid droplets (LDs) remains unclear. Here, we reported a rapid, time-dependent increase in LD formation in macrophages induced by L.m. LD biogenesis was found to be dependent on L.m. viability and virulence genes, particularly on the …

Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets.

Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl…

Loss of Hepatic Surf4 Depletes Lipid Droplets in the Adrenal Cortex but Does Not Impair Adrenal Hormone Production.

The adrenal gland produces steroid hormones to play essential roles in regulating various physiological processes. Our previous studies show … uction was affected in Surf4LKO mice. We observed that lacking hepatic Surf4 essentially eliminated lipid droplets and significantly reduced cholesterol levels in the adrenal gland; however, plasma levels of aldosterone and corticosterone were comparable in Surf4LKO and the control mice under basal and stress conditions. Further analysis revealed that mRNA level …

Effects of progesterone on the lipolysis of lipid droplets and prostaglandin E2 synthesis in murine cervical epithelial cells.

Previous studies demonstrated that progesterone (P4) can promote prostaglandin (PG) E2 production; however, how P4 mediates the synthesis of … se (ERK) 1/2 and hormone-sensitive lipase (HSL) ratios; (3) a significant decrease in the number of lipid droplets (LDs) and fatty acid content within LDs in epithelial cells; and (4) enhanced arachidonic acid and PGE2 levels in cells compared with the control (0nM P4) group (P<0.01 for all findings). In contrast, the PKA inhibitor H89 contributed to significant …

A sensitive bio-probe for tracking lipid droplets with large Stokes shift and its application in cell imaging.

Lipid droplets (LDs) including triacylglycerols and cholesteryl esters are applied for protein transformation and protein maturation in living bodies, which have an important effect on lipid metabolism, homeostasis, and interactions with other organelles. The imbalance of LDs could lead to many serious diseases including insulin resistance, cancer, obesity, liver disease, cardiovascular disease, and neurodegenerative disease. The diameter distribution of LDs is quite extensive from 100 nm to 100 µm. Herein, we designed and constructed a novel organic bio-probe TzAr-N for LDs cell imaging with …

Hepatic Expression of the Serine Palmitoyltransferase Subunit Sptlc2 Reduces Lipid Droplets in the Liver by Activating VLDL Secretion.

OBJECTIVE: Ceramide is a signaling molecule that contributes to insulin resistance and hepatosteatosis. In the present study, we activated de novo ceramide synthesis by inducing the hepatic expression of Sptlc2 to investigate the role of ceramide in glucose and lipid metabolism. METHODS: We first constructed an adenovirus containing Sptlc2 (AdSptlc2), which encodes a major catalytic subunit of serine palmitoyltransferase (SPT). We then infected hepatocytes and mice fed a regular diet with AdSptlc2 to activate de novo ceramide biosynthesis. The liver-specific effects of ceramide biosynthesis o

Coordination Among Lipid Droplets, Peroxisomes, and Mitochondria Regulates Energy Expenditure Through the CIDE-ATGL-PPARα Pathway in Adipocytes.

Metabolic homeostasis is maintained by an interplay among tissues, organs, intracellular organelles, and molecules. Cidea and Cidec are lipid droplet (LD)-associated proteins that promote lipid storage in brown adipose tissue (BAT) and white adipose tissue (WAT). Using ob/ob/Cidea-/- , ob/ob/Cidec-/- , and ob/ob/Cidea-/-/Cidec-/- mouse models and CIDE-deficient cells, we studied metabolic regulation during severe obesity to identify ways to maintain metabolic homeostasis and promote antiobesity effects. The phenotype of ob/ob/Cidea-/- mice was similar to that of ob/ob mice in terms of serum pa

Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis.

Adrenergic stimulation of adipocytes yields a cAMP signal that activates protein kinase A (PKA). PKA phosphorylates perilipin, a protein localized on the surface of lipid droplets that serves as a gatekeeper to regulate access of lipases converting stored triglycerides to free fatty acids and glycerol in a phosphorylation-dependent manner. Here, we report a new function for optic atrophy 1 (OPA1), a protein known to regulate mitochondrial dynamics, as a dual-specificity A-kinase anchoring protein associated with lipid droplets. By a variety of protein interaction assays, immunoprecipitation an…