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The emerging field of lipidomics

An Erratum to this article was published on 01 September 2005

Key Points

  • Lipids are important small-molecule metabolites that have roles in a wide variety of physiological processes.

  • Deregulation of lipid metabolism leads to onset of pathology, including many forms of cancer, diabetes and neurodegenerative diseases.

  • Genetics, cell biology and biochemistry have fundamentally advanced our understanding of the biology of lipids in recent years.

  • Novel methodologies for the biochemical analysis of lipids and their effectors will substantially further the field of lipid research, in particular at systems-level scale (lipidomics) approaches.

  • These technologies are valuable tools at various stages of the drug development process, most importantly in target discovery and biomarker development.

  • One of the major advantages of biochemical lipidomics, which aims at measuring lipid metabolites and their effectors, is that it might directly lead to the identification pathways of lipid action or lipid metabolism.

Abstract

The crucial role of lipids in cell, tissue and organ physiology is demonstrated by a large number of genetic studies and by many human diseases that involve the disruption of lipid metabolic enzymes and pathways. Examples of such diseases include cancer, diabetes, as well as neurodegenerative and infectious diseases. So far, the explosion of information in the fields of genomics and proteomics has not been matched by a corresponding advancement of knowledge in the field of lipids, which is largely due to the complexity of lipids and the lack of powerful tools for their analysis. Novel analytical approaches — in particular, liquid chromatography and mass spectrometry — for systems-level analysis of lipids and their interacting partners (lipidomics) now make this field a promising area of biomedical research, with a variety of applications in drug and biomarker development.

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Figure 1
Figure 2: Lipidomics — systems-level scale analysis of lipids and their interactors.
Figure 3: The molecular biology of lipids.
Figure 4: Mass spectrometric profiling of lipids in complex mixtures derived from tissue and cell extracts.
Figure 5: Lipidomics in drug development.

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Acknowledgements

I would like to thank all members of our group and those of the labs of G. Di Paolo, M. Kemeny and U.-A. Boelsterli, as well as the external reviewers for their constructive comments. Work in our laboratory is supported by research grants from the National University of Singapore, the National Medical Research Council of Singapore and the Novartis Institutes for Tropical Research.

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DATABASES

Entrez Gene

Cathepsin D

CB1 cannabinoid receptor

GLUT4

HNFA4

LXR

PI3 kinase

PPARγ

PTEN

SK1

VEGF

OMIM

Alzheimer's disease

early-onset Parkinson's disease

multiple myeloma

Niemann–Pick disease type C

Parkinson's disease

schizophrenia

FURTHER INFORMATION

Alliance for Cell Signalling

Cyber Lipid Center

European Lipidomics Initiative

Kansas Lipodomics Research Center

LIPIDAT

Lipid Bank

Lipid Library – All About Lipids

Lipid MAPS

Lipomics

Lipid Profiles

MUSC Lipodomics Core Facility

Glossary

LIPIDOMICS

Systems-level analysis and characterization of lipids and their interacting moieties.

SYSTEMS BIOLOGY

A discipline that aims at deciphering relationships between different parts of a biological system (for example, a metabolic chain, cell or tissue) with the goal of understanding (and predicting) the behaviour of the system as a whole.

INTERFACIAL CATALYSIS

Enzymatic catalysis at an interface, such as the surface of a biological membrane.

PH DOMAIN

Pleckstrin homology domain. A widespread and functionally diverse protein fold that mediates intermolecular interactions, most notably with phosphoinositides.

LIPID MEDIATOR

A lipid molecule that mediates a biological response. Lipid mediators form distinct classes of bioactive molecules rather than mere intermediates of lipid metabolism (for example, arachidonic acid metabolites (eicosanoids) or platelet-activating factor).

NEUROTRANSMITTER

A chemical that transmits information from a neuron to a neighbouring cell.

GANGLIOSIDE

Complex glycosphingolipids that carry three or more sugars on a ceramide backbone. Some of the sugars include sialic acid and N-acetylneuranimic acid.

TANDEM MASS SPECTROMETRY

Methods that include at least two stages of mass analysis, in conjunction with a dissociation process.

THIN-LAYER CHROMATOGRAPHY

Commonly used chromatographic method. Analyte is separated by chromatographic material, which is immobilized as a thin layer on a solid support such a glass plate.

LIPOSOMES

Small (nm–μm) spherical particles that are composed of lipid bilayers. Liposomes are used in biophysical and biochemical binding studies, as carriers in drug delivery and cosmetic formulations.

ANANDAMIDE

An endocannabinoid arachidonic acid metabolite (arachidonylethanolamine).

METABOLOMICS/METABONOMICS

A discipline that aims at the quantitative and comprehensive analysis of all metabolites. Although the term 'metabolomic' is used here no side is taken with respect to the distinction between the two terms.

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Wenk, M. The emerging field of lipidomics. Nat Rev Drug Discov 4, 594–610 (2005). https://doi.org/10.1038/nrd1776

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