Abstract
Background
Lipids play key roles in numerous biological processes, including energy storage, cell membrane structure, signaling, immune responses, and homeostasis, making lipidomics a vital branch of metabolomics that analyzes and characterizes a wide range of lipid classes. Addressing the complex etiology, age-related risk, progression, inflammation, and research overlap in conditions like Alzheimer's Disease, Parkinson’s Disease, Cardiovascular Diseases, and Cancer poses significant challenges in the quest for effective therapeutic targets, improved diagnostic markers, and advanced treatments. Mass spectrometry is an indispensable tool in clinical lipidomics, delivering quantitative and structural lipid data, and its integration with technologies like Liquid Chromatography (LC), Magnetic Resonance Imaging (MRI), and few emerging Matrix-Assisted Laser Desorption Ionization- Imaging Mass Spectrometry (MALDI-IMS) along with its incorporation into Tissue Microarray (TMA) represents current advances. These innovations enhance lipidomics assessment, bolster accuracy, and offer insights into lipid subcellular localization, dynamics, and functional roles in disease contexts.
Aim of the review
The review article summarizes recent advancements in lipidomic methodologies from 2019 to 2023 for diagnosing major neurodegenerative diseases, Alzheimer’s and Parkinson’s, serious non-communicable cardiovascular diseases and cancer, emphasizing the role of lipid level variations, and highlighting the potential of lipidomics data integration with genomics and proteomics to improve disease understanding and innovative prognostic, diagnostic and therapeutic strategies.
Key scientific concepts of review
Clinical lipidomic studies are a promising approach to track and analyze lipid profiles, revealing their crucial roles in various diseases. This lipid-focused research provides insights into disease mechanisms, biomarker identification, and potential therapeutic targets, advancing our understanding and management of conditions such as Alzheimer's Disease, Parkinson’s Disease, Cardiovascular Diseases, and specific cancers.
Graphical abstract
Lipidome analysis methodology in major diseases and discovery of therapeutics and biomarkers
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Data availability
A data availability statement is not applicable since this review does not involve original data collection. All discussed data are sourced from existing literature and are publicly available.
Abbreviations
- 2HG :
-
2-Hydroxyglutarate
- AA :
-
Arachidonic acid
- ACC1 :
-
Acetyl-Coenzyme A carboxylase 1
- ACLY :
-
ATP citrate lyase
- AD :
-
Alzheimer’s Disease
- AdA:
-
Adrenic acid
- AHA :
-
American Heart Association
- AKT YapS127A :
-
Protein Kinase B/Yes-associated protein 1 (mutated)
- AMPK :
-
AMP-activated protein kinase
- apoA-I :
-
Apolipoprotein A-I
- APP :
-
Amyloid Precursor Protein
- ASCVD :
-
Atherosclerotic cardiovascular disease
- ATP :
-
Adenosine triphosphate
- AUC :
-
Area Under the ROC Curve
- Bax :
-
Bcl-2-associated X protein
- BCFA :
-
Branched-chain Fatty Acid
- BCL2 :
-
B-cell lymphoma 2
- Bcl-xL :
-
B-cell lymphoma-extra large
- CD274 :
-
Cluster of differentiation 274
- CE:
-
Cholesterol ester
- Cer:
-
Ceramide
- CLRD :
-
Chronic Lower Respiratory Disease
- CRC :
-
Colorectal Cancer
- CSC :
-
Cancer Stem Cell
- CSF :
-
Cerebrospinal Fluid
- CTLA4 :
-
Cytotoxic T-lymphocyte–associated antigen 4
- CVD :
-
Cardiovascular Disease
- DDA :
-
Data-Dependent Acquisition
- DHA:
-
Docosahexaenoic acid
- DIA :
-
Data-Independent Acquisition
- ECM :
-
Extracellular matrix
- ELOVL6 :
-
Long-chain fatty acids family member 6
- EPA:
-
Eicosapentaenoic acid
- FA:
-
Fatty acid
- FABP5 :
-
Fatty acid-binding protein 5
- FADS1 :
-
Fatty acid desaturases 1
- FADS2 :
-
Fatty acid desaturases 2
- FASN :
-
Fatty Acid Synthase
- FIA-MS/MS :
-
Flow Injection Analysis Tandem Mass Spectrometry
- FTICR :
-
Fourier-transform ion cyclotron resonance
- GC :
-
Gas Chromatography
- GC :
-
Gastric cancer
- GL:
-
Glycerolipid
- GP:
-
Glycerophospholipid
- GPX4 :
-
Glutathione peroxidase 4
- HAVCR2 :
-
Hepatitis A virus cellular receptor 2
- HDL-C :
-
High-density lipoprotein Cholesterol
- HER2 :
-
Human epidermal growth factor receptor 2
- HETE :
-
Hydroxyeicosatetraenoic acid
- HexCer:
-
