LIPID MAPS 2011: Lipidomics delivers
Lipidomics Gateway (25 May 2011) [doi:10.1038/lipidmaps.2011.16]
This year's conference confirms that other fields are appreciating the importance of lipidomics.
Reflecting the broad impact of lipidomics, the title of this year's LIPID MAPS Annual Meeting was Lipidomics Impact on Cell Biology, Cancer and Metabolic Diseases. This article describes some of the highlights of the meeting.
In a sign that the field is maturing, lipidomics has now progressed to population-level studies. David W. Russell presented some initial results of the Dallas Heart Study, in which new lipidomic methods were developed to characterize blood plasma sterol levels in thousands of individuals. The team are now comparing these with the individuals' genetics. Unexpected associations and new biomarkers are sure to emerge.
Delegates particularly enjoyed Jerrold M. Olefsky's elegant demonstration of how inflammation, rather than obesity, causes insulin resistance. He presented a neat model of how the omega-3 polyunsaturated fatty acids, such as DHA, interrupt inflammation by acting on the GPR120 receptor. This story illustrates the central role that lipids play in inflammatory processes that are important in many diseases.
Now that lipidomics is truly up and running, a subject on many minds is how to most usefully store and visualize such vast amounts of data. Edward A. Dennis gave the audience a feel for how lipid heat maps can be useful in this capacity. He also explained how researchers can now compare the abundance of hundreds of lipid species, not only through time and in response to different stimuli but also between cell types. As many hoped, the first large-scale study — the mouse macrophage lipidome — has given birth to several new projects, many of which were presented as posters. One example, described in Shankar Subramaniam's talk, is the calculation from lipidomic data of accurate rate constants for enzymes throughout the lipid biosynthetic network.
Atherosclerosis and inflammation
In the opening session, Jay D. Horton discussed his group's recent discovery of the different roles played by two proteins, S14 and MIG12, in regulating the polymerization and activity of the first committed enzyme in fatty acid biosynthesis — acetyl-CoA carboxylase. Later, Robert C. Murphy demonstrated how mass spectrometry combined with imaging can be used to measure the abundance of lipids, such as oxidised cholesterol esters, in cross sections through plaques.
Novel therapies for atherosclerosis could have a major global health benefits, given that cardiovascular disease is predicted to continue to be one of the leading causes of death. Joseph L. Witztum explained the role of low density lipoprotein (LDL) — the major component of bad cholesterol.
The second session focused on inflammation, in particular the roles of prostaglandins, leukotrienes and eicosanoids. Garret A. FitzGerald began his talk by explaining why cyclooxygenase inhibition may lead to cardiovascular problems. He followed this with his group's recent insight into how niacin evokes platelet COX1-dependent prostaglandin D2 formation. Joshua A. Boyce described how LTC4, LTD4 and LTE4, together known as the cysteinal leukotrienes, drive inflammation. He talked in particular about his team's recent work showing that LTE4 impacts lung inflammation in a mechanism that involves platelets and thromboxane A4.
Ageing is associated with an increased risk of many diseases, including diabetes and infection. Simin Nikbin Meydani explained the critical role that eicosanoids and sphingolipids play in age-associated dysregulation of immune and inflammatory responses. She also presented data from dietary interventions, prompting a discussion about dose and efficacy of supplementation with the lipid antioxidant vitamin E. M. Cameron Sullards, standing in for Alfred H. Merrill, discussed the growing evidence for the roles that sphingolipids play in diet and health and explained how lipidomic tools are helping to uncover more.
Peter Tontonoz explained why the liver X receptors (LXRs) are important in both lipid metabolism and inflammatory signalling – functions which make synthetic LXR agonists potentially attractive therapeutics. Continuing with the theme of LXRs, Christopher K. Glass presented results identifying particular cholesterol pathway lipids, in particular desmosterol, as key ligands of LXRs with anti-inflammatory effects.
It was felt that the cancer session most clearly demonstrated the growing impact that lipid systems are having on drug discovery. PI3K, which catalyses the production of the signalling lipid PI3P, is a central enzyme in a highly conserved pathway that is crucial for both cancer and insulin resistance. Lewis C. Cantley talked about the preclinical and clinical progress in the development of PI3K inhibitors as anticancer drugs. Julie D. Saba presented work by her team to characterize a new family of sphingolipids called sphingadienes. These may have the potential to treat colon cancer by acting on the same pathway as PI3K inhibitors, but through a different mechanism. Another important lipid pathway in cancer is the production of lysophosphatidic acid by the enzyme autotaxin. Gabor J. Tigyi described his team's quest for lysophosphatidic acid analogues that are effective autotaxin inhibitors. Next, Christian R.H. Raetz presented his group's recent discovery of the enzyme responsible for the production of cardiolipin, a mitochondrial lipid with a role in apoptosis. Finally, phospholipase D, whose aberrant expression is linked to cancer and other diseases, is another target for cancer therapies. H. Alex Brown presented his team's recent discovery of a group of phospholipase D inhibitors that act through a unique mechanism. This was revealed in part by a new type of click chemistry that combines affinity tags for lipid species with backscattering interferometry to obtain critical kinetic parameters of interfacial interactions.
The future of lipidomics
Lipidomics data is being produced fast — some would say faster than its impact can be thoroughly assessed. The question of how data should be stored and searched is being actively discussed. So too is the question of how lipidomics data can be integrated with data from the other “omics” fields. After all, the proteome and lipidome are artificial concepts not recognized by the cell, and merely reflect the different processes required to separate and analyze those species. The ability to accurately measure and integrate events occurring in the nucleus with changes in protein levels and production of key metabolites shows the realization of the promise of omic research. This will lead to a true systems level analysis of cells and complex organisms.
There were also other excellent talks and posters that we don't have space to describe. These came from a wide variety of disciplines, showing that the lipidomics field has been successful in attracting a broad range of life scientists.