Part II: Lipidomics—A New Perspective to Explore the Mysteries of Life

At present, the main contents of lipidomics research include analysis and identification of lipids and their metabolites, lipid function and metabolism regulation (including key genes/proteins/enzymes), lipid metabolism pathways and networks. In particular, it is expected to make breakthroughs in lipidomics research in the coming years.

a. Large-scale, high-precision analysis to identify fluid lipid metabolites and their relationship to important diseases.

b. The relationship between dynamic changes of cells and their regional lipid groups and abnormal cellular functions;

c. The relationship between metabolic regulation of cholesterol and its oxidative modification processing and related metabolic diseases.

d. The relationship between metabolic regulation of fatty acids and related metabolic diseases.

e. The relationship between the lipid group and its metabolic regulation and the essential membrane structure necessary for life.

f. The basis for the development of lipid metabolites and their metabolic pathways and related drugs.

The establishment of extraction and separation standards, software development and in-depth research on databases, metabolic pathways and networks, and the establishment and improvement of related bioinformatics technology systems are three urgent issues that need to be addressed.

Many mathematical models are applied to the biochemical analysis of lipidomics and metabolomics, but there are still great challenges for us in qualitative and quantitative metabolites. In recent years, a unique patented "widely targeted metabolomics" technology has emerged, integrating a new metabolome detection technology that combines the advantages of nontargeted metabolomics and targeted metabolomics detection technologies to achieve high throughput, high sensitivity, and wide coverage targeted metabolomics detection. A qualitative and quantitative detection of 600+ metabolites in biological samples can find more compounds, and is easier to find biomarker. It covers more than 95% pathway in KEGG, which makes it easier for functional research. Some researchers have applied this technology to lipidomics and developed "wide-targeted lipidomics", which can stably detect thousands of lipids at one time, providing new insights into the important functions of lipids on the body.

Tumor Pathogenesis Analysis by Lipidomics

In a new study, researchers from Purdue University, Northwestern University, and Indiana University found that a metabolic trait is critical to the proper functioning of "cancer stem cells" that initiate tumor formation. They use a chemical to inhibit the activity of fatty acid desaturase, reducing fatality and the "stemness" of these cells, while effectively removing ovarian cancer stem cells and blocking spheroid formation in laboratory cultures and tumor initiation in laboratory mice. (published online on December 29, 2016, Cell Stem Cell)

Team of Yiqi Xu and Boliang Li from the Institute for Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences of CAS recently found that the inhibition of cholesterol esterification could enhance the anti-tumor activity of CD8+ T cells (also known as killer T cells).

Researchers found that the inhibition of cholesterol esterase ACAT1 could increase cholesterol levels on the plasma membrane, thus promoting T cell signal transduction and killing process. Avasimibe, a small molecule inhibitor of ACAT1, has been used to treat cancer in tumor-model mice and has shown good anti-tumor effects. The combined use of avasamab and an anti-PD-1 antibody as an immunological checkpoint blocking drug showed better anti-tumor effects. This research pioneered a new field of cancer immunotherapy and identified ACAT1 as a promising drug target.

Despite the challenges, researchers are still convinced that by analyzing certain metabolites and looking for biomarkers for disease, new methods will be provided for disease diagnosis.

Prime Jones is a senior researcher from MtoZ Biolabs. She is specialized in the field of proteomics study.