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

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.

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.

The role of α-synuclein in brain lipid metabolism: a downstream impact on brain inflammatory response

2008 ◽  
Vol 326 (1-2) ◽  
pp. 55-66 ◽  
Author(s):  
Mikhail Y. Golovko ◽  
Gwendolyn Barceló-Coblijn ◽  
Paula I. Castagnet ◽  
Susan Austin ◽  
Colin K. Combs ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Inflammatory Response ◽  
Brain Lipid

scholarly journals Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
N. Auclair ◽  
N. Patey ◽  
L. Melbouci ◽  
Y. Ou ◽  
L. Magri-Tomaz ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Physiological Saline ◽  
Fatty Acid Uptake ◽  
Intimate Relationship ◽  
Acid Uptake ◽  
Acylated Ghrelin ◽  
Adipose Tissues ◽  
Syrian Golden Hamsters

AbstractAcylated ghrelin (AG) is a gastrointestinal (GI) peptide mainly secreted by the stomach that promotes cytosolic lipid droplets (CLD) hypertrophy in adipose tissues and liver. However, the role of AG in the regulation of lipid metabolism in the intestine remains unexplored. This study aimed at determining whether AG influences CLD production and chylomicron (CM) secretion in the intestine. The effects of AG and oleic acid on CLD accumulation and CM secretion were first investigated in cultured Caco-2/15 enterocytes. Intestinal lipid metabolism was also studied in Syrian Golden Hamsters submitted to conventional (CD) or Western (WD) diets for 8 weeks and continuously administered with AG or physiological saline for the ultimate 2 weeks. In cultured Caco-2/15 enterocytes, CLD accumulation influenced CM secretion while AG reduced fatty acid uptake. In WD hamsters, continuous AG treatment amplified chylomicron output while reducing postprandial CLD accumulation in the intestine. The present study supports the intimate relationship between CLD accumulation and CM secretion in the intestine and it underlines the importance of further characterizing the mechanisms through which AG exerts its effects on lipid metabolism in the intestine.

scholarly journals Embryonic cardiospecific knockout of α-E-catenin gene leads to alteration of energy metabolism in adult heart

2017 ◽  
Vol 23 (2) ◽  
pp. 65-69
Author(s):  
V. Balatskyy ◽  
L. Macewicz ◽  
O. Piven
Keyword(s):  
Lipid Metabolism ◽  
Energy Metabolism ◽  
Transgenic Mice ◽  
Lipid Droplets ◽  
Metabolic Disorders ◽  
Conditional Knockout ◽  
Heart Hypertrophy ◽  
Oil Red O Staining ◽  
Oil Red O

Previously we have shown that the α-E-catenin knockout in the embryonic heart leads to hypertrophy in adult and activation of canonical Wntsignaling. Heart hypertrophy is also accompanied by metabolic disorders, but role of the α-E-catenin in these processes is not known. Aim of our work is to study the effect of α-E-catenin deletion on the lipid metabolism in the heart. Methods. In our experiment we have used α-Е-catenin conditional knockout and αMHC-Cre transgenic mice. We have utilized histological (Oil Red O staining) and molecular biological (Western blot) methods. Results. α-Е-catenin deletion leads to accumulation of lipid droplets in myocardium, and to violation of expression and phosphorylation of key regulators of lipid metabolism (Ampk, Pparα, Acc, Hsl). Conclusions. Ous results suggest that α-Е-catenin deletion leads to inhibition of lipid metabolism in the heart.

scholarly journals Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus 

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642094582
Author(s):  
Veijo T. Salo ◽  
Maarit Hölttä-Vuori ◽  
Elina Ikonen
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Recent Work ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Intimate Relationship

Lipid droplets (LDs) are dynamic cellular hubs of lipid metabolism. While LDs contact a plethora of organelles, they have the most intimate relationship with the endoplasmic reticulum (ER). Indeed, LDs are initially assembled at specialized ER subdomains, and recent work has unraveled an increasing array of proteins regulating ER-LD contacts. Among these, seipin, a highly conserved lipodystrophy protein critical for LD growth and adipogenesis, deserves special attention. Here, we review recent insights into the role of seipin in LD biogenesis and as a regulator of ER-LD contacts. These studies have also highlighted the evolving concept of ER and LDs as a functional continuum for lipid partitioning and pinpointed a role for seipin at the ER-LD nexus in controlling lipid flux between these compartments.

Lipid droplets are dysregulated in the adult dentate gyrus during seizure

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S88-S88
Author(s):  
A Ahamad ◽  
S Ge
Keyword(s):  
Lipid Metabolism ◽  
Dentate Gyrus ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Continuous Production ◽  
Mesial Temporal Lobe Epilepsy ◽  
Inhibitory Neurons ◽  
Specific Marker ◽  
Time Points

Abstract Introduction/Objective Dentate gyrus (DG), a neurogenic niche, is a metabolically dense subregion of the hippocampus. Continuous production and integration of new neurons in the existing circuit and harmonious relationship between excitatory and inhibitory neurons accompanied by neuron-glia coupling is essential to maintain hippocampal homeostasis throughout adulthood. Imbalance in the neuronal activity generates seizures and can result in mesial temporal lobe epilepsy (MTLE). MTLE affects 50 million people across the globe and impairs the overall hippocampal network and its associated functions such as memory and cognition. Although altered lipid metabolism has been associated with status epilepticus, the role of lipid droplets (LDs), the minuscule metabolically active organelle known to provide a substrate for cellular energy, has not been explored in DG during seizure. LDs are composed of neutral lipids and surrounded by phospholipid monolayer, which is studded with a structural Perilipin family of proteins 1-5, reported to be involved in lipid metabolism. Methods/Case Report To study LDs in the brain, we used a novel approach by injecting Bodipy, a lipid dye in the tail vein of mice, and successfully labeled LDs in the DG. We used the pilocarpine-induced seizure model. After Bodipy injection followed by seizure induction, mice were sacrificed at four time-points 0.5, 1-, 3- and 18 hours. Results (if a Case Study enter NA) We found a significant increase in Bodipy signal and Perilipin 4, LDs specific marker expression at four time-points post-seizure than in the control cohort. To elucidate the role of neuron-glia metabolic coupling in DG, we measured LDs in microglia and astrocytes and found a significant increase in LDs in seizure mice than control groups suggesting the role of glia in lipid regulation in DG. Conclusion Overall, this novel study will highlight the undiscovered role of LDs in dentate gyrus during seizure and, in the future, can be used as a therapeutic target to alleviate the MTLE phenotype.

scholarly journals Impact of estrogens and estrogen receptor-α in brain lipid metabolism

2018 ◽  
Vol 315 (1) ◽  
pp. E7-E14 ◽  
Author(s):  
Eugenia Morselli ◽  
Roberta de Souza Santos ◽  
Su Gao ◽  
Yenniffer Ávalos ◽  
Alfredo Criollo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Intracellular Signaling ◽  
Fatty Acid Content ◽  
Estrogen Receptor Α ◽  
Signaling Cascades ◽  
Brain Lipid ◽  
Adipose Tissues ◽  
The Central Nervous System ◽  
The Brain

Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

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.

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