scholarly journals Genetic Ablation of Calcium-independent Phospholipase A2γ Leads to Alterations in Mitochondrial Lipid Metabolism and Function Resulting in a Deficient Mitochondrial Bioenergetic Phenotype

2007 ◽  
Vol 282 (48) ◽  
pp. 34611-34622 ◽  
Author(s):  
David J. Mancuso ◽  
Harold F. Sims ◽  
Xianlin Han ◽  
Christopher M. Jenkins ◽  
Shao Ping Guan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Genetic Ablation ◽  
Mitochondrial Lipid ◽  
And Function

scholarly journals Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

2018 ◽  
Vol 50 (5) ◽  
pp. 1726-1739 ◽  
Author(s):  
Jing Tian ◽  
Wenzhu Tang ◽  
Ming Xu ◽  
Chen Zhang ◽  
Pei Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Leptin Receptor ◽  
Myocardial Hypertrophy ◽  
Oxphos Complex ◽  
H9c2 Cardiomyocytes ◽  
Mitochondrial Lipid ◽  
And Function ◽  
Shengmai San

Background/Aims: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. Methods: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR. Results: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes. Conclusion: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism.

scholarly journals Impact of obesity and SARS-CoV-2 infection: implications for host defence - a living review

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Felix Clemens Richter ◽  
Aljawharah Alrubayyi ◽  
Alicia Teijeira Crespo ◽  
Sarah Hulin-Curtis ◽  
Keyword(s):  
Lipid Metabolism ◽  
Influenza A ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Low Grade ◽  
Obese Patients ◽  
Healthy Weight ◽  
Virus Infections ◽  
Immune Alterations ◽  
And Function

Abstract The role of obesity in the pathophysiology of respiratory virus infections has become particularly apparent during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, where obese patients are twice as likely to suffer from severe coronavirus disease 2019 (COVID-19) than healthy weight individuals. Obesity results in disruption of systemic lipid metabolism promoting a state of chronic low-grade inflammation. However, it remains unclear how these underlying metabolic and cellular processes promote severe SARS-CoV-2 infection. Emerging data in SARS-CoV-2 and Influenza A virus (IAV) infections show that viruses can further subvert the host’s altered lipid metabolism and exploit obesity-induced alterations in immune cell metabolism and function to promote chronic inflammation and viral propagation. In this review, we outline the systemic metabolic and immune alterations underlying obesity and discuss how these baseline alterations impact the immune response and disease pathophysiology. A better understanding of the immunometabolic landscape of obese patients may aid better therapies and future vaccine design.

scholarly journals Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila

2020 ◽  
Author(s):  
Qian Dong ◽  
Michael Zavortink ◽  
Francesca Froldi ◽  
Sofya Golenkina ◽  
Tammy Lam ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cell Cycle Progression ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Post Translational Modification ◽  
Final Size ◽  
Neural Lineage ◽  
Signalling Molecule ◽  
Lipid Metabolism Genes ◽  
And Function

AbstractThe final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.

scholarly journals p38δ genetic ablation protects female mice from anthracycline cardiotoxicity

2020 ◽  
Author(s):  
Sharon A George ◽  
Alexi Kiss ◽  
Sofian N Obaid ◽  
Aileen Venegas ◽  
Trisha Talapatra ◽  
...  
Keyword(s):  
Cardiac Injury ◽  
Mapk Signaling ◽  
Anthracycline Cardiotoxicity ◽  
Genetic Ablation ◽  
Female Mice ◽  
Echocardiographic Parameters ◽  
The Individual ◽  
And Function ◽  
First Time ◽  
Dose Dependent

ABSTRACTBACKGROUNDThe efficacy of an anthracycline antibiotic doxorubicin (DOX) as a chemotherapeutic agent is limited by dose-dependent cardiotoxicity. DOX is associated with activation of intracellular stress signaling pathways including p38 MAPKs. While previous studies have implicated p38 MAPK signaling in DOX-induced cardiac injury, the roles of the individual p38 isoforms, specifically, of the alternative isoforms p38γ and p38δ, remain uncharacterized.OBJECTIVESTo determine the potential cardioprotective effects of p38γ and p38δ genetic deletion in mice subjected to acute DOX treatment.METHODSMale and female wild-type (WT), p38γ-/-, p38δ-/- and p38γ-/-δ-/- mice were injected with 30 mg/kg DOX and their survival was tracked for ten days. During this period cardiac function was assessed by echocardiography and electrocardiography and fibrosis by PicroSirius Red staining. Immunoblotting was performed to assess the expression of signaling proteins and markers linked to autophagy.RESULTSSignificantly improved survival was observed in p38δ-/- female mice post-DOX relative to WT females, but not in p38γ-/- or p38γ-/-δ-/- male or female mice. The improved survival in DOX-treated p38δ-/- females was associated with decreased fibrosis, increased cardiac output and LV diameter relative to DOX-treated WT females, and similar to saline-treated controls. Structural and echocardiographic parameters were either unchanged or worsened in all other groups. Increased autophagy, as evidenced by increased LC3-II level, and decreased mTOR activation was also observed in DOX-treated p38δ-/- females.CONCLUSIONSp38δ plays a crucial role in promoting DOX-induced cardiotoxicity in female mice by inhibiting autophagy. Therefore, p38δ targeting could be a potential cardioprotective strategy in anthracycline chemotherapy.NEW AND NOTEWORTHYThis study for the first time identifies the roles of the alternative p38γ and p38δ MAPK isoforms in promoting DOX-cardiotoxicity in a sex-specific manner. While p38γ systemic deletion did not affect DOX-cardiotoxicity, p38δ systemic deletion was cardioprotective in female but not in male mice. Cardiac structure and function were preserved in DOX-treated p38δ-/- females and autophagy was increased.

