Parallel metabolomics and lipidomics enables the comprehensive study of mouse brain regional metabolite and lipid patterns

Yu, Huaxu; Villanueva, Nathaniel L.; Bittar, Thibault P.; Arsenault, Elizabeth; Labonté, Benoit; Huan, Tao

doi:10.1016/j.aca.2020.09.051

Cited by 24 publications

(22 citation statements)

References 45 publications

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“…The authors used a similar Folsch-type extraction method but a different chromatography method (HILIC) that did not detect the TG portions of the brain extracts. Their results at the class level were also in accordance with the results reported here and with other studies investigating brain lipid composition [ 1 , 5 , 25 ].…”

Section: Discussionsupporting

confidence: 93%

“…The brain is a heterogeneous organ and a critical part of the central nervous system. It controls not only the essential bodily functions such as breathing and other metabolic functions but is also responsible for learning and memory, behavior, and thoughts [ 1 ]. The brain is the second most lipid-rich organ in the mammalian body [ 2 ] and is composed of numerous lipid classes, such as phospholipids, sphingolipids, ceramides and triacylglycerides (TG) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…These lipids have important functions, including cellular signaling, forming the lipid bilayers of cellular membranes, and energy storage [ 4 ]. Its complex structures and functions are also reflected by the many lipid species detected [ 1 , 5 , 6 , 7 ]. However, the regulation of the brain lipidome and its functions in metabolism and signaling are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Impacts of Formula Supplemented with Milk Fat Globule Membrane on the Neurolipidome of Brain Regions of Piglets

et al. 2022

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The milk fat globule membrane (MFGM) appears to play an important role in infant neurocognitive development; however, its mechanism(s) of action remains unclear. This study aimed to investigate the role of a dietary MFGM supplement on the lipid profiles of different neonatal brain regions. Ten-day-old male piglets (4–5 kg) were fed unsupplemented infant formula (control, n = 7) or an infant formula supplemented with low (4%) or high (8%) levels of MFGM (n = 8 each) daily for 21 days. Piglets were then euthanized, and brain tissues were sectioned. Untargeted liquid chromatography-mass spectrometry lipidomics was performed on the cerebellum, hippocampus, prefrontal cortex, and the rest of the brain. The analyses identified 271 and 171 lipids using positive and negative ionization modes, respectively, spanning 16 different lipid classes. MFGM consumption did not significantly alter the lipidome in most brain regions, regardless of dose, compared to the control infant formula. However, 16 triacylglyceride species were increased in the hippocampus (t-test, p-value < 0.05) of the high-supplemented piglets. Most lipids (262 (96.7%) and 160 (93.6%), respectively) differed significantly between different brain regions (ANOVA, false discovery rate corrected p-value < 0.05) independent of diet. Thus, this study highlighted that dietary MFGM altered lipid abundance in the hippocampus and detected large differences in lipid profiles between neonatal piglet brain regions.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impacts of Formula Supplemented with Milk Fat Globule Membrane on the Neurolipidome of Brain Regions of Piglets

et al. 2022

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“…Although some methodologies analyze these small molecules together, lipids are unlike metabolites in that they usually display low polarity and high hydrophobicity. Hence, conducting independent comprehensive analyses of these two groups offers the possibility of optimizing the separation and detection conditions tailored to each type of molecules. − …”

Section: Introductionmentioning

confidence: 99%

Comprehensive Serum Lipidomics for Detecting Incipient Dementia in Parkinson’s Disease

et al. 2021

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While a number of methods are available for analyzing lipids, unbiased untargeted lipidomics with high coverage remains a challenge. In this work, we report a study of isotopestandard-assisted liquid chromatography mass spectrometry lipidomics of serum for biomarker discovery. We focus on Parkinson's disease (PD), a neurodegenerative disorder that often progresses to dementia. Currently, the diagnosis of PD is purely clinical and there is limited ability to predict which PD patients will transition to dementia, hampering early interventions. We studied serum samples from healthy controls and PD patients with no clinical signs of dementia. A follow-up 3 years later revealed that a subset of PD patients had transitioned to dementia. Using the baseline samples, we constructed two biomarker panels to differentiate (1) PD patients from healthy controls and (2) PD patients that remained cognitively stable from PD patients with incipient dementia (diagnosed 3 years after sample collection). The proposed biomarker panels displayed excellent performance and may be useful for detecting prodromal PD dementia, allowing early interventions and prevention efforts. The biochemistry of significantly changed lipids is also discussed within the current knowledge of neurological pathologies. Our results are promising and future work using a larger cohort of samples is warranted.

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“…Although there is one existing dual protocol for human cells (Jurkat T cells) [16], this was not optimised for the classes of metabolites that were of interest to us since it focused on central carbon and nitrogen metabolism, whereas brain-specific molecules such as homocarnosine, N-acetylaspartate, gamma-aminobutyric acid, and lipids were known to be important in brain tumours [11,[22][23][24][25][26]. In particular, a large volume of the non-aqueous, less polar solvent is needed to fully extract the lipids from brain tissue [27]. Two existing single extraction and four dual extraction protocols were critically assessed based on their practical reproducibility, the suitability of the metabolite extraction protocol to human cancer cells and their RNA recovery.…”

Section: Introductionmentioning

confidence: 99%

Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues

et al. 2021

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The integration of untargeted metabolomics and transcriptomics from the same population of cells or tissue enhances the confidence in the identified metabolic pathways and understanding of the enzyme–metabolite relationship. Here, we optimised a simultaneous extraction method of metabolites/lipids and RNA from ependymoma cells (BXD-1425). Relative to established RNA (mirVana kit) or metabolite (sequential solvent addition and shaking) single extraction methods, four dual-extraction techniques were evaluated and compared (methanol:water:chloroform ratios): cryomill/mirVana (1:1:2); cryomill-wash/Econospin (5:1:2); rotation/phenol-chloroform (9:10:1); Sequential/mirVana (1:1:3). All methods extracted the same metabolites, yet rotation/phenol-chloroform did not extract lipids. Cryomill/mirVana and sequential/mirVana recovered the highest amounts of RNA, at 70 and 68% of that recovered with mirVana kit alone. sequential/mirVana, involving RNA extraction from the interphase of our established sequential solvent addition and shaking metabolomics-lipidomics extraction method, was the most efficient approach overall. Sequential/mirVana was applied to study a) the biological effect caused by acute serum starvation in BXD-1425 cells and b) primary ependymoma tumour tissue. We found (a) 64 differentially abundant metabolites and 28 differentially expressed metabolic genes, discovering four gene-metabolite interactions, and (b) all metabolites and 62% lipids were above the limit of detection, and RNA yield was sufficient for transcriptomics, in just 10 mg of tissue.

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Parallel metabolomics and lipidomics enables the comprehensive study of mouse brain regional metabolite and lipid patterns

Cited by 24 publications

References 45 publications

Impacts of Formula Supplemented with Milk Fat Globule Membrane on the Neurolipidome of Brain Regions of Piglets

Impacts of Formula Supplemented with Milk Fat Globule Membrane on the Neurolipidome of Brain Regions of Piglets

Comprehensive Serum Lipidomics for Detecting Incipient Dementia in Parkinson’s Disease

Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues

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