scholarly journals Epilipidomics platform for holistic profiling of oxidized complex lipids in blood plasma of obese individuals

2021 ◽  
Author(s):  
Angela Criscuolo ◽  
Palina Nepachalovich ◽  
Diego Fernando Garcia-del Rio ◽  
Mike Lange ◽  
Zhixu Ni ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Metabolic Disorders ◽  
Neutral Lipids ◽  
Structural Diversity ◽  
Oxidized Lipids ◽  
Lipid Modifications ◽  
Specific Manner ◽  
Acyl Chains ◽  
Complex Lipids ◽  
Regulatory Significance

Lipids are a structurally diverse class of biomolecules which can undergo a variety of chemical modifications. Among them, lipid (per)oxidation attracts most of the attention due to its significance in regulation of inflammation, cell proliferation and death programs. Despite their apparent regulatory significance, the molecular repertoire of oxidized lipids remains largely elusive as accurate annotation of lipid modifications is challenged by their low abundance and largely unknown, biological context-dependent structural diversity. Here we provide a holistic workflow based on the combination of bioinformatics and LC-MS/MS technologies to support identification and relative quantification of oxidized complex lipids in a modification type- and position-specific manner. The developed methodology was used to identify epilipidomics signatures of lean and obese individuals with and without type II diabetes. Characteristic signature of lipid modifications in lean individuals, dominated by the presence of modified octadecanoid acyl chains in phospho- and neutral lipids, was drastically shifted towards lipid peroxidation-driven accumulation of oxidized eicosanoids, suggesting significant alteration of endocrine signalling by oxidized lipids in metabolic disorders.

scholarly journals Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander Beatty ◽  
Tanu Singh ◽  
Yulia Y. Tyurina ◽  
Vladimir A. Tyurin ◽  
Svetlana Samovich ◽  
...  
Keyword(s):  
Cell Death ◽  
Therapeutic Potential ◽  
Neutral Lipids ◽  
Cell Types ◽  
Lipid Hydroperoxides ◽  
Conjugated Linolenic Acids ◽  
Cellular Lipids ◽  
Transcriptional Changes ◽  
Acyl Chains ◽  
Tumor Growth And Metastasis

AbstractFerroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.

scholarly journals Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation

2019 ◽  
Vol 20 (7) ◽  
pp. 1660 ◽  
Author(s):  
Alicia Bort ◽  
Belén Sánchez ◽  
Pedro Mateos-Gómez ◽  
Inés Díaz-Laviada ◽  
Nieves Rodríguez-Henche
Keyword(s):  
Hepg2 Cells ◽  
Metabolic Disorders ◽  
Dietary Habits ◽  
Neutral Lipids ◽  
Hepatic Lipogenesis ◽  
Diet Induced Obesity ◽  
Primary Health ◽  
Neutral Lipid Content ◽  
Chili Peppers

Obesity, a major risk factor for chronic diseases such as type 2 diabetes (T2D), represents a serious primary health problem worldwide. Dietary habits are of special interest to prevent and counteract the obesity and its associated metabolic disorders, including lipid steatosis. Capsaicin, a pungent compound of chili peppers, has been found to ameliorate diet-induced obesity in rodents and humans. The purpose of this study was to examine the effect of capsaicin on hepatic lipogenesis and to delineate the underlying signaling pathways involved, using HepG2 cells as an experimental model. Cellular neutral lipids, stained with BODIPY493/503, were quantified by flow cytometry, and the protein expression and activity were determined by immunoblotting. Capsaicin reduced basal neutral lipid content in HepG2 cells, as well that induced by troglitazone or by oleic acid. This effect of capsaicin was prevented by dorsomorphin and GW9662, pharmacological inhibitors of AMPK and PPARγ, respectively. In addition, capsaicin activated AMPK and inhibited the AKT/mTOR pathway, major regulators of hepatic lipogenesis. Furthermore, capsaicin blocked autophagy and increased PGC-1α protein. These results suggest that capsaicin behaves as an anti-lipogenic compound in HepG2 cells.