scholarly journals Analysis of the roles of phosphatidylinositol-4,5-bisphosphate and individual subunits in assembly, localization, and function of Saccharomyces cerevisiae target of rapamycin complex 2

2019 ◽  
Vol 30 (12) ◽  
pp. 1555-1574 ◽  
Author(s):  
Maria Nieves Martinez Marshall ◽  
Anita Emmerstorfer-Augustin ◽  
Kristin L. Leskoske ◽  
Lydia H. Zhang ◽  
Biyun Li ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Lipid Metabolism ◽  
Eukaryotic Cell ◽  
Target Of Rapamycin ◽  
Multiprotein Complex ◽  
Ph Domain ◽  
Evolutionarily Conserved ◽  
And Function

Eukaryotic cell survival requires maintenance of plasma membrane (PM) homeostasis in response to environmental insults and changes in lipid metabolism. In yeast, a key regulator of PM homeostasis is target of rapamycin (TOR) complex 2 (TORC2), a multiprotein complex containing the evolutionarily conserved TOR protein kinase isoform Tor2. PM localization is essential for TORC2 function. One core TORC2 subunit (Avo1) and two TORC2-­associated regulators (Slm1 and Slm2) contain pleckstrin homology (PH) domains that exhibit specificity for binding phosphatidylinositol-4,5- bisphosphate (PtdIns4,5P2). To investigate the roles of PtdIns4,5P2 and constituent subunits of TORC2, we used auxin-inducible degradation to systematically eliminate these factors and then examined localization, association, and function of the remaining TORC2 components. We found that PtdIns4,5P2 depletion significantly reduced TORC2 activity, yet did not prevent PM localization or cause disassembly of TORC2. Moreover, truncated Avo1 (lacking its C-terminal PH domain) was still recruited to the PM and supported growth. Even when all three PH-containing proteins were absent, the remaining TORC2 subunits were PM-bound. Revealingly, Avo3 localized to the PM independent of both Avo1 and Tor2, whereas both Tor2 and Avo1 required Avo3 for their PM anchoring. Our findings provide new mechanistic information about TORC2 and pinpoint Avo3 as pivotal for TORC2 PM localization and assembly in vivo.

scholarly journals Dietary lipids, gut microbiota and lipid metabolism

2019 ◽  
Vol 20 (4) ◽  
pp. 461-472 ◽  
Author(s):  
Marc Schoeler ◽  
Robert Caesar
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Dietary Lipids ◽  
Lipid Levels ◽  
And Function ◽  
Host Metabolism ◽  
Secondary Bile Acids

Abstract The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet properties such as the amount and composition of lipids. Hence, dietary lipids may influence host physiology through interaction with the gut microbiota. Lipids affect the gut microbiota both as substrates for bacterial metabolic processes, and by inhibiting bacterial growth by toxic influence. The gut microbiota has been shown to affect lipid metabolism and lipid levels in blood and tissues, both in mice and humans. Furthermore, diseases linked to dyslipidemia, such as non-alcoholic liver disease and atherosclerosis, are associated with changes in gut microbiota profile. The influence of the gut microbiota on host lipid metabolism may be mediated through metabolites produced by the gut microbiota such as short-chain fatty acids, secondary bile acids and trimethylamine and by pro-inflammatory bacterially derived factors such as lipopolysaccharide. Here we will review the association between gut microbiota, dietary lipids and lipid metabolism

scholarly journals The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease

2008 ◽  
Vol 205 (9) ◽  
pp. 2005-2017 ◽  
Author(s):  
Mark M.W. Chong ◽  
Jeffrey P. Rasmussen ◽  
Alexander Y. Rudensky ◽  
Dan R. Littman
Keyword(s):  
T Cell ◽  
Inflammatory Disease ◽  
Cell Types ◽  
Mirna Biogenesis ◽  
Cell Compartment ◽  
Foxp3 Gene ◽  
Genetic Ablation ◽  
And Function ◽  
Specific Deletion

MicroRNAs (miRNAs) are implicated in the differentiation and function of many cell types. We provide genetic and in vivo evidence that the two RNaseIII enzymes, Drosha and Dicer, do indeed function in the same pathway. These have previously been shown to mediate the stepwise maturation of miRNAs (Lee, Y., C. Ahn, J. Han, H. Choi, J. Kim, J. Yim, J. Lee, P. Provost, O. Radmark, S. Kim, and V.N. Kim. 2003. Nature. 425:415–419), and genetic ablation of either within the T cell compartment, or specifically within Foxp3+ regulatory T (T reg) cells, results in identical phenotypes. We found that miRNA biogenesis is indispensable for the function of T reg cells. Specific deletion of either Drosha or Dicer phenocopies mice lacking a functional Foxp3 gene or Foxp3+ cells, whereas deletion throughout the T cell compartment also results in spontaneous inflammatory disease, but later in life. Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity.

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