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

Lead Research Organisation: University of Reading
Department Name: Food and Nutritional Sciences

Abstract

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.

Technical Summary

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

Planned Impact

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.

Publications

10 25 50
 
Description Collaboration with co-applicant (Professor Anne-Marie Minihane) within the Nutrigenetics Group at Norwich Medical School, University of East Anglia (UEA) 
Organisation University of East Anglia
Department Norwich Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution Dietary intervention studies from the Hugh Sinclair Unit of Human Nutrition (RESET, DIVAS, LIPGENE, SATgene, FLAVURS) will be used for detailed plasma phospholipid fatty acid and lipidomics analyses, along with genotyping.
Collaborator Contribution The research focus is investigating the independent and interactive impact of select dietary components (in particular n-3 FAs and flavonoids) and common gene variants on cardiometabolic health, including insulin sensitivity, vascular health and liver fat. Much of the research (including SATgene, FLAVURS and CIRCLES) uses human intervention trial methodologies, but a variety of wild-type and transgenic rodent models and cell and molecular techniques to investigate underlying physiological and molecular mechanisms inform the foci of our RCTs. Genotyping approaches include targeted SNP analysis along with whole gene or exon sequencing.
Impact no outcome yet.
Start Year 2017
 
Description Collaboration with the Department of Molecular Epidemiology at the German Institute of Human Nutrition (DIfE) (Professor Matthias Schultze) 
Organisation Leibniz Association
Department German Institute of Human Nutrition (DIfE)
Country Germany 
Sector Public 
PI Contribution Dietary intervention studies from the Hugh Sinclair Unit of Human Nutrition (RESET, DIVAS, LIPGENE, SATgene, FLAVURS) will be used for detailed plasma phospholipid fatty acid and lipidomics analyses, along with genotyping.
Collaborator Contribution The Department of Molecular Epidemiology at the German Institute of Human Nutrition (DIfE), led by Matthias Schulze, has long-standing experience in epidemiologic research on dietary determinants of T2DM risk based on large-scale population-based studies, in particular the EPICPotsdam cohort study. The research has specifically focused on FA biomarkers of intake and metabolism (phospholipid composition, lipidomics) and their relation to T2DM, also in the context of genetic interactions. The group has substantial experience in complex statistical modelling, e.g. with regard to biomarker mediation effects and dietary pattern analysis. Also, FA profiling of PREDIMED, FLAVURS and CIRCLES samples will be carried out by the group as part of the FAME project.
Impact no output yet.
Start Year 2017
 
Description Collaboration with the Department of Preventive Medicine & Public Health at the University of Navarra (UoN)-Professor Miguel Martinez-Gonzales & Dr Cristina Razquin Burillo) 
Organisation University of Navarra
Department Department of Preventive Medicine and Public Health
Country Spain 
Sector Academic/University 
PI Contribution Dietary intervention studies from the Hugh Sinclair Unit of Human Nutrition (RESET, DIVAS, LIPGENE, SATgene, FLAVURS) will be used for detailed plasma phospholipid fatty acid and lipidomics analyses, along with genotyping.
Collaborator Contribution In the frame of PREDIMED trial, we are studying lipidomics profilings and their relationship with CVD and the potential effect of the MedDiet in changing these profiles as a mediator for changing CVD risk (NIH funded project). FA profiling and potential genetic interactions will be determined to give a better understanding of the biological mechanisms involved in the beneficial effects observed with the MedDiet and CVD.
Impact no output yet.
Start Year 2017
 
Description A talk or presentation - Hugh Sinclair Nutrition Research Symposium 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Laury Sellem, PhD student, presented the protocol for the FAME project in University of Reading.
Year(s) Of Engagement Activity 2018
 
Description FAME Consortium Meeting in Cordoba, Spain "Progress to date on WP2 - FAME" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact This presentation aimed to discuss the progress of the FAME Consortium with all collaborators and to define the next steps and schedule.
Year(s) Of Engagement Activity 2018
 
Description FAME Consortium meeting in Cordoba, Spain "Progress of Fatty Acid Determination for WP2 - FAME" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact This presentation aimed to discuss the progress of the FAME Consortium with all collaborators and to define the next steps and schedule.
Year(s) Of Engagement Activity 2018