scholarly journals An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

Cell Reports ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 44-55 ◽  
Author(s):  
Daniel F. Markgraf ◽  
Robin W. Klemm ◽  
Mirco Junker ◽  
Hans K. Hannibal-Bach ◽  
Christer S. Ejsing ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Neutral Lipid ◽  
Lipid Droplets ◽  
Lipid Synthesis ◽  
Membrane Lipid

scholarly journals Circadian Gene PER2 Silencing Downregulates PPARG and SREBF1 and Suppresses Lipid Synthesis in Bovine Mammary Epithelial Cells

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1226
Author(s):  
Yujia Jing ◽  
Yifei Chen ◽  
Shan Wang ◽  
Jialiang Ouyang ◽  
Liangyu Hu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Epithelial Cells ◽  
Circadian Clock ◽  
Lipid Droplets ◽  
Mammary Epithelial Cells ◽  
Lipid Synthesis ◽  
Mammary Epithelial ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bovine Mammary Epithelial Cells

PER2, a circadian clock gene, is associated with mammary gland development and lipid synthesis in rodents, partly via regulating peroxisome proliferator-activated receptor gamma (PPARG). Whether such a type of molecular link existed in bovines was unclear. We hypothesized that PER2 was associated with lipid metabolism and regulated cell cycles and apoptosis in bovine mammary epithelial cells (BMECs). To test this hypothesis, BMECs isolated from three mid-lactation (average 110 d postpartum) cows were used. The transient transfection of small interfering RNA (siRNA) was used to inhibit PER2 transcription in primary BMECs. The silencing of PER2 led to lower concentrations of cellular lipid droplets and triacylglycerol along with the downregulation of lipogenic-related genes such as ACACA, FASN, LPIN1, and SCD, suggesting an overall inhibition of lipogenesis and desaturation. The downregulation of PPARG and SREBF1 in response to PER2 silencing underscored the importance of circadian clock signaling and the transcriptional regulation of lipogenesis. Although the proliferation of BMECs was not influenced by PER2 silencing, the number of cells in the G2/GM phase was upregulated. PER2 silencing did not affect cell apoptosis. Overall, the data provided evidence that PER2 participated in the coordination of mammary lipid metabolism and was potentially a component of the control of lipid droplets and TAG synthesis in ruminant mammary cells. The present data suggested that such an effect could occur through direct effects on transcriptional regulators.

scholarly journals Lipid synthesis in human erythroid cells: the effect of sickling

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 189-195 ◽  
Author(s):  
TA Lane ◽  
SK Ballas ◽  
ER Burka
Keyword(s):  
Cell Membrane ◽  
Neutral Lipid ◽  
Sickle Cell Anemia ◽  
De Novo ◽  
Membrane Lipids ◽  
Membrane Damage ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Erythroid Cell ◽  
Cell Membrane Damage

Abstract Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.

scholarly journals Whole Lotta Lipids—From HCV RNA Replication to the Mature Viral Particle

2020 ◽  
Vol 21 (8) ◽  
pp. 2888 ◽  
Author(s):  
Hanna Bley ◽  
Anja Schöbel ◽  
Eva Herker
Keyword(s):  
Lipid Droplets ◽  
Fatty Acid Content ◽  
Lipid Synthesis ◽  
Rna Replication ◽  
Membrane Lipid ◽  
Hcv Rna ◽  
The Past ◽  
Lipoprotein Association ◽  
Key Pathways

Replication of the hepatitis C virus (HCV) strongly relies on various lipid metabolic processes in different steps of the viral life cycle. In general, HCV changes the cells’ lipidomic profile by differentially regulating key pathways of lipid synthesis, remodeling, and utilization. In this review, we sum up the latest data mainly from the past five years, emphasizing the role of lipids in HCV RNA replication, assembly, and egress. In detail, we highlight changes in the fatty acid content as well as alterations of the membrane lipid composition during replication vesicle formation. We address the role of lipid droplets as a lipid provider during replication and as an essential hub for HCV assembly. Finally, we depict different ideas of HCV maturation and egress including lipoprotein association and potential secretory routes.

