scholarly journals Split-ends is modulating lipid droplet content in adult Drosophila glial cells and is protective against paraquat toxicity

2020 ◽  
Author(s):  
Victor Girard ◽  
Valérie Goubard ◽  
Matthieu Querenet ◽  
Laurent Seugnet ◽  
Laurent Pays ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Glial Cells ◽  
Lipid Droplets ◽  
Notch Pathway ◽  
Mrna Levels ◽  
Data Mining Approach ◽  
Paraquat Toxicity ◽  
Human Ortholog ◽  
And Storage ◽  
Adult Drosophila

ABSTRACTGlial cells are early sensors of neuronal injury and are able to store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the glial functions of Spen in the context of Parkinson’s disease (PD). Using a data mining approach, we first found that the human ortholog of spen, SPEN/SHARP belongs to the set of astrocyte-expressed genes which mRNA levels are significantly different in the substantia nigra of PD patients as compared to controls. Interestingly, the retrieved list of differentially expressed genes was enriched in genes involved in lipid metabolism. In a Drosophila model of PD, we observed that spen mutant flies were more sensitive to paraquat intoxication. Moreover, the glia-restricted knockdown of spen led to the expansion and the accumulation of lipid droplets as well as the inhibition of Notch pathway. Taken together our results show that Spen regulates lipid metabolism and storage in glial cells and by these means contribute to glia-mediated functions in the context of neurodegeneration.

scholarly journals Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage

2020 ◽  
Vol 61 (3) ◽  
pp. 422-431 ◽  
Author(s):  
Lahoucine Izem ◽  
Yan Liu ◽  
Richard E. Morton
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Full Length ◽  
Intracellular Lipid ◽  
Transfer Protein ◽  
Lipid Phenotype ◽  
Exon 9 ◽  
And Storage

Cholesteryl ester transfer protein (CETP) exists as full-length (FL) and exon 9 (E9)-deleted isoforms. The function of E9-deleted CETP is poorly understood. Here, we investigated the role of E9-deleted CETP in regulating the secretion of FL-CETP by cells and explored its possible role in intracellular lipid metabolism. CETP overexpression in cells that naturally express CETP confirmed that E9-deleted CETP is not secreted, and showed that cellular FL- and E9-deleted CETP form an isolatable complex. Coexpression of CETP isoforms lowered cellular levels of both proteins and impaired FL-CETP secretion. These effects were due to reduced synthesis of both isoforms; however, the predominate consequence of FL- and E9-deleted CETP coexpression is impaired FL-CETP synthesis. We reported previously that reducing both CETP isoforms or overexpressing FL-CETP impairs cellular triglyceride (TG) storage. To investigate this further, E9-deleted CETP was expressed in SW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETP overexpression stimulated SW872 triglyceride synthesis and increased stored TG 2-fold. Expression of E9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes the transfer of TG from ER-enriched membranes to lipid droplets. E9-deleted CETP also promoted this transfer, although less effectively, and it inhibited the transfer driven by FL-CETP. We conclude that FL- and E9-deleted CETP isoforms interact to mutually decrease their intracellular levels and impair FL-CETP secretion by reducing CETP biosynthesis. E9-deleted CETP, like FL-CETP, alters cellular TG metabolism and storage but in a contrary manner.

scholarly journals Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Victor Girard ◽  
Valérie Goubard ◽  
Matthieu Querenet ◽  
Laurent Seugnet ◽  
Laurent Pays ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Notch Signaling ◽  
Glial Cell ◽  
Glial Cells ◽  
Lipid Droplets ◽  
Rna Binding ◽  
Protective Role ◽  
Differentially Expressed ◽  
Loss Of Function ◽  
Abnormal Accumulation