The possible role of Saponin in Type-II Diabetes- A review

2020 ◽  
Vol 16 ◽  
Author(s):  
Neeraj Choudhary ◽  
Gopal Lal Khatik ◽  
Ashish Suttee
Keyword(s):  
Secondary Metabolites ◽  
Type Ii Diabetes ◽  
Structural Diversity ◽  
Complete Information ◽  
Current Data ◽  
Type Ii ◽  
Glucose Levels ◽  
Therapeutic Benefits ◽  
The Impact

Background: The possible role of secondary metabolites in the management of diabetes is a great concern and constant discussion. This characteristic seems relevant and should be the subject of thorough discussion with respect to saponin. Objective: Current data mainly focus on the impact of saponin in the treatment of type-II diabetes. The majority of studies emphasis on other secondary metabolites such as alkaloids and flavonoids but very few papers are there representing the possible role of saponin as these papers express the narrow perspective of saponin phytoconstituents but lacking in providing the complete information on various saponin plants. The aim of the study was to summarize all available data concerning the saponin containing plant in the management of type-II diabetes. Methods: All relevant papers on saponin were selected. This review summarizes the saponins isolation method, mechanism of action, clinical significance, medicinal plants and phytoconstituents responsible for producing a therapeutic effect in the management of diabetes. Results: The saponin is of high potential with structural diversity and inhibits diabetic complications along with reducing the hyperglycemia through different mechanisms thereby providing scope for improving the existing therapy and developing the novel medicinal agents for curing diabetes. Conclusion: Saponins having potential therapeutic benefits and are theorized as an alternative medication in decreasing serum blood glucose levels in the patient suffering from diabetes.

Neutral Lipids Rigidify Unsaturated Acyl Chains in Senescing Membranes

1983 ◽  
Vol 34 (3) ◽  
pp. 268-276 ◽  
Author(s):  
R. F. BARBER ◽  
J. E. THOMPSON
Keyword(s):  
Neutral Lipids ◽  
Unsaturated Acyl ◽  
Acyl Chains

Evaluation of possible mechanisms of phorbol ester stimulation of phosphatidylcholine synthesis in HeLa cells

1985 ◽  
Vol 63 (2) ◽  
pp. 145-151 ◽  
Author(s):  
H. W. Cook ◽  
D. E. Vance
Keyword(s):  
Fatty Acids ◽  
Phorbol Ester ◽  
Hela Cells ◽  
Phorbol Esters ◽  
Neutral Lipids ◽  
Cellular Fatty Acid ◽  
Fatty Acyl ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Intracellular Release ◽  
Acyl Chains

Phorbol esters, including 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12,13-dibutyrylphorbol acetate, markedly stimulate the synthesis of phosphatidylcholine (PC) and the activity of CTP:phosphocholine cytidylyltransferase (CT) in cultured HeLa cells. Two possible mechanisms whereby the phorbol esters stimulated PC biosynthesis were investigated. One consideration was that phorbol esters may induce the release of fatty acyl chains from endogenous complex lipids; increased fatty acids or fatty acyl-CoAs could cause the translocation of CT from cytosol to microsomes and thereby increase the activity of the rate-limiting enzyme in PC synthesis. In HeLa cells prelabeled with [3H]oleate or [3H]arachidonate, phorbol ester treatment increased the redistribution of arachidonate in phospholipids and neutral lipids and release of label to the medium, but there was little effect on the cellular fatty acid pools with either of the labeled fatty acids or of the phorbol esters. A second possibility was that protein kinase C (PKC), a receptor for phorbol esters, might be involved in activation of CT activity. TPA stimulated the phosphorylation of cytosolic proteins of HeLa cells more than twofold during a 10- or 60-min incubation with 32Pi. However, an approximate sixfold purified preparation of PKC from rat brain did not stimulate the activity of partially purified (12- to 15-fold) CT; a slight inhibition, dependent on ATP but independent of Ca2+ and diolein, was observed. Our results suggest that intracellular release of free fatty acids or direct phosphorylation of CT by PKC probably do not account for the observed levels of stimulation by phorbol esters. Other possible mechanisms are discussed.