scholarly journals The p97-UBXD8 complex modulates ER-Mitochondria contact sites by modulating membrane lipid saturation and composition

2021 ◽  
Author(s):  
Rakesh Ganji ◽  
Joao A. Paulo ◽  
Yuecheng Xi ◽  
Ian Kline ◽  
Jiang Zhu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Composition ◽  
Unsaturated Fatty Acids ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Loss Of Function ◽  
Membrane Lipid Composition ◽  
Aaa Atpase ◽  
Contact Sites ◽  
Lipid Species

AbstractThe intimate association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-mitochondria contact sites serves as a platform for several critical cellular processes, in particular lipid synthesis. Enzymes involved in lipid biosynthesis are enriched at contacts and membrane lipid composition at contacts is distinct relative to surrounding membranes. How contacts are remodeled and the subsequent biological consequences of altered contacts such as perturbed lipid metabolism remains poorly understood. Here we show that the p97 AAA-ATPase and its ER-tethered ubiquitin-X domain adaptor 8 (UBXD8) regulate the prevalence of ER-mitochondria contacts. The p97-UBXD8 complex localizes to contacts and loss of this complex increases contacts in a manner that is dependent on p97 catalytic activity. Quantitative proteomics of purified contacts demonstrates alterations in proteins regulating lipid metabolism upon loss of UBXD8. Furthermore, lipidomics studies indicate significant changes in distinct lipid species in UBXD8 knockout cells. We show that loss of p97-UBXD8 results in perturbed contacts due to an increase in membrane lipid saturation via SREBP1 and the lipid desaturase SCD1. Aberrant contacts in p97-UBXD8 loss of function cells can be rescued by supplementation with unsaturated fatty acids or overexpression of SCD1. Perturbation of contacts and inherent lipid synthesis is emerging as a hallmark to a variety of human disorders such as neurodegeneration. Notably, we find that the SREBP1-SCD1 pathway is negatively impacted in the brains of mice with p97 mutations that cause neurodegeneration. Our results suggest that contacts are exquisitely sensitive to alterations to membrane lipid composition and saturation in a manner that is dependent on p97-UBXD8.

scholarly journals Lipid synthesis in human erythroid cells: the effect of sickling

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 189-195
Author(s):  
TA Lane ◽  
SK Ballas ◽  
ER Burka
Keyword(s):  
Cell Membrane ◽  
Neutral Lipid ◽  
Sickle Cell Anemia ◽  
De Novo ◽  
Membrane Lipids ◽  
Membrane Damage ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Erythroid Cell ◽  
Cell Membrane Damage

Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.

scholarly journals The inflammatory accumulation of lipids and ROS in human Nrf1α-deficient hepatoma cells is ameliorated by 2-bromopalmitate

2021 ◽  
Author(s):  
Ze Zheng ◽  
Meng Wang ◽  
Shaofan Hu ◽  
Rongzhen Deng ◽  
Jing Feng ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
Lipid Synthesis ◽  
Hepatoma Cells ◽  
Wild Type ◽  
Uptake Capacity ◽  
Potential Strategy ◽  
Decomposition Pathway ◽  
Accumulation Of Lipids

Abstract: Since Nrf1 and Nrf2 are essential for regulating the lipid metabolism pathways, their dysregulation was also shown to be critically involved in the non-controllable inflammatory pathology into cancer development. However, it is unknown that the interaction between Nrf1 and Nrf2 in the regulation of lipid metabolism, especially in hepatoma cells. Here, we have further explored the molecular mechanisms underlying their distinct regulation of lipid metabolism, by comparative analysis of changes in those lipid metabolism-related genes in Nrf1α-/- and/or Nrf2-/- cell lines relative to wild-type controls. The results revealed that loss of Nrf1 leads to disordered lipid metabolism; its lipid synthesis pathway was up-regulated by JNK-Nrf2-AP1 signaling, while its lipid decomposition pathway was down-regulated by the nuclear receptor PPAR-PGC1 signaling, resulting in severe accumulation of lipids as deposited in lipid droplets. By contrast, knockout of Nrf2 gave rise to decreases in lipid synthesis and uptake capacity. These demonstrate that Nrf1 and Nrf2 contribute to significant differences in the cellular lipid metabolism regulatory profiles and relevant pathological responses. Further experiments unraveled that lipid deposition in Nrf1α-/- cells was resulted from CD36 upregulation by activating the PI3K-AKT-mTOR pathway, leading to induction of the inflammatory response. Following treatment of Nrf1[alpha]-/- cells with 2-bromopalmitate (2BP), it enabled the yield of lipid droplets to be strikingly alleviated, as companied by substantial abolishment of CD36 and critical inflammatory cytokines. Such Nrf1[alpha]-/--led inflammatory accumulation of lipids and ROS was significantly ameliorated by 2BP. Overall, this study provides a potential strategy for cancer prevention and treatment by precision targeting of Nrf1, Nrf2, or both.

