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HDHL Biomarkers: Fatty Acid Metabolism - Interlinking Diet with Cardiometabolic Health (FAME)

Reference	BB/P028217/1
Principal Investigator / Supervisor	Professor Julie Lovegrove
Co-Investigators / Co-Supervisors	Professor Ian Givens, Dr Kim Jackson
Institution	University of Reading
Department	Food and Nutritional Sciences
Funding type	Research
Value (£)	124,799
Status	Completed
Type	Research Grant
Start date	01/08/2017
End date	31/07/2021
Duration	48 months

Abstract

The overall objective is to use existing biobanked samples and dietary and phenotype data from cohort studies and randomized controlled trials to: a) identify novel lipidomics biomarkers of cardiometabolic health which could replace or be used in addition to fatty acid profiles as more sensitive biomarkers of status and of future cardiometabolic clinical events, b) establish relationships between whole diets and specific foods with tissue status of fatty acids as explanatory factors for diet relationships with cardiometabolic health, and c) investigate genetic determinants of fatty acid status and metabolism which modify the physiological effects of dietary intake. WORKPLAN WP1. Lipid metabolites from lipidomics as novel biomarkers of cardiometabolic health will be identified based on follow-up of prospective studies on type 2 diabetes with exploration and cross-validation (EPIC-Potsdam cohort and CORDIOPREV trial). Potential for dietary modification of identified biomarkers will be tested in well-controlled trials involving FA modification (DIVAS, LIPGENE, RESET, SATGENE). WP2. Specific SFA and trans-FA and novel lipid biomarkers will be tested as biomarkers of dairy fat intake in a well-controlled trial (RESET) and subsequently evaluated as markers of cardiometabolic health (DIVAS, SATGENE, RESET) and long-term cardiometabolic risk (EPIC-Potsdam, CORDIOPREV, PREDIMED [n=7447]) WP3. Polyphenols and candidate genes as determinants of response to FA intake will be evaluated in the PREDIMED trial and EPIC-Potsdam cohort and subsequently validated in well-controlled trials on FA (LIPGENE, SATGENE) and polyphenol (FLAVURS) modification. EXPECTED RESULTS Results of the project may contribute to the refinement of current food and nutrients based dietary guidelines, e.g. with regard to dairy intake, PUFA intake and plant-based diets and the targeting of intervention strategies aimed at improved cardiometabolic health to those most likely to benefit

Summary

Dietary fatty acid composition is an important determinant of cardiometabolic health and risk of cardiometabolic diseases such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), but mechanisms underlying this relationship are still not entirely clear. This proposal will use existing biobanked samples and dietary and phenotype data from cohort studies and randomized controlled trials to a) identify novel lipidomics biomarkers of cardiometabolic health which could replace or be used in addition to fatty acid profiles as more sensitive biomarkers of status and of future cardiometabolic clinical events, b) establish relationships between whole diets and specific foods with tissue status of fatty acids as explanatory factors for diet relationships with cardiometabolic health, and c) to investigate genetic determinants of fatty acid status and metabolism which modify the physiological effects of dietary intake. The results from this multidisciplinary project will contribute to the evidence base for the refinement of current food and nutrient based dietary guidelines (in particular with regard to the intake of milk and dairy products, polyunsaturated fatty acids and plant-based diets), and the targeting of intervention strategies aimed at improved cardiometabolic health towards those most at risk of disease and/or be most responsive.

Impact Summary

Results of the project will help refine, current dietary guidelines and the targeting of interventions aimed at improved cardiometabolic health towards those most likely to be at risk of disease and/or be most responsive. a) The identification of novel biomarkers of cardiometabolic health and future risk of T2DM has strong potential for prediction of T2DM beyond classical risk factors (Floegel et al. 2013) and could therefore be incorporated into existing prediction models, e.g. the German Diabetes Risk Score developed at project partner DIfE (Mühlenbruch et al. 2014). More precise prediction algorithms allow the better targeting of monitoring programs and prevention interventions to those at risk. Given that the project also aims to evaluate the potential for modification of these novel markers by dietary interventions, the project will also provide the knowledge base to modify risk through dietary intervention with the aim to achieve long-term cardiometabolic health. b) In Europe between 17-41% of dietary SFA is derived from dairy products (Eilander et al. 2015). Given that the effect of high SFA intake on cardiometabolic intermediate biomarkers (lipids, blood pressure and insulin resistance) and cardiometabolic risk (T2DM, CVD) may be differential by distinct subgroups of SFA or their main food sources (dairy SFA associated with reduced cardiometabolic outcomes), it is a priority to establish the impact of dairy SFA on cardiometabolic health. c) Common gene variants which determine the response to PUFA intake and thus intake-health end-point associations may in the future be used to stratify dietary FA recommendations to individuals more likely to be responsive. d) Information on other dietary determinants of PUFA metabolism beyond FAs will be informative as it may provide, a) novel approaches to optimize tissue PUFA status, b) extent current knowledge regarding the molecular and physiological mechanisms underlying the cardio-metabolic benefits of a plant baseddiet, and c) contribute to the refinement of the current rather generic dietary recommendations for the intakes of plant based foods such as fruit and vegetables.

Committee	Not funded via Committee
Research Topics	Diet and Health
Research Priority	X – Research Priority information not available
Research Initiative	ERA-HDHL Biomarkers for Nutrition and Health [2016]
Funding Scheme	X – not Funded via a specific Funding Scheme

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