Quantitative Lipid Analysis of Extracellular Vesicle Preparations: A Perspective

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(3)

Published: March 1, 2025

ABSTRACT Quantitative lipidomic analysis performed by mass spectrometry is required for determination of the lipid content extracellular vesicles (EVs). Such methods can provide information about total amount lipids, species composition, purity EV samples as well cellular origin EVs. There are, however, many pitfalls when performing analyses. Thus, any non‐specialist should collaborate with experts in lipidomics. In addition to good review articles giving advice analyses, we recommend and guidelines published Lipidomic Standard Initiative, an interest group affiliated International Lipidomics Society.

Language: Английский

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PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment

Published: Jan. 6, 2025

Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia debilitating loss muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, treatment regimen ignores systemic pathogenic derailments that probably dictate TB-associated mortality morbidity. Presently, it not understood whether Mtb spreads to metabolic organs brings about these impairments. Here we show creates a replication-conducive milieu lipid droplets in hepatocytes by upregulating transcription factor PPARγ scavenging lipids from host cells. In hepatocytes, shields itself against common anti-TB drugs inducing drug-metabolizing enzymes. Infection vivo aerosol mice model can be consistently observed post-week 4 along enhanced expression Moreover, histopathological analysis indeed shows presence granuloma-like structures human biopsied liver sections. Hepatotropism during chronic infectious cycle results immuno-metabolic dysregulation could magnify local pathogenicity, altering clinical presentations.

Language: Английский

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PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment

Published: Jan. 6, 2025

Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia debilitating loss muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, treatment regimen ignores systemic pathogenic derailments that probably dictate TB-associated mortality morbidity. Presently, it not understood whether Mtb spreads to metabolic organs brings about these impairments. Here we show creates a replication-conducive milieu lipid droplets in hepatocytes by upregulating transcription factor PPARγ scavenging lipids from host cells. In hepatocytes, shields itself against common anti-TB drugs inducing drug-metabolizing enzymes. Infection vivo aerosol mice model can be consistently observed post-week 4 along enhanced expression Moreover, histopathological analysis indeed shows presence granuloma-like structures human biopsied liver sections. Hepatotropism during chronic infectious cycle results immuno-metabolic dysregulation could magnify local pathogenicity, altering clinical presentations.

Language: Английский

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The Phospholipid Composition of Artificial Lipid Droplets Enhances Their Deliverability and Facilitates a Broad Biodistribution in vivo and in vitro

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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PPARγ mediated enhanced lipid biogenesis fuelsMycobacterium tuberculosisgrowth in hepatocytes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 3, 2024

Abstract Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia debilitating loss muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, treatment regimen ignores systemic pathogenic derailments that probably dictate TB-associated mortality morbidity. Presently, it not understood whether Mtb spreads to metabolic organs brings about these impairments. Here we show creates a replication-conducive milieu lipid droplets in hepatocytes by upregulating transcription factor PPARγ scavenging lipids from host cells. In hepatocytes, shields itself against common anti-TB drugs inducing drug-metabolizing enzymes. Infection vivo aerosol mice model can be consistently observed post-week 4 along enhanced expression Moreover, histopathological analysis indeed shows presence granuloma-like structures human biopsied liver sections. Hepatotropism during chronic infectious cycle results immuno-metabolic dysregulation could magnify local pathogenicity, altering clinical presentations.

Language: Английский

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α-Synuclein acts as a cholesteryl-ester sensor on lipid droplets regulating organelle size and abundance.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 20, 2024

Abstract While aggregated alpha-Synuclein (αSyn) is commonly associated with Parkinson’s disease, its physiological function as a membrane-binding protein poorly understood. Here, we show that endogenous αSyn binds lipid droplets (LDs) in multiple human cell lines and stem cell-derived dopaminergic neurons. LD-binding encompasses residues 1-100, which masks their detection by immunofluorescence microscopy, probably explaining the scarcity of similar observations earlier studies. αSyn-LD interactions are highly temperature-sensitive selective for cholesteryl-ester-rich LDs. They promote formation multimers dissociate from LDs at non-permissive temperatures. remains LD-bound throughout starvation-induced lipolysis, whereas siRNA-knockdown diminishes LD abundance compromises viability upon nutrient depletion, without affecting biosynthesis. Reciprocally, excess stimulates accumulation dependence availability, restricts organelle size ensures intracellular organization, strictly depends on functional membrane-binding. Supporting general role cellular cholesterol metabolism, our results point to additional loss-of-function similarities between Parkinson’s, Alzheimer’s Gaucher’s disease.

Language: Английский

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Novel Imidazopyridine and Imidazopyridazine Derivatives as DGAT2 Inhibitors for Treating Multiple Diseases

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(8), P. 1180 - 1181

Published: July 3, 2024

Provided herein are novel imidazopyridine and imidazopyridazine derivatives as DGAT2 inhibitors, pharmaceutical compositions, use of such compounds in treating multiple diseases, processes for preparing compounds.

Language: Английский

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Novel Triazolopyridine Derivatives as DGAT2 Inhibitors for Treating Multiple Diseases

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(9), P. 1435 - 1436

Published: Aug. 21, 2024

Provided herein are novel triazolopyridine derivatives as DGAT2 inhibitors, pharmaceutical compositions, use of such compounds in treating multiple diseases, and processes for preparing compounds.

