Untargeted Profiling of Bile Acids and Lysophospholipids Identifies the Lipid Signature Associated with Glycemic Outcome in an Obese Non-Diabetic Clinical Cohort.

Nicolas Christinat,Mojgan Masoodi,Armand Valsesia

doi:10.3390/biom10071049

Nicolas Christinat, Mojgan Masoodi + Show 1 more

Open Access

https://doi.org/10.3390/biom10071049

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Journal: Biomolecules	Publication Date: Jul 15, 2020
Citations: 8	License type: CC BY 4.0

Affiliation: Nestlé (Switzerland), University Hospital of Bern

Abstract

The development of high throughput assays for assessing lipid metabolism in metabolic disorders, especially in diabetes research, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH), provides a reliable tool for identifying and characterizing potential biomarkers in human plasma for early diagnosis or prognosis of the disease and/or responses to a specific treatment. Predicting the outcome of weight loss or weight management programs is a challenging yet important aspect of such a program’s success. The characterization of potential biomarkers of metabolic disorders, such as lysophospholipids and bile acids, in large human clinical cohorts could provide a useful tool for successful predictions. In this study, we validated an LC-MS method combining the targeted and untargeted detection of these lipid species. Its potential for biomarker discovery was demonstrated in a well-characterized overweight/obese cohort subjected to a low-caloric diet intervention, followed by a weight maintenance phase. Relevant markers predicting successful responses to the low-caloric diet intervention for both weight loss and glycemic control improvements were identified. The response to a controlled weight loss intervention could be best predicted using the baseline concentration of three lysophospholipids (PC(22:4/0:0), PE(17:1/0:0), and PC(22:5/0:0)). Insulin resistance on the other hand could be best predicted using clinical parameters and levels of circulating lysophospholipids and bile acids. Our approach provides a robust tool not only for research purposes, but also for clinical practice, as well as designing new clinical interventions or assessing responses to specific treatment. Considering this, it presents a step toward personalized medicine.

Highlights

Lipidomics has become an increasingly important tool in metabolic disorders and diabetes research for the detection of biomarkers in human plasma for early diagnosis or prognosis of the prediabetic state
Good chromatographic separation of the different bile acid isomers is critical for their accurate quantification by mass spectrometry
A water-methanol system containing an acetic acid/ammonium acetate buffer was chosen as the eluent, as it is known to be well-suited to the LC-MS quantification of bile acids [16]

Summary

Introduction

Lipidomics has become an increasingly important tool in metabolic disorders and diabetes research for the detection of biomarkers in human plasma for early diagnosis or prognosis of the prediabetic state. Lysophosphospholipids (LPL) have been detected as potential markers for identifying prediabetic patients. An association between lower levels of circulating LPC(16:0), LPC(16:1), LPC(18:2), and LPC(20:0) and obesity, insulin resistance, and type 2 diabetes has been reported [1,2,3] These lipid species are mainly formed from phospholipids upon the activation of phospholipases A1 and A2. They can act as signaling lipids and exhibit a wide range of biological effects. Their roles in the regulation of inflammation [4,5] and activation of the transcription factor peroxisome proliferator-activated receptor (PPAR)δ have been reported [6]

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