Defining Boundaries of Lipidomic Variations in Human Cohorts Federico Torta (Presenter) National University of Singapore Presenter Bio: My area of expertise covers structural biology, proteomics and lipidomics. I hold a PhD in Molecular Biology and Pathology and became a Research Assistant Professor at NUS in 2016. My main interest has always been in basic research but more recently I have been increasingly involved in translational and clinical research in large cohorts, especially in the field of metabolic diseases. My research interests lie at the intersection between lipids and proteins and in developing new analytical methodologies in the field, such as Native Mass Spectrometry, a powerful tool that can be used to study molecular complexes in native conditions.

Authors: Federico Torta, Sock Hwee Tan, Peter Benke, Bo Burla, Wai Ling Koh, Hyung Won Choi, Mark Chan, Markus R Wenk
National University of Singapore, Singapore

Advances in mass spectrometry-based lipidomics have greatly expanded our understanding of the extent and complexity of lipid dysregulation in disease conditions. Targeted lipidomics enables the sensitive measurement of several hundred individual lipid species in thousands of samples for each study. We present here population-based studies aimed at clarifying the variation of plasma lipid concentrations in healthy individuals and in patients affected by metabolic disorders, in both cross-sectional and longitudinal studies.

Introduction

Many lipids have been linked to pathological processes. Advances in mass spectrometry-based lipidomics have greatly expanded our understanding of the extent and complexity of lipid dysregulation in disease conditions. This technology enables the measurement of several hundred individual lipid species in thousands of samples for each study. Lipidomics in population-based studies has helped to clarify that concentrations of specific lipids are altered in several disorders and may serve as prognostic and diagnostic markers. To this extent, it is important to define the variation of plasma lipid concentrations in healthy as well as in sick individuals. Databases generated from these studies will provide a resource for the identification of novel biomarkers and for the discovery of potential drug targets.

Methods

Lipid extracts from human plasma, spiked with a mix of internal standards, were analysed by targeted LC-MSMS in MRM mode,utilising a 1290 Agilent UHPLC equipped with a C18 RP column and interfaced with a 6495 Agilent QQQ mass spectrometer. Data were analysed with MassHunter Quant software and corrected based on the behaviour of QC samples interspersed during the analytical runs. Representation of the data and statistical analysis were performed using in house R scripts.

Results

A cross-sectional study on healthy individuals revealed a variation of lipid species levels, in particular for ether phospholipids and phosphorylated sphingolipids, associated to the different ethnicity of the participants. Longitudinal studies on a different cohort allowed us to measure the intervals of lipid variations at different time scales. Larger groups of non-healthy individuals revealed new links between lipid levels and metabolic phenotypes.

Conclusions & Discussion

Collectively, our studies provide a controlled reference of plasma lipid

variations in characterized cohorts of healthy and non-healthy humans of Asian origin. Our results suggest that ethnic differences associate with plasma lipid species. The identified association of lipid levels with clinical factors presented in this study could contribute to

translational research by triggering further exploration of the underlying biological mechanisms that could lead to targeted therapies and preventative measures.

Sphingolipid Analysis in Clinical Research. Burla B, Muralidharan S, Wenk MR, Torta F. Methods Mol Biol. 2018;1730:135-162.

Sphingolipidomics analysis of large clinical cohorts. Part 1: Technical notes and practical considerations. Chew WS, Seow WL, Chong JR, Lai MKP, Torta F, Wenk MR, Herr DR. Biochem Biophys Res Commun. 2018 Apr 18. pii: S0006-291X(18)30845-3

Lipidomic profiling of plasma in a healthy Singaporean population to

identify ethnic specific differences in lipid levels and associations with disease risk factors. Husna Beguma, Federico Torta, Pradeep Narayanaswamyc, Piyushkumar A. Mundraa, Shanshan Ji, Anne K. Bendt, Woei-Yuh Saw, Yik Ying Teo, Richie Soong, Peter F. Little,

Peter J. Meikle, Markus R. Wenk. Clinical Mass Spectrometry 6 (2017) 25–31