scholarly journals The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
David Barneda ◽  
Joan Planas-Iglesias ◽  
Maria L Gaspar ◽  
Dariush Mohammadyani ◽  
Sunil Prasannan ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Lipid Droplet ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Adipocyte Differentiation ◽  
Neutral Lipids ◽  
Brown Adipocyte ◽  
Amphipathic Helix ◽  
Tight Coupling ◽  
Brown Adipocytes

Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD–LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.

scholarly journals Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Valeria Zoni ◽  
Rasha Khaddaj ◽  
Pablo Campomanes ◽  
Abdou Rachid Thiam ◽  
Roger Schneiter ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Fluorescence Microscopy ◽  
Conceptual Understanding ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Yeast Genetics ◽  
Triglyceride Accumulation ◽  
Acyl Chains ◽  
And Function ◽  
Er Homeostasis

Cells store energy in the form of neutral lipids (NLs) packaged into micrometer-sized organelles named lipid droplets (LDs). These structures emerge from the endoplasmic reticulum (ER) at sites marked by the protein seipin, but the mechanisms regulating their biogenesis remain poorly understood. Using a combination of molecular simulations, yeast genetics, and fluorescence microscopy, we show that interactions between lipids’ acyl-chains modulate the propensity of NLs to be stored in LDs, in turn preventing or promoting their accumulation in the ER membrane. Our data suggest that diacylglycerol, which is enriched at sites of LD formation, promotes the packaging of NLs into LDs, together with ER-abundant lipids, such as phosphatidylethanolamine. On the opposite end, short and saturated acyl-chains antagonize fat storage in LDs and promote accumulation of NLs in the ER. Our results provide a new conceptual understanding of LD biogenesis in the context of ER homeostasis and function.

scholarly journals Computational metabolomics illuminates the lineage-specific diversification of resin glycoside acylsugars in the morning glory (Convolvulaceae) family

2021 ◽  
Author(s):  
Lars H. Kruse ◽  
Alexandra A. Bennett ◽  
Elizabeth H. Mahood ◽  
Elena Lazarus ◽  
Se Jin Park ◽  
...  
Keyword(s):  
Structural Diversity ◽  
Morning Glory ◽  
Resonance Spectroscopy ◽  
Leaf Extracts ◽  
Evolutionary Mechanisms ◽  
Defense Compounds ◽  
Resin Glycoside ◽  
Ring Structures ◽  
Acyl Chains ◽  
Fragmentation Patterns

AbstractAcylsugars are a class of plant defense compounds produced across many distantly related families. Members of the horticulturally important morning glory (Convolvulaceae) family produce a diverse sub-class of acylsugars called resin glycosides (RGs), which comprise oligosaccharide cores, hydroxyacyl chain(s), and decorating aliphatic and aromatic acyl chains. While many RG structures are characterized, the extent of structural diversity of this class in different genera and species is not known. In this study, we asked whether there has been lineage-specific diversification of RG structures in different Convolvulaceae species that may suggest diversification of the underlying biosynthetic pathways. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed from root and leaf extracts of 26 species sampled in a phylogeny-guided manner. LC-MS/MS revealed thousands of peaks with signature RG fragmentation patterns with one species producing over 300 signals, mirroring the diversity in Solanaceae-type acylsugars. A novel RG from Dichondra argentea was characterized using Nuclear Magnetic Resonance spectroscopy, supporting previous observations of RGs with open hydroxyacyl chains instead of closed macrolactone ring structures. Substantial lineage-specific differentiation in utilization of sugars, hydroxyacyl chains, and decorating acyl chains was discovered, especially among Ipomoea and Convolvulus – the two largest genera in Convolvulaceae. Adopting a computational, knowledge-based strategy, we further developed a high-recall workflow that successfully explained ~72% of the MS/MS fragments, predicted the structural components of 11/13 previously characterized RGs, and partially annotated ~45% of the RGs. Overall, this study improves our understanding of phytochemical diversity and lays a foundation for characterizing the evolutionary mechanisms underlying RG diversification.