Language: Английский

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Lipids: Emerging Players of Microglial Biology

Glia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Lipids are small molecule immunomodulators that play critical roles in maintaining cellular health and function. Microglia, the resident immune cells of central nervous system, regulate lipid metabolism both extracellular environment within intracellular compartments through various mechanisms. For instance, glycerophospholipids fatty acids interact with protein receptors on microglial surface, such as Triggering Receptor Expressed Myeloid Cells 2, influencing functions like phagocytosis migration. Moreover, cholesterol is essential not only for survival but, along other lipids acids, crucial formation, function, accumulation droplets, which modulate activity inflammatory diseases. Other lipids, including acylcarnitines ceramides, participate signaling pathways microglia. Despite complexity lipidome, a few studies have investigated effects specific classes biology. In this review, we focus major their modulating We also discuss novel analytical techniques characterizing lipidome highlight gaps current knowledge, suggesting new directions future research

Language: Английский

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Lipid droplets in health and disease

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(10), P. 1113 - 1115

Published: May 1, 2024

Lipid droplets are ubiquitous organelles that can be formed by virtually all eukaryotic cells and fulfill central roles in lipid biology. They have a unique architecture enables them to store variable amounts of neutral lipids such as triacylglycerol sterol esters hydrophobic core compartment, which is protected from the aqueous cytosol an outer phospholipid monolayer. This monolayer houses droplet surface proteome comprises large number metabolism enzymes, mediate key steps biosynthesis turnover membrane storage [[1]]. In recent years, dysfunctions started recognized causes for disease, but underlying cell biological relationships molecular mechanisms still largely enigmatic [[2, 3]]. special issue FEBS Letters entitled "Lipid health disease" aims at providing broad view our current understanding functions physiological pathological states. Sixteen review articles highlight discoveries around life cycle, important technological advances field, insights into biology inherited acquired diseases related altered storage. endoplasmic reticulum (ER), where synthesized resident enzymes. These initially soluble within ER bilayer, eventually phase-separate higher concentrations lenses, grow addition further molecules ultimately bud [[4-6]]. Beside synthesizing proteins required biogenesis process enable control over lipidome, proteome, morphology, finally metabolic dynamics emerging organelle. A player formation conserved seipin protein. Pedro Carvalho colleagues describe mechanistic its partner [[7]]. Julia Mahamid provide overview numerous contributions electron microscopy techniques form function, ranging initial monolayer-based structures players complex [[8]]. Jennifer Sapia Stefano Vanni discuss Perspective article advancements challenges employing simulations contribute basis protein targeting [[9]]. Once formed, either acquiring ER, or fusing with other manner dependent on CIDE proteins, lipid-permeable inter-organelle bridge, reviewed detail Li Xu et al. [[10]]. When require expansion their systems during nutrient deprivation when ATP-production relies β-oxidation, consumed two alternative pathways: (a) droplet-specific autophagy termed lipophagy results degradation lysosomal lipases, (b) gradual mobilization fatty acids cytosolic lipases lipolysis. Access has tightly regulated ensure homeostasis under fluctuating conditions. human cells, members perilipin family regulating lipolysis, Alenka Čopič [[11]]. Mike Henne highlights discovery subpopulation baker's yeast carries specific set anti-lipolytic [[12]]. Xiaowen Duan David Savage Graphical Review forms lipodystrophy, non-alcoholic liver disease caused mutations involved formation, fusion, lipolysis [[13]]. Hanaa Hariri buffering excess mitigating lipotoxicity, well consequences prolonged overload [[14]]. Michele Wölk Maria Federova defining lipidome [[15]]. Antonio Barbosa Symeon Siniossoglou non-canonical synthesis pathway propose unappreciated functional relevance this remodeling [[16]]. Three contact site-based communication cellular [[17-19]]. Ludovic Enkler Anne Spang detailed bases between mitochondria mammals [[17]]. Vera Monteiro-Cardoso Francesca Giordano focus tripartite sites [[18]]. Aksel Saukko-Paavola Robin Klemm role organelle crosstalk transfer defined populations adaptation [[19]]. Arun John Peter Benoît Kornmann mass-tagging-based method tracking flux across borders living task been challenging past [[20]]. Eva Herker describes implications infectious focusing how viruses exploit genome replication virions [[21]]. Albert Pol droplet-associated perilipins, acyl-CoA synthases enabling flexibility cancer progression [[22]]. The community currently dissecting (patho-) cycle collective effort. At same time, unexpected new roles, particularly collaboration organelles, emerging, range pathologies being revealed. Exciting times clearly ahead editors hope collection may inspiration scientists addressing disease. Bohnert professor Organelle Communication Medical Faculty University Münster (Germany). She studied Molecular Medicine Albert-Ludwigs-University Freiburg (Germany), she received her PhD mitochondrial biogenesis. Her interest was sparked work postdoctoral researcher Weizmann Institute Science, Rehovot (Israel). group combines high-content screening approaches biochemistry identify unknown spatial organization metabolism, understand level. Bianca Schrul Biochemistry Saarland Biology Heidelberg (Germany) also PhD. After first appointment Göttingen Max-Planck-Institute Biophysical Chemistry (now Multidisciplinary Sciences), became postdoc Department Stanford (CA, USA). Here, discovered peroxisomes share machinery some constituents laid foundation establishing own research lab employs interdisciplinary uncover droplets, explore communicate lipid-metabolizing adapt changes.

Language: Английский

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