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.

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.

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.

Intracellular communication between lipid droplets and peroxisomes: the Janus face of PEX19

2018 ◽  
Vol 399 (7) ◽  
pp. 741-749 ◽  
Author(s):  
Bianca Schrul ◽  
Wolfgang Schliebs
Keyword(s):  
Metabolic Pathways ◽  
Lipid Droplets ◽  
Environmental Changes ◽  
Neutral Lipids ◽  
Nutrient Supply ◽  
Metabolic Energy ◽  
Central Question ◽  
And Function ◽  
Metabolic Output

Abstract In order to adapt to environmental changes, such as nutrient availability, cells have to orchestrate multiple metabolic pathways, which are catalyzed in distinct specialized organelles. Lipid droplets (LDs) and peroxisomes are both endoplasmic reticulum (ER)-derived organelles that fulfill complementary functions in lipid metabolism: Upon nutrient supply, LDs store metabolic energy in the form of neutral lipids and, when energy is needed, supply fatty acids for oxidation in peroxisomes and mitochondria. How these organelles communicate with each other for a concerted metabolic output remains a central question. Here, we summarize recent insights into the biogenesis and function of LDs and peroxisomes with emphasis on the role of PEX19 in these processes.

scholarly journals Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Pablo Esteban Morales ◽  
Jose Luis Bucarey ◽  
Alejandra Espinosa
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Specific Cell ◽  
Muscle Lipid ◽  
Cell Compartments ◽  
Carbohydrate And Lipid Metabolism ◽  
Common Causes ◽  
Specific Lipid

Skeletal muscle is one of the main regulators of carbohydrate and lipid metabolism in our organism, and therefore, it is highly susceptible to changes in glucose and fatty acid (FA) availability. Skeletal muscle is an extremely complex tissue: its metabolic capacity depends on the type of fibers it is made up of and the level of stimulation it undergoes, such as acute or chronic contraction. Obesity is often associated with increased FA levels, which leads to the accumulation of toxic lipid intermediates, oxidative stress, and autophagy in skeletal fibers. This lipotoxicity is one of the most common causes of insulin resistance (IR). In this scenario, the “isolation” of certain lipids in specific cell compartments, through the action of the specific lipid droplet, perilipin (PLIN) family of proteins, is conceived as a lifeguard compensatory strategy. In this review, we summarize the cellular mechanism underlying lipid mobilization and metabolism inside skeletal muscle, focusing on the function of lipid droplets, the PLIN family of proteins, and how these entities are modified in exercise, obesity, and IR conditions.

scholarly journals Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Karamat Mohammad ◽  
Paméla Dakik ◽  
Younes Medkour ◽  
Mélissa McAuley ◽  
Darya Mitrofanova ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Palmitoleic Acid ◽  
Molecular Mechanisms ◽  
Neutral Lipids ◽  
Yeast Cells ◽  
Cellular Processes ◽  
Regulated Cell Death

A disturbed homeostasis of cellular lipids and the resulting lipotoxicity are considered to be key contributors to many human pathologies, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer. The yeast Saccharomyces cerevisiae has been successfully used for uncovering molecular mechanisms through which impaired lipid metabolism causes lipotoxicity and elicits different forms of regulated cell death. Here, we discuss mechanisms of the “liponecrotic” mode of regulated cell death in S. cerevisiae. This mode of regulated cell death can be initiated in response to a brief treatment of yeast with exogenous palmitoleic acid. Such treatment prompts the incorporation of exogenously added palmitoleic acid into phospholipids and neutral lipids. This orchestrates a global remodeling of lipid metabolism and transfer in the endoplasmic reticulum, mitochondria, lipid droplets, and the plasma membrane. Certain features of such remodeling play essential roles either in committing yeast to liponecrosis or in executing this mode of regulated cell death. We also outline four processes through which yeast cells actively resist liponecrosis by adapting to the cellular stress imposed by palmitoleic acid and maintaining viability. These prosurvival cellular processes are confined in the endoplasmic reticulum, lipid droplets, peroxisomes, autophagosomes, vacuoles, and the cytosol.

scholarly journals Ginsenoside Rg3 Induces Browning of 3T3-L1 Adipocytes by Activating AMPK Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 427 ◽  
Author(s):  
Kyungtae Kim ◽  
Ki Hong Nam ◽  
Sang Ah Yi ◽  
Jong Woo Park ◽  
Jeung-Whan Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Panax Ginseng ◽  
Lipid Droplets ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Ginsenoside Rg3 ◽  
White Adipocytes

Ginsenoside Rg3, one of the major components in Panax ginseng, has been reported to possess several therapeutic effects including anti-obesity properties. However, its effect on the browning of mature white adipocytes as well as the underlying mechanism remains poorly understood. In this study, we suggested a novel role of Rg3 in the browning of mature 3T3-L1 adipocytes by upregulating browning-related gene expression. The browning effects of Rg3 on differentiated 3T3-L1 adipocytes were evaluated by analyzing browning-related markers using quantitative PCR, immunoblotting, and immunostaining. In addition, the size and sum area of lipid droplets in differentiated 3T3-L1 adipocytes were measured using Oil-Red-O staining. In mature 3T3-L1 adipocytes, Rg3 dose-dependently induced the expression of browning-related genes such as Ucp1, Prdm16, Pgc1α, Cidea, and Dio2. Moreover, Rg3 induced the expression of beige fat-specific genes (CD137 and TMEM26) and lipid metabolism-associated genes (FASN, SREBP1, and MCAD), which indicated the activation of lipid metabolism by Rg3. We also demonstrated that activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) is required for Rg3-mediated up-regulation of browning gene expression. Moreover, Rg3 inhibited the accumulation of lipid droplets and reduced the droplet size in mature 3T3-L1 adipocytes. Taken together, this study identifies a novel role of Rg3 in browning of white adipocytes, as well as suggesting a potential mechanism of an anti-obesity effect of Panax ginseng.

scholarly journals Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis

2020 ◽  
Vol 3 (6) ◽  
pp. e202000715
Author(s):  
Nimesha Tadepalle ◽  
Lennart Robers ◽  
Matteo Veronese ◽  
Peter Zentis ◽  
Felix Babatz ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Plastic Behavior ◽  
Glucose Starvation ◽  
Spastic Paraplegia ◽  
Microtubule Severing ◽  
Tag Accumulation

Lipid droplets (LDs) are metabolic organelles that store neutral lipids and dynamically respond to changes in energy availability by accumulating or mobilizing triacylglycerols (TAGs). How the plastic behavior of LDs is regulated is poorly understood. Hereditary spastic paraplegia is a central motor axonopathy predominantly caused by mutations in SPAST, encoding the microtubule-severing protein spastin. The spastin-M1 isoform localizes to nascent LDs in mammalian cells; however, the mechanistic significance of this targeting is not fully explained. Here, we show that tightly controlled levels of spastin-M1 are required to inhibit LD biogenesis and TAG accumulation. Spastin-M1 maintains the morphogenesis of the ER when TAG synthesis is prevented, independent from microtubule binding. Moreover, spastin plays a microtubule-dependent role in mediating the dispersion of LDs from the ER upon glucose starvation. Our results reveal a dual role of spastin to shape ER tubules and to regulate LD movement along microtubules, opening new perspectives for the pathogenesis of hereditary spastic paraplegia.

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