AbstractGlial cells are early sensors of neuronal injury and can store lipids in lipid droplets under oxidative stress conditions. Here, we investigated the functions of the RNA-binding protein, SPEN/SHARP, in the context of Parkinson’s disease (PD). Using a data-mining approach, we found that SPEN/SHARP is one of many astrocyte-expressed genes that are significantly differentially expressed in the substantia nigra of PD patients compared with control subjects. Interestingly, the differentially expressed genes are enriched in lipid metabolism-associated genes. In a Drosophila model of PD, we observed that flies carrying a loss-of-function allele of the ortholog split-ends (spen) or with glial cell-specific, but not neuronal-specific, spen knockdown were more sensitive to paraquat intoxication, indicating a protective role for Spen in glial cells. We also found that Spen is a positive regulator of Notch signaling in adult Drosophila glial cells. Moreover, Spen was required to limit abnormal accumulation of lipid droplets in glial cells in a manner independent of its regulation of Notch signaling. Taken together, our results demonstrate that Spen regulates lipid metabolism and storage in glial cells and contributes to glial cell-mediated neuroprotection.

scholarly journals Brain lipid metabolism: the emerging role of lipid droplets in glial cells

2022 ◽  
Vol 33 (1) ◽  
pp. 86-87
Author(s):  
Francesco Petrelli ◽  
Marlen Knobloch ◽  
Francesca Amati
Keyword(s):  
Lipid Metabolism ◽  
Glial Cells ◽  
Lipid Droplets ◽  
Brain Lipid

scholarly journals Effects of Lactobacillus plantarum FZU3013-Fermented Laminaria japonica on Lipid Metabolism and Gut Microbiota in Hyperlipidaemic Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Jin-Peng Hu ◽  
Ting-Ting Zheng ◽  
Bin-Fen Zeng ◽  
Man-Ling Wu ◽  
Rui Shi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lactobacillus Plantarum ◽  
Metabolic Pathways ◽  
High Fat Diet ◽  
Lipid Droplets ◽  
Short Chain Fatty Acid ◽  
Laminaria Japonica ◽  
Mrna Levels ◽  
High Fat ◽  
Positive Effect

In this study, we explored the effect of Lactobacillus plantarum FZU3013-fermented Laminaria japonica (LPLJ) supplementation to prevent hyperlipidaemia in rats fed with a high-fat diet (HFD). The results indicate that LPLJ supplementation improved serum and hepatic biochemical indicators (p < 0.05), elevated short-chain fatty acid levels, reduced HFD-induced accumulation of lipid droplets in the liver, modulated the relative abundance of some microbial phylotypes, and reduced hyperlipidaemia in HFD-fed rats by adjusting the aminoacyl-tRNA, phenylalanine, tyrosine, and tryptophan biosynthetic pathways, as well as the phenylalanine, D-glutamine and D-glutamate, and glutathione metabolic pathways. Additionally, hepatic mRNA levels of the genes involved in lipid metabolism and bile acid homeostasis were significantly reduced by LPLJ intervention (p < 0.05). These results suggest that LPLJ has a positive effect on modulating lipid metabolism and has the potential to be a functional food that can help prevent hyperlipidaemia.

scholarly journals Circulating Levels of Pro-Neurotensin and Its Relationship with Nonalcoholic Steatohepatitis and Hepatic Lipid Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 373
Author(s):  
Beatriz Villar ◽  
Laia Bertran ◽  
Carmen Aguilar ◽  
Jessica Binetti ◽  
Salomé Martínez ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Nonalcoholic Steatohepatitis ◽  
Liver Lipid ◽  
Normal Liver ◽  
Normal Weight ◽  
Published Data ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Liver Lipid Metabolism

Recent studies suggest a link between pro-neurotensin (pro-NT) and nonalcoholic fatty liver disease (NAFLD), but the published data are conflicting. Thus, we aimed to analyze pro-NT levels in women with morbid obesity (MO) and NAFLD to investigate if this molecule is involved in NAFLD and liver lipid metabolism. Plasma levels of pro-NT were determined in 56 subjects with MO and 18 with normal weight (NW). All patients with MO were subclassified according to their liver histology into the normal liver (NL, n = 20) and NAFLD (n = 36) groups. The NAFLD group had 17 subjects with simple steatosis (SS) and 19 with nonalcoholic steatohepatitis (NASH). We used a chemiluminescence sandwich immunoassay to quantify pro-NT in plasma and RT-qPCR to evaluate the hepatic mRNA levels of several lipid metabolism-related genes. We reported that pro-NT levels were significantly higher in MO with NAFLD than in MO without NAFLD. Additionally, pro-NT levels were higher in NASH patients than in NL. The hepatic expression of lipid metabolism-related genes was found to be altered in NAFLD, as previously reported. Additionally, although pro-NT levels correlated with LDL, there was no association with the main lipid metabolism-related genes. These findings suggest that pro-NT could be related to NAFLD progression.

