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Nutrient-gene interactions in human obesity: implications for dietary guidelines

Objective

An epidemic of obesity afflicts European populations, posing a major public health challenge due to the associated severe problems and inability to manage them. The project aims at improving understanding of interaction between nutrition (befit intake) and genetic variations. Six hundred obese and 120 reference subjects are invited to a scrutiny of dietary habits and relevant life style aspects, a 3-day dietary standardisation at 37% of energy as fat, a 1-day clinical investigation with a test meal with 60% fat, and a 10-week hypo caloric dietary intervention with 20-25% fat. Metabolic and hormonal responses to the test meal, changes during the intervention period in body weight and composition, and in gene expression in adipose tissue will be related to genotypes of selected new candidate genes. Such knowledge may improve treatment and prevention of obesity.
Overall outcome: Outcomes in terms of core publications focussing on:
-Postprandial response to the high fat test meal
-Weight loss on low vs. medium fat diet
- Metabolic, anthropometrical and life style related predictors of weight loss and predictors of differential response to low and moderate fat intake
- Identification of candidate genes and candidate gene variants
- Genotyping of the whole study population for a large number of gene variants in candidate genes
- Quantitative gene expression in adipose tissue, effect of hypo energetic diet intervention with low or medium fat intake
- Gene expression profiling in adipose tissue, effect of hypo energetic diet intervention with low or medium fat intake
- Identification of novel candidate genes or gene variants for obesity
- Integrating the results on phenotypic characteristics with genotyping and gene expression data Specific outcomes for further exploitation: Randomised, multi-centre trial of two hypo energetic diets with different fat content in obese subjects.

NUGENOB The possible differences in the response to low and medium fat diet are addressed. These results can provide the basis for future standard recommendations for dietary intervention regimes in the treatment of obesity. Predictors of weight loss and body composition changes A large panel of putative predictors are being tested for their association with weight loss success. The findings will improve the ability to predict which subjects will in general be successful in losing weight, and which diet will be optimal for certain subgroups of subjects. Identifying the specific mechanisms underlying the well documented role of genetic factors in response to dietary weight loss intervention By combining data on weight loss with data on genotype data we hope identify specific gene variants affecting the overall weight loss success and showing an interaction with diet. Genotyping may in the future serve as a diagnostic tool in obesity and for optimising treatment. The NUGENOB Biobank Serum and plasma samples taken in the fasting state, and following a high-fat test, plus samples taken following weight loss intervention (obese subjects), DNA from the whole study population, mRNA from abdominal SC adipose tissue obtained in fasting before and after dietary intervention in obese subjects.

The NUGENOB Databank Including more than 1100 variables describing the subjects in terms of background information, baseline subject characteristics, response to the high fat test meal, and response to the two weight loss interventions, genotyping and gene expression. Standard Operation Procedures The SOPs cover procedures related to clinical research in general and specifically to clinical investigation and dietary intervention in obese subjects. Candidate genes and gene variants for obesity Genes and gene variants with a putative role in obesity have been identified by linkage analyses, genome wide scan, association studies, by studying changes in gene expression in adipose tissue in response to energy restriction and varying fat content of the diet, and finally by bioinformatics search. Changes in gene expