Complex Lipids
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2021 ◽  
Author(s):  
Christopher R. Brydges ◽  
Sudeepa Bhattacharyya ◽  
Sia Mahmoudian Dehkordi ◽  
Yuri Milaneschi ◽  
Brenda Penninx ◽  
...  

Background: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions. Methods: Using three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism. Results: The IMD clinical dimension and the inflammatory index were positively correlated (r=0.19, p=.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids. Conclusion: The IMD dimension of depression is reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Alicja Pakiet ◽  
Kinga Sikora ◽  
Jarek Kobiela ◽  
Olga Rostkowska ◽  
Adriana Mika ◽  
...  

Abstract Background Accumulating evidence indicates alterations in lipid metabolism and lipid composition in neoplastic tissue. Earlier nuclear magnetic resonance studies showed that the contents of major lipid groups, such as triacylglycerols, phospholipids and cholesterol, are changed in colon cancer tissue. Methods In this study, a more detailed analysis of lipids in cancer and tumor adjacent tissues from colorectal cancer patients, using liquid chromatography–mass spectrometry, allowed for comparison of 199 different lipids between cancer tissue and tumor adjacent tissue using principal component analysis. Results Significant differences were found in 67 lipid compounds between the two types of tissue; many of these lipid compounds are bioactive lipids such as ceramides, lysophospholipids or sterols and can influence the development of cancer. Additionally, increased levels of phospholipids and sphingolipids were present, which are major components of the cell membrane, and increases in these lipids can lead to changes in cell membrane properties. Conclusions This study showed that many complex lipids are significantly increased or decreased in colon cancer tissue, reflecting significant alterations in lipid metabolism. This knowledge can be used for the selection of potential molecular targets of novel anticancer strategies based on the modulation of lipid metabolism and the composition of the cell membrane in colorectal cancer cells.


2021 ◽  
pp. 1-12
Author(s):  
S. G. B. Gowda ◽  
Y. Sasaki ◽  
E. Hasegawa ◽  
H. Chiba ◽  
S. P. Hui

Insects such as Tenebrio molitor have been considered an alternative source of nutrition for animals and have also been adopted as human food throughout history, especially in Asia and Africa. Lipids are the second most abundant component followed by proteins. However, studies focusing on comprehensive lipid composition analsysis of these widely reared species are limited. The untargeted lipidomic analysis of yellow mealworm larvae (T. molitor) led to the identification of several lipid molecular species from lipid classes such as: free fatty acids, sphingolipids, phospholipids, and triacylglycerols. The results revealed that polyunsaturated fatty acids (PUFAs) (45%) are the most abundant fatty acids, followed by monounsaturated fatty acids (MUFAs) (42%) and saturated fatty acids (13%). Fatty acids such as FA 18:1 and FA 18:2 are the most abundant fatty acids and are substantially enriched in other complex lipids in the form of esters. Moreover, functional lipids such as sphingomyelins, ceramides, cardiolipins, phosphatidylinositols, and phosphatidylethanolamines were characterised for the first time, with a large number of MUFAs and PUFAs as their main acyl chains. Overall, our data showed the occurrence of multiple structurally diverse lipids in T. molitor, suggesting that mealworms are not only enriched with proteins but also have several functional lipids, which are highly beneficial to human and animal health. Thus, the larvae of T. molitor could serve as a promising candidate for the development of functional food and feed products.


2021 ◽  
pp. 2004532
Author(s):  
Rupak Shivakoti ◽  
John W. Newman ◽  
Luke Elizabeth Hanna ◽  
Artur T. L. Queiroz ◽  
Kamil Borkowski ◽  
...  

IntroductionHost lipids play important roles in Tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well-characterised. We utilised unbiased lipidomics to study the prospective association of host lipids with TB treatment failure.MethodsA case-control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls.ResultsBaseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters (CE) and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two CE lipids combined in a unique classifier model provided an AUC of 0.79 (0.65–0.93) in the test dataset for prediction of TB treatment failure.ConclusionsWe identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. A lipid signature with prognostic accuracy for TB treatment failure was also identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring.


Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 330
Author(s):  
Timofey V. Malyarenko ◽  
Alla A. Kicha ◽  
Valentin A. Stonik ◽  
Natalia V. Ivanchina

Sphingolipids are complex lipids widespread in nature as structural components of biomembranes. Commonly, the sphingolipids of marine organisms differ from those of terrestrial animals and plants. The gangliosides are the most complex sphingolipids characteristic of vertebrates that have been found in only the Echinodermata (echinoderms) phylum of invertebrates. Sphingolipids of the representatives of the Asteroidea and Holothuroidea classes are the most studied among all echinoderms. In this review, we have summarized the data on sphingolipids of these two classes of marine invertebrates over the past two decades. Recently established structures, properties, and peculiarities of biogenesis of ceramides, cerebrosides, and gangliosides from starfishes and holothurians are discussed. The purpose of this review is to provide the most complete information on the chemical structures, structural features, and biological activities of sphingolipids of the Asteroidea and Holothuroidea classes.


2021 ◽  
Vol 12 (1) ◽  
pp. 68-78
Author(s):  
Kurnia Putri Utami ◽  
Widya Wasityastuti ◽  
Marsetyawan HNE Soesatyo

An immune system recognizes and responds to antigens entering the body. Maintaining these roles, components of the immune system need energy obtained from nutrients such as carbohydrates, proteins, and lipids. This study reviews and discusses roles of lipids, particularly fatty acids, in regulations of the immune system. This study was conducted by conducting a literature study on published research articles written in English. The articles were obtained from PubMed and Google Scholar by using search keywords: lipid, fatty acids, immune, regulation, inflammation, and response. Lipids are a group of biomolecule compounds composed of carbon, oxygen, and hydrogen, and they are classified into simple, compound and complex lipids. Fatty acids are compound lipids that act as a main fuel for metabolism, an essential component for all membranes, and a gene regulator. Fatty acids have a modulating effect on immune cells, such as: acting as a host defence, activating the immune system, interacting with nuclear transcription factors, playing roles in inflammatory responses, promoting apoptosis, as well as influencing lymphocyte proliferation, cytokine production, and Natural Killer (NK) cell activities. However, the modulation of the immune system by lipids is influenced by various factors such as concentration and types of fatty acids, types of immune cells, and species. This study is suggested to provide an overview of beneficial roles of lipids in maintaining immunity.


2021 ◽  
Author(s):  
Tagreed A Mazi ◽  
Kamil Borkowski ◽  
John W. Newman ◽  
Oliver Fiehn ◽  
Christopher L. Bowlus ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) is a progressive condition that includes steatosis (NAFL) and nonalcoholic steatohepatitis (NASH). In the U.S., Hispanics (HIS) are afflicted with NAFLD at a higher rate and severity compared to other ethnicities. To date, the mechanisms underlying this disparity have not been elucidated. In this pilot study, we compared untargeted plasma metabolomic profiles for primary metabolism, complex lipids, choline and related compounds between a group of HIS (n =7) and White Caucasian (CAU, n =8) subjects with obesity and biopsy-characterized NAFL to ethnicity-matched lean healthy controls (n =14 HIS and 8 CAU). We also compared liver and plasma metabolomic profiles in a group of HIS and CAU subjects with obesity and NASH of comparable NAFLD Activity Scores, to BMI-matched NASH-free subjects in both ethnicities. Results highlight signs of metabolic dysregulation observed in HIS, independent of obesity, including higher plasma triglycerides, acylcarnitines, and free fatty acids. With NASH progression, there were ethnicity-related differences in the hepatic profile, including higher free fatty acids and lysophospholipids seen in HIS, suggesting lipotoxicity is involved in the progression of NASH. We also observed greater hepatic triglyceride content, higher plasma triglyceride concentrations and lower hepatic phospholipids with signs of impaired hepatic mitochondrial β-oxidation. These findings provide preliminary evidence indicating ethnicity-related variations that could potentially modulate the risk for progression of NALD to NASH.