Hexosylceramides
- HILIC :
-
Hydrophilic interaction liquid chromatography
- HRMS :
-
High Resolution Mass Spectrometry
- HR-MS :
-
Shotgun high-resolution mass spectrometry
- HSL :
-
Hormone-sensitive lipase
- ICC :
-
Intrahepatic cholangiocarcinoma
- IDL:
-
Intermediate-Density Lipoproteins
- IS :
-
Internal Standard
- KAROLA :
-
Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung
- KRAS :
-
Ki-ras2 Kirsten rat sarcoma virus
- LAG3:
-
Lymphocyte activating 3 gene
- LC :
-
Liquid Chromatography
- LC-ESI MS :
-
Liquid Chromatography – Electrospray Ionization Mass Spectrometry
- LC–MS/MS :
-
Liquid Chromatography – Tandem Mass Spectrometry
- LDL:
-
Low-density lipoprotein
- LDL-C :
-
Low-density lipoprotein Cholesterol
- LDLR :
-
Low-density Lipoprotein Receptor
- LIPID :
-
Long-Term Intervention with Pravastatin in Ischaemic Disease
- LM :
-
Lipid Mediator
- LMN :
-
LipidMatch Normalization
- LPC/LysoPC :
-
Lysophosphatidylcholine
- LPE:
-
Lysophosphatidylethanolamine
- LPI:
-
Lysophosphatidylinositol
- LR-MS:
-
Shotgun low-resolution mass spectrometry
- LSI :
-
Lipidomics Standard Initiative
- MALDI-IMS :
-
Matrix Assisted Laser Desorption Ionization – Imaging Mass Spectrometry
- MAPK :
-
Mitogen-activated protein kinase/
- MCI :
-
Mild Cognitive Impairment
- MHC :
-
Monohexosylceramide
- mIDH1 :
-
Cytosolic isocitrate dehydrogenase 1
- MPTP :
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- MRI :
-
Magnetic Resonance Imaging
- MRI-MS :
-
Magnetic Resonance Imaging – Mass Spectrometry
- MRM :
-
Multiple Reaction Monitor
- MRS :
-
Magnetic Resonance Spectrometry
- MS-DIAL :
-
Mass Spectrometry – Data Independent Analysis
- MSI :
-
Mass Spectrometry Imaging
- MTBE :
-
Methyl tert-butyl ether
- mTORC2 :
-
Mammalian target of rapamycin complex 2
- MUFA:
-
Monounsaturated fatty acids
- NFT :
-
Neurofibrillary tangles
- NMR :
-
Nuclear Magnetic Resonance
- OCFA:
-
Odd-chain Fatty Acid
- PA:
-
Phosphatidic acid
- PAG :
-
Phenylacetylglutamine
- PC:
-
Phosphatidylcholine
- PCA :
-
Principal Component Analysis
- PD :
-
Parkinson’s Disease
- PDCD1 :
-
Programmed cell death 1
- PE:
-
Phosphatidylethanolamine
- PI:
-
Phosphatidylinositol
- PL:
-
Phospholipid
- PPARα :
-
Peroxisome proliferator-activated receptor alpha
- PPARγ-ACLY/ACC :
-
Peroxisome proliferator-activated receptor gamma ATP-citratelyase/acetyl-CoA carboxylase
- PQN :
-
Probabilistic Quotient Normalization
- PRM :
-
Parallel Reaction Monitor
- PS:
-
Phosphatidylserine
- PUFA:
-
Polyunsaturated fatty acids
- QQQ :
-
Triple Quadrupole
- Q-TOF :
-
Quadrupole Time-of-Flight
- ROC :
-
Receiver operating curve
- ROS :
-
Reactive Oxygen Species
- RPLC :
-
Reverse Phase Liquid Chromatography
- RP-UHPLC/MS :
-
Reversed-phase Ultra-high Performance Liquid Chromatography/Mass Spectrometry
- SCD1 :
-
Syndecan-1
- SFA:
-
Saturated fatty acids
- SILL :
-
Strategy Inventory of Language Learning
- SIM :
-
Single Ion Monitoring
- SM:
-
Sphingomyelin
- SREBP-1c :
-
Sterol regulatory element-binding protein 1
- STAT:
-
Signal Transducer and Activator of Transcription
- SWATH :
-
Sequence Window of All Theoretical Fragment Ion Spectra
- TG:
-
Triacylglycerol
- TIGIT :
-
T cell immunoreceptor with immunoglobulin and ITIM domain
- TIL :
-
Tumor Infiltrating Lymphocytes
- TIMS :
-
Trapped Ion Mobility Spectrometry
- TLC :
-
Thin layer Chromatography
- TMA :
-
Tissue Microarray
- TNBC :
-
Triple Negative Breast Cancer
- TVB-2640 :
-
Denifanstat
- UHPLC :
-
Ultra High-Performance Liquid Chromatography
- UHPSFC-MS :
-
Ultra-High Performance supercritical fluid chromatography/mass spectrometry
- UPLC-MS/MS :
-
Ultra-High Performance Liquid Chromatography – Tandem Mass Spectrometry
- USP22 :
-
Ubiquitin specific peptidase 22
- VLDL:
-
Very low-density lipoprotein
- WECAC :
-
The Western Norway Coronary Angiography Cohort
- Zeb1 :
-
Zinc-finger E-box-binding homeobox 1
- Zeb2 :
-
Zinc-finger E-box-binding homeobox 2
- αS :
-
Alpha-synuclein
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Sarkar, S., Roy, D., Chatterjee, B. et al. Clinical advances in analytical profiling of signature lipids: implications for severe non-communicable and neurodegenerative diseases. Metabolomics 20, 37 (2024). https://doi.org/10.1007/s11306-024-02100-7
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DOI: https://doi.org/10.1007/s11306-024-02100-7