scholarly journals Triple-Knockout, Synuclein-Free Mice Display Compromised Lipid Pattern

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3078
Author(s):  
Irina A. Guschina ◽  
Natalia Ninkina ◽  
Andrei Roman ◽  
Mikhail V. Pokrovskiy ◽  
Vladimir L. Buchman
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Family Members ◽  
Ether Lipid ◽  
Brain Regions ◽  
Membrane Lipid ◽  
Lipid Binding ◽  
Synaptic Functions ◽  
Ethanolamine Plasmalogens ◽  
Lipid Pattern

Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. These are among aspects of decreased synuclein functions that are still poorly acknowledged especially in regard to pathogenesis in Parkinson’s disease. Here, we aimed to add to existing knowledge of synuclein deficiency (i.e., the lack of all three family members), with respect to changes in fatty acids and lipids in plasma, liver, and two brain regions in triple synuclein-knockout (TKO) mice. We describe changes of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and non-esterified fatty acids in plasma of synuclein free mice. In midbrain, we observed counterbalanced changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER). We also recorded a notable reduction in ethanolamine plasmalogens in the midbrain of synuclein free mice, which is an important finding since the abnormal ether lipid metabolism usually associated with neurological disorders. In summary, our data demonstrates that synuclein deficiency results in alterations of the PUFA synthesis, storage lipid accumulation in the liver, and the reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members causes more profound changes in lipid metabolism than changes previously shown to be associated with γ-synuclein deficiency alone. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

scholarly journals Lipid Remodeling Confers Osmotic Stress Tolerance to Embryogenic Cells during Cryopreservation

2021 ◽  
Vol 22 (4) ◽  
pp. 2174
Author(s):  
Liang Lin ◽  
Junchao Ma ◽  
Qin Ai ◽  
Hugh W. Pritchard ◽  
Weiqi Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Technology Development ◽  
Membrane Lipids ◽  
Species Conservation ◽  
Membrane Lipid ◽  
Cell Integrity ◽  
Embryogenic Cells ◽  
Osmotic Stress Tolerance ◽  
Lipid Species ◽  
Magnolia Officinalis

Plant species conservation through cryopreservation using plant vitrification solutions (PVS) is based in empiricism and the mechanisms that confer cell integrity are not well understood. Using ESI-MS/MS analysis and quantification, we generated 12 comparative lipidomics datasets for membranes of embryogenic cells (ECs) of Magnolia officinalis during cryogenic treatments. Each step of the complex PVS-based cryoprotocol had a profoundly different impact on membrane lipid composition. Loading treatment (osmoprotection) remodeled the cell membrane by lipid turnover, between increased phosphatidic acid (PA) and phosphatidylglycerol (PG) and decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PA increase likely serves as an intermediate for adjustments in lipid metabolism to desiccation stress. Following PVS treatment, lipid levels increased, including PC and PE, and this effectively counteracted the potential for massive loss of lipid species when cryopreservation was implemented in the absence of cryoprotection. The present detailed cryobiotechnology findings suggest that the remodeling of membrane lipids and attenuation of lipid degradation are critical for the successful use of PVS. As lipid metabolism and composition varies with species, these new insights provide a framework for technology development for the preservation of other species at increasing risk of extinction.

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.

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