2021 ◽  
Vol 14 (2) ◽  
Author(s):  
David Rhainds ◽  
Chris J. Packard ◽  
Mathieu R. Brodeur ◽  
Eric J. Niesor ◽  
Frank M. Sacks ◽  
...  

Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 ( ADCY9 ) gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in ADCY9 on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse ADCY9 gene inactivation on cardiovascular physiology. Finally, we present our current model of the interaction between dalcetrapib and ADCY9 gene variants in the arterial wall macrophage, based on the intracellular role of CETP in the transfer of complex lipids from endoplasmic reticulum membranes to lipid droplets. Briefly, the concept is that dalcetrapib would inhibit CETP-mediated transfer of cholesteryl esters, resulting in a progressive inhibition of cholesteryl ester synthesis and free cholesterol accumulation in the endoplasmic reticulum. Reduced ADCY9 activity, by paradoxically leading to higher cyclic AMP levels and in turn increased cellular cholesterol efflux, could impart cardiovascular protection in rs1967309 AA patients. The ongoing dal-GenE trial recruited 6145 patients with the protective AA genotype and will provide a definitive answer to whether dalcetrapib will be protective in this population.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248964
Author(s):  
Jun-dae Kim ◽  
Lingping Zhu ◽  
Quan Sun ◽  
Longhou Fang

Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair of dysfunctional hydrated NAD(P)H, known as NAD(P)H(X). Importantly, AIBP deficiency contributes to lethal neurometabolic disorder, reminiscent of the Leigh syndrome in humans. Whereas cyclic NADPHX production is proposed to be the underlying cause, we hypothesize that an unbiased metabolic profiling may: 1) reveal new clues for the lethality, e.g., changes of mitochondrial metabolites., and 2) identify metabolites associated with new AIBP functions. To this end, we performed unbiased and profound metabolic studies of plasma obtained from adult AIBP knockout mice and control littermates of both genders. Our systemic metabolite profiling, encompassing 9 super pathways, identified a total of 640 compounds. Our studies demonstrate a surprising sexual dimorphism of metabolites affected by AIBP deletion, with more statistically significant changes in the AIBP knockout female vs male when compared with the corresponding controls. AIBP knockout trends to reduce cholesterol but increase the bile acid precursor 7-HOCA in female but not male. Complex lipids, phospholipids, sphingomyelin and plasmalogens were reduced, while monoacylglycerol, fatty acids and the lipid soluble vitamins E and carotene diol were elevated in AIBP knockout female but not male. NAD metabolites were not significantly different in AIBP knockout vs control mice but differed for male vs female mice. Metabolites associated with glycolysis and the Krebs cycle were unchanged by AIBP knockout. Importantly, polyamine spermidine, critical for many cellular functions including cerebral cortex synapses, was reduced in male but not female AIBP knockout. This is the first report of a systemic metabolite profile of plasma samples from AIBP knockout mice, and provides a metabolic basis for future studies of AIBP regulation of cellular metabolism and the pathophysiological presentation of AIBP deficiency in patients.


Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 202
Author(s):  
Penghui Lin ◽  
Li Dai ◽  
Daniel R. Crooks ◽  
Leonard M. Neckers ◽  
Richard M. Higashi ◽  
...  

Lipids comprise diverse classes of compounds that are important for the structure and properties of membranes, as high-energy fuel sources and as signaling molecules. Therefore, the turnover rates of these varied classes of lipids are fundamental to cellular function. However, their enormous chemical diversity and dynamic range in cells makes detailed analysis very complex. Furthermore, although stable isotope tracers enable the determination of synthesis and degradation of complex lipids, the numbers of distinguishable molecules increase enormously, which exacerbates the problem. Although LC-MS-MS (Liquid Chromatography-Tandem Mass Spectrometry) is the standard for lipidomics, NMR can add value in global lipid analysis and isotopomer distributions of intact lipids. Here, we describe new developments in NMR analysis for assessing global lipid content and isotopic enrichment of mixtures of complex lipids for two cell lines (PC3 and UMUC3) using both 13C6 glucose and 13C5 glutamine tracers.


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