A031 OBESITY ALTERS PULMONARY MACROPHAGE LIPID METABOLISM AND FUNCTION DURING ASTHMA

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.

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

Cellular Physiology and Biochemistry ◽

10.1159/000494791 ◽

2018 ◽

Vol 50 (5) ◽

pp. 1726-1739 ◽

Cited By ~ 4

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.

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

10.1101/2020.05.18.100990 ◽

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.

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SECTION K – LIPID METABOLISM K1 Fatty acid structure and function

BIOS Instant Notes in Biochemistry ◽

10.4324/9780203808320-61 ◽

2011 ◽

pp. 369-372

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Structure And Function ◽

Fatty Acid Structure ◽

And Function ◽

Acid Structure

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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

Molecular Biology of the Cell ◽

10.1091/mbc.e18-10-0682 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1555-1574 ◽

Cited By ~ 2

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.

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Dietary lipids, gut microbiota and lipid metabolism

Reviews in Endocrine and Metabolic Disorders ◽

10.1007/s11154-019-09512-0 ◽

2019 ◽

Vol 20 (4) ◽

pp. 461-472 ◽

Cited By ~ 40

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

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Kelch-motif containing acyl-CoA binding proteins AtACBP4 and AtACBP5 are differentially expressed and function in floral lipid metabolism

Plant Molecular Biology ◽

10.1007/s11103-016-0557-5 ◽

2016 ◽

Vol 93 (1-2) ◽

pp. 209-225 ◽

Cited By ~ 11

Author(s):

Zi-Wei Ye ◽

Jie Xu ◽

Jianxin Shi ◽

Dabing Zhang ◽

Mee-Len Chye

Keyword(s):

Lipid Metabolism ◽

Binding Proteins ◽

Differentially Expressed ◽

And Function

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Fatty Acid Components of Ovine Erythrocyte Lipids

Australian Journal of Biological Sciences ◽

10.1071/bi9650445 ◽

1965 ◽

Vol 18 (2) ◽

pp. 445 ◽

Cited By ~ 6

Author(s):

JM Connellan ◽

CJ Masters

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Lipid Metabolism ◽

Structure Function ◽

Lipid Composition ◽

Mammalian Erythrocyte ◽

Mammalian Tissues ◽

Membrane Type ◽

And Function ◽

Erythrocyte Lipids

As part of a study of comparative lipid metabolism, the distribution of fatty acids has been investigated in a number of mammalian tissues (Horgan and Masters 1963; Masters 1964a, 1964b, 1964c; Connellan and Masters 1965), a major aim of these studies being to facilitate correlation between lipid composition and function. In this context, it is widely recognized that membranes playa fundamental role in cellular metabolism, and that lipid is an essential component of these biomembranes (Stein and Danielli 1956). The study of structure-function relationships in this situation, however, has been hindered by the difficulty of isolating specific membranes without contamination by other lipids. The mature mammalian erythrocyte possesses advantageous characteristics for this type of investigation because of the lack of sub-cellular particles, and the resultant presence of only a single membrane type (Kogl et al. 1960). As an extension of previous investigations, then, the fatty acid composi-tion of ovine erythrocytes has been determined.

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