scholarly journals CBIO-05. LIPID METABOLIC REPROGRAMMING SENSITIZES A MOLECULARLY-DEFINED SUBSET OF GLIOBLASTOMAS TO FERROPTOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
Danielle Morrow ◽  
David Nathanson ◽  
Timothy Cloughesy ◽  
Robert Prins ◽  
Nicholas Bayley ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Metabolic Reprogramming ◽  
Membrane Phospholipids ◽  
Molecular Alterations ◽  
Lipidomic Analysis ◽  
Novel Association ◽  
Therapeutic Opportunity ◽  
Dependent Cell ◽  
Main Components

Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM samples. Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Triacylglycerides (TAGs) enriched in polyunsaturated fatty acids (PUFAs) were among the most significantly altered lipids between the two groups of GBM tumors. TAGs are the main components of lipid droplets, which sequester PUFA-TAGs away from membrane phospholipids where their peroxidation can lead to ferroptosis – a regulated from of PUFA-peroxidation dependent cell death. Accordingly, the GBM subgroup with a depletion of PUFA TAGs showed heightened sensitivity to ferroptosis. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.

scholarly journals Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 322
Author(s):  
Jae-Eun Song ◽  
Tiago C. Alves ◽  
Bernardo Stutz ◽  
Matija Šestan-Peša ◽  
Nicole Kilian ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Droplets ◽  
Mitochondrial Fission ◽  
Acid Oxidation ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
And Storage

In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.

193 Single Cell RNA-sequencing Reveals a Role of Lipid Metabolism in Muscle Satellite Cells

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 104-105
Author(s):  
Shihuan Kuang ◽  
Feng Yue ◽  
Stephanie Oprescu
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Cell Fate ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Lipid Droplets ◽  
Self Renewal ◽  
Droplet Dynamics ◽  
Single Cell Rna Sequencing

Abstract Single Cell RNA-sequencing (scRNA-seq) is a powerful technique to deconvolute gene expression of various subset of cells intermingled within a complex tissue, such as the skeletal muscle. We first used scRNA-seq to understand dynamics of cell populations and their gene expression during muscle regeneration in murine limb muscles. This leads to the identification of a subset of satellite cells (the resident stem cells of skeletal muscles) with immune gene signatures in regenerating muscles. Next, we used scRNA-seq to examine gene expression dynamics of satellite cells at various status: quiescence, activation, proliferation, differentiation and self-renewal. This analysis uncovers stage-dependent changes in expression of genes related to lipid metabolism. Further analyses lead to the discovery of previously unappreciated dynamics of lipid droplets in satellite cells; and demonstrate that the abundance of the lipid droplets in newly divided satellite daughter cells is linked to cell fate segregation into differentiation versus self-renewal. Perturbation of lipid droplet dynamics through blocking lipolysis disrupts cell fate homeostasis and impairs muscle regeneration. Finally, we show that lipid metabolism regulates the function of satellite cells through two mechanisms. On one hand, lipid metabolism functions as an energy source through fatty acid oxidation (FAO), and blockage of FAO reduces energy production that is critical for satellite cell function. On the other hand, lipid metabolism generates bioactive molecules that influence signaling transduction and gene expression. In this scenario, lipid metabolism and FAO regulate the intracellular levels of acetyl-coA and selective acetylation of PAX7, a pivotal transcriptional factor underlying function of satellite cells. These results together reveal for the first time a critical role of lipid metabolism and lipid droplet dynamics in muscle satellite cell fate determination and regenerative function; and underscore a potential role of dietary fatty acids in satellite cell-dependent muscle development, growth and regeneration.

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