Location: Obesity and Metabolism Research
Project Number: 2032-51530-025-007-N
Project Type: Non-Funded Cooperative Agreement
Start Date: Oct 2, 2017
End Date: Aug 30, 2022
Objective:
There is an unmet need to find reliable biomarker patterns that characterize the trajectory from health to cardiometabolic diseases. Several lines of evidences suggest that targeted lipidomic profiling of oxylipins (physiological and immunological oxygenated lipid mediators) could provide predictive biomarker patterns of the cardiometabolic syndrome while monitoring the efficacy of nutritional prevention of cardiometabolic diseases initiation and progression. The primary objective of this study is to evaluate combining nutritional status information with comprehensive and high throughput oxylipin profiling techniques as reliable early biomarkers of cardiometabolic dysfunction, and the response of these states to nutritional intervention.
Oxylipins are both biomarkers and mediators of oxidative stress and inflammation, two overreaching processes in the pathogenesis of the cardiometabolic syndrome (CardMetS). Oxylipins also have important homeostatic roles related to the cardiometabolic status. Oxylipins derived from different pathways as well as different substrate PUFAs can have similar or opposing effects which can be beneficial or detrimental. In addition, bioactives from dietary components including nuts, olive products, and red wine modulate the inflammatory mediator synthesis by impacting various enzyme and signaling pathways. Moreover, experimental studies based on impaired oxylipin metabolism involving polymorphism or using transgenic mouse models strongly support a causal link between oxylipin metabolism and cardiometabolic status, and several case-control and cross-sectional studies showed that individuals with altered cardiometabolic status (i.e., obesity, insulin-resistance, and vascular function alteration) have significant changes of their oxylipin profiles or metabolism. Therefore, both genetic and dietary factors may play a role in the alteration of oxylipin metabolism and a major objective of this project is to evaluate if concurrent assessment of nutritional factors will enhance the biomarker potential of circulating oxylipins in the assessment of cardiometabolic health.
Approach:
1. Provide an optimized and reliable method for the quantitative profiling of plasma oxylipins: The objective is to optimize the established method developed by collaborator-A in Hannover-Germany by enlarging the current oxylipin profile, performing tests of automatization for the rate-limiting steps, optimizing conditions of storage and preparation and performing method transfer and inter-lab validation, as well as data collection and analysis. Collaborator-B, ARS researcher in Davis, California, will consult on method development of the inter-lab validation. Collaborators-C in Paris, France will perform Inter-lab validation and set up the automatization tests on robots.
2. Identify candidate oxylipins by discriminating the dietary patterns, the cardiometabolic status and their ability to predict cardiometabolic syndrome (CardMetS) development: The objectives are to perform a cross-sectional analysis aiming to compare the oxylipin profiles of individuals with different quality dietary patterns with or without CardMetS and longitudinal analysis aiming to compare individuals at different stages of CardMetS development. The steps to identify candidate oxylipins include: using discriminant modelling, characterization of the candidate oxylipins include: A) correlation with dietary and clinical parameters; B) assessment of biological plausibility; and C) assessment of CardMetS prediction performance. Collaborators-D in Wroclaw, Poland will perform subject selection, plasma sample expedition, dietary score computation, metabolic syndrome assessment and data analyses. Collaborators-C will perform biostatistics/data analysis and interpretation. Collaborator-B, ARS researcher in Davis, California, will assist in biostatistics, data analysis and interpretation. Collaborator-A will profile oxylipin. Collaborators-E in Paris, France will perform biostatistics and data interpretation. Collaborators-F in Copenhagen, Denmark will share and manage data.
3. Validate the consistency of the identified oxylipins and assess their reliability and convenience to monitor dietary intervention efficacy: The objectives are to replicate the cross-sectional analyses in an independent cohort allowing validation of the identified oxylipins consistency and reproducibility, assess candidate oxylipins reliability and monitor the changes of CardMetS status in response to dietary intervention and conceptualize visualization tools to simplify the interpretation of the candidate oxylipins identified and validated. Subjects for this research will be selected from the French NutriNet-Santé cohort and the existing cohort biobanks from SHOPUS and iMAPS studies. Collaborators-E will perform subject selection, plasma sample expedition, dietary score computation, metabolic syndrome assessment, data analyses contribution and interpretation. Collaborators-C will profile oxylipin, manage data analysis. Collaborator-B, ARS researcher in Davis, California, will profile oxylipin of the iMAPS samples, and contribute to data analyses. Collaborators-F will manage data sharing, provide samples from the SHOPUS study and assist in data analyses and interpretation.