scholarly journals Sleep disorders interactions with obesity and type 2 diabetes

2020 ◽  
Vol 16 (4) ◽  
pp. 25-30
Author(s):  
Tatyana O. Brodovskaya ◽  
Irina F. Grishina ◽  
Genia G. Babykina ◽  
Olga V. Nikolaenko ◽  
Egor A. Kovin ◽  
...  
Keyword(s):  
Sleep Disorders ◽  
Sleep Duration ◽  
Type Ii Diabetes ◽  
Sleep Disturbances ◽  
Metabolic Disorders ◽  
Cardiovascular Complications ◽  
Current Data ◽  
Type Ii ◽  
Obesity And Diabetes ◽  
Modifiable Factors

Obesity and type II diabetes are 21st century pandemia. These metаbolic disorders are in the focus of attention of various specialties: cardiologists, endocrinologists, nutritionists, therapists, and others. The high incidence of obesity and type II diabetes cardiovascular complications, such as myocardial infarction, stroke, chronic heart failure, dementia, determine the call of risk factors search. Modifiable factors may include sleep disturbances. Recent studies have revealed a connection between changes in sleep duration and metabolic disorders. However, to date, the mechanisms underlying this association have not been established. The aim of the review is to summarize existing epidemiological and experimental observations, as well as an analysis of possible pathophysiological mechanisms linking sleep duration with obesity and type II diabetes. The article considers current data suggesting a bi-directional association of sleep disorders with obesity and diabetes. Sleep disturbances are significant determinant of developing metabolic disorders. Sleep duration correction as one of therapeutic targets for cardiovascular complications of obesity and type II diabetes prevention.

scholarly journals Biochemical studies on cell fusion. I. Lipid composition of fusion-resistant cells.

1985 ◽  
Vol 101 (4) ◽  
pp. 1578-1590 ◽  
Author(s):  
D S Roos ◽  
P W Choppin
Keyword(s):  
Lipid Composition ◽  
Neutral Lipids ◽  
Mutant Cell ◽  
Ether Lipid ◽  
Resistant Cell ◽  
Fatty Acyl ◽  
Resistant Cell Line ◽  
Parental Line ◽  
Acyl Chains ◽  
Resistant Cells

A series of stable cell mutants of mouse fibroblasts were previously isolated (Roos, D. S. and R. L. Davidson, 1980, Somatic Cell Genet., 6:381-390) that exhibit varying degrees of resistance to the fusion-inducing effect of polyethylene glycol (PEG), but are morphologically similar to the parental cells from which they were derived. Biochemical analysis of these mutant cell lines has revealed differences in whole cell lipid composition which are directly correlated with their susceptibility to fusion. Fusion-resistant cells contain elevated levels of neutral lipids, particularly triglycerides and an unusual ether-linked lipid, O-alkyl, diacylglycerol. This ether lipid is increased approximately 35-fold over parental cells in the most highly PEG-resistant cell line. Fusion-resistant cells also contain more highly saturated fatty acyl chains (ratio of saturated to polyunsaturated fatty acids [S/P ratio] approximately 4:1) than the parental line (S/P ratio approximately 1:1). Cells which are intermediate in their resistance to PEG have ether lipid and fatty acid composition which is intermediate between the parental cells and the most fusion-resistant mutants. In a related communication (Roos, D. S. and P. W. Choppin, 1985, J. Cell. Biol., 100:1591-1598) evidence is presented that alteration of lipid content can predictably control the fusion response of these cells.

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