Lipidomic Analysis of Oxygenated Polyunsaturated Fatty Acid–Derived Inflammatory Mediators in Neurodegenerative Diseases

2020 ◽  
pp. 121-141
Author(s):  
Mauricio Mastrogiovanni ◽  
Estefanía Ifrán ◽  
Andrés Trostchansky ◽  
Homero Rubbo
Keyword(s):  
Fatty Acid ◽  
Neurodegenerative Diseases ◽  
Polyunsaturated Fatty Acid ◽  
Inflammatory Mediators ◽  
Lipidomic Analysis

scholarly journals Lipidomic Assessment of Triacylglycerol and Cholesterol Ester Species After n-3 Polyunsaturated Fatty Acid Suppementation in Humans: Comparison of Response Phenotypes

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 450-450
Author(s):  
Matthew Picklo ◽  
Michael Bukowski ◽  
Bastien Vallée Marcotte ◽  
Frédéric Guénard ◽  
Marie-Claude Vohl
Keyword(s):  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Cholesterol Ester ◽  
Cholesteryl Esters ◽  
Lower Mass ◽  
Phenotypic Differences ◽  
Lipidomic Analysis ◽  
Funding Sources ◽  
Response Phenotype ◽  
Insight Into

Abstract Objectives Assess the differences in triacylglycerol (TAG) and cholesterol ester (CE) species in the plasma of individuals displaying heterogeneous lipid responses following long chain n-3 (LCn-3) polyunsaturated fatty acid supplementation. Methods We performed a targeted, mass spectrometry (MS), infusion-based lipidomic analysis on plasma samples obtained from a clinical study in which participants were supplemented with 3 g/day of LCn-3 in the form of fish oil capsules over a 6-week period. Triacylglycerol (TAG) species and cholesteryl esters (CE) were quantified for 130 participants pre- and post-supplementation. Results Based on the change of total TAG concentrations following supplementation, participants were segregated into three response phenotypes: (1) positive responders (R+; TAG decrease < 10%), (2) non-responders (NR; TAG changes +/− 10%), and (3) negative responders (R−; TAG increase > 10%) representing 87/130 (67%), 24/130 (18%), and 19/130 (15%) of the study samples, respectively. There were no phenotypic differences for age, sex, body-mass index, glycemia, or ApoB concentrations. Sparse partial least squares discriminant analysis separated the three phenotypes with component 1 attributed to changes in TAG 50–53: X with 0–3 desaturations with R + having reductions in these TAG. Separation along component 2 identified lower mass TAG 46–48: X with 1–3 desaturations likely containing 14:0. This latter effect impacted mostly NR and R- phenotypes. Analysis of individual TAG species per response phenotype revealed TAG species that did not align with the overall TAG response phenotype. Using the TAG response phenotype for grouping, we performed SPLDA analysis for CE responses. We observed that distinction of the TAG response phenotypes qualitatively applies to CE in which separation along component 1 (65% of variance) was due to differences in CE 18:0, 18:1, and 14:0. CE 20:5 was elevated equally (>300%) between all phenotypes indicating LCn-3 intake. However, CE 22:6 was elevated R− (86%) to a greater extent vs. Res+ (55%) and NR (49%) phenotypes. Conclusions Our data identify lipidomic signatures (TAG and CE) associated with LCn-3 response phenotypes in humans and provide insight into the variability of lipid metabolism in humans. Funding Sources USDA-NIFA, USDA-ARS and CIHR MOP-229,488.

scholarly journals αS oligomers generated from polyunsaturated fatty acid and dopamine metabolite differentially interact with Aβ to enhance neurotoxicity

2021 ◽  
Author(s):  
Shailendra Dhakal ◽  
Jhinuk Saha ◽  
Courtney E Wyant ◽  
Vijayaraghavan Rangachari
Keyword(s):  
Fatty Acid ◽  
Neurodegenerative Diseases ◽  
Polyunsaturated Fatty Acid ◽  
Neuroblastoma Cells ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Proteinase K ◽  
Molecular Events ◽  
Clinical Presentations ◽  
Aβ Aggregation

It is increasingly becoming clear that neurodegenerative diseases are not as discrete as originally thought to be but rather display significant overlap in histopathological and clinical presentations. For example, nearly half of the patients with Alzheimer disease (AD) and synucleinopathies such as Parkinson disease (PD) show symptoms and pathological features of one another. Yet, the molecular events and features that underlie such comorbidities in neurodegenerative diseases remain poorly understood. Here, inspired to uncover the molecular underpinnings of the overlap between AD and PD, we investigated the interactions between amyloid-β (Aβ) and α-synuclein (αS), aggregates of which form the major components of amyloid plaques and Lewy bodies, respectively. Specifically, we focused on αS oligomers generated from the dopamine metabolite called dihydroxyphenylacetaldehyde (DOPAL), and a polyunsaturated fatty acid docosahexaenoic acid (DHA). Both αS oligomers showed structural and conformational differences confirmed by their disparity in size, secondary structure, susceptibility to proteinase K digestion and cytotoxicity. More importantly, the two oligomers differentially modulated Aβ aggregation. While both oligomers inhibited Aβ aggregation to varying extents, they induced structurally different Aβ assemblies. Furthermore, Aβ seeded with DHA-derived αS oligomers showed greater toxicity than DOPAL-derived αS oligomers in SH-SY5Y neuroblastoma cells. These results provide insights into the interactions between two amyloid proteins with empirically distinctive biophysical and cellular manifestations, enunciating a basis for potentially ubiquitous cross-amyloid interactions across many neurodegenerative diseases.

scholarly journals Electrophilic Cyclopentenone Neuroprostanes Are Anti-inflammatory Mediators Formed from the Peroxidation of the ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid

2008 ◽  
Vol 283 (29) ◽  
pp. 19927-19935 ◽  
Author(s):  
Erik S. Musiek ◽  
Joshua D. Brooks ◽  
Myungsoo Joo ◽  
Enrico Brunoldi ◽  
Alessio Porta ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Polyunsaturated Fatty Acid ◽  
Inflammatory Mediators ◽  
Anti Inflammatory

The effects of low-ratio n-6/n-3 PUFA on biomarkers of inflammation: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Yali Wei ◽  
Yan Meng ◽  
Na Li ◽  
Qian Wang ◽  
Liyong Chen
Keyword(s):  
Systematic Review ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Meta Analysis ◽  
Chain Polyunsaturated Fatty Acid ◽  
Inflammation Markers ◽  
Pufa Supplementation ◽  
Long Chain

The purpose of the systematic review and meta-analysis was to determine if low-ratio n-6/n-3 long-chain polyunsaturated fatty acid (PUFA) supplementation affects serum inflammation markers based on current studies.

Selected gene – polyunsaturated fatty acid interactions and risk of obesity

2010 ◽  
Vol 72 (08/09) ◽  
Author(s):  
C Jourdan ◽  
S Kloiber ◽  
H Himmerich ◽  
C Gieger ◽  
H Wichmann ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Polyunsaturated Fatty Acid
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