scholarly journals Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mergim Ramosaj ◽  
Sofia Madsen ◽  
Vanille Maillard ◽  
Valentina Scandella ◽  
Daniel Sudria-Lopez ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Activity ◽  
Lipid Droplets ◽  
Progenitor Cell ◽  
Adult Mouse ◽  
Cell Metabolism ◽  
Cellular Lipid ◽  
Regulatory Processes ◽  
Neural Stem Progenitor Cells

AbstractNeural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.

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 Lipids Affect the Cryptococcus neoformans-Macrophage Interaction and Promote Nonlytic Exocytosis

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Sabrina J. Nolan ◽  
Man Shun Fu ◽  
Isabelle Coppens ◽  
Arturo Casadevall
Keyword(s):  
Oleic Acid ◽  
Cryptococcus Neoformans ◽  
Lipid Droplets ◽  
Fungal Pathogens ◽  
Cellular Lipid ◽  
Content Type ◽  
Acid Supplementation

ABSTRACT Many microbes exploit host cellular lipid droplets during the host-microbe interaction, but this phenomenon has not been extensively studied for fungal pathogens. In this study, we analyzed the role of lipid droplets during the interaction of Cryptococcus neoformans with macrophages in the presence and the absence of exogenous lipids, in particular, oleate. The addition of oleic acid increased the frequency of lipid droplets in both C. neoformans and macrophages. C. neoformans responded to oleic acid supplementation by faster growth inside and outside macrophages. Fungal cells were able to harvest lipids from macrophage lipid droplets. Supplementation of C. neoformans and macrophages with oleic acid significantly increased the rate of nonlytic exocytosis while having no effect on lytic exocytosis. The process for lipid modulation of nonlytic exocytosis was associated with actin changes in macrophages. In summary, C. neoformans harvests lipids from macrophages, and the C. neoformans-macrophage interaction is modulated by exogenous lipids, providing a new tool for studying nonlytic exocytosis.

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.

Potential role of autophagy in modulation of lipid metabolism

2010 ◽  
Vol 298 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
Julia Kovsan ◽  
Nava Bashan ◽  
Andrew S. Greenberg ◽  
Assaf Rudich
Keyword(s):  
Lipid Metabolism ◽  
Protein Metabolism ◽  
Energy Production ◽  
Potential Role ◽  
Nutrient Deficiency ◽  
Energy Regulation ◽  
Cellular Lipid ◽  
Degradative Pathway ◽  
External Nutrient

Autophagy is a major degradative pathway(s) by which intracellular components are delivered into the lysosomes. It is largely implicated in determining cell death and survival because it eliminates unnecessary, damaged, and/or potentially harmful cellular products and organelles and is an important source for nutrients and energy production under conditions of external nutrient deficiency. As such, autophagy has been suggested to contribute to the regulation of carbohydrate and protein metabolism during fasting. Recently, three papers implicated a role for autophagy in cellular lipid metabolism as well. This Perspectives article presents these novel findings in the context of prior studies on the role of autophagy and lysosomes in metabolic and energy regulation, discusses their points of agreement and opposing propositions, and outlines key outstanding questions.

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 Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Duc-Vinh Pham ◽  
Pil-Hoon Park
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Binding Assay ◽  
Metabolic Reprogramming ◽  
Cellular Lipid

Abstract Background Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying molecular mechanisms for this effect are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as a crucial driver of cancer progression. Adiponectin demonstrates a wide range of metabolic activities for the modulation of lipid metabolism under physiological conditions. However, the biological actions of adiponectin in cancer-specific lipid metabolism and its role in the regulation of cancer cell growth remain elusive. Methods The effects of adiponectin on fatty acid metabolism were evaluated by measuring the cellular neutral lipid pool, free fatty acid level, and fatty acid oxidation (FAO). Colocalization between fluorescent-labeled lipid droplets and LC3/lysosomes was employed to detect lipophagy activation. Cell viability and apoptosis were examined by MTS assay, caspase-3/7 activity measurement, TUNEL assay, and Annexin V binding assay. Gene expression was determined by real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The transcriptional activity of SREBP-1 was examined by a specific dsDNA binding assay. The modulatory roles of SIRT-1 and adiponectin-activated mediators were confirmed by gene silencing and/or using their pharmacological inhibitors. Observations from in vitro assays were further validated in an MDA-MB-231 orthotopic breast tumor model. Results Globular adiponectin (gAcrp) prominently decreased the cellular lipid pool in different breast cancer cells. The cellular lipid deficiency promoted apoptosis by causing disruption of lipid rafts and blocking raft-associated signal transduction. Mechanistically, dysregulated cellular lipid homeostasis by adiponectin was induced by two concerted actions: 1) suppression of fatty acid synthesis (FAS) through downregulation of SREBP-1 and FAS-related enzymes, and 2) stimulation of lipophagy-mediated lipolysis and FAO. Notably, SIRT-1 induction critically contributed to the adiponectin-induced metabolic alterations. Finally, fatty acid metabolic remodeling by adiponectin and the key role of SIRT-1 were confirmed in nude mice bearing breast tumor xenografts. Conclusion This study elucidates the multifaceted role of adiponectin in tumor fatty acid metabolic reprogramming and provides evidence for the connection between its metabolic actions and suppression of breast cancer.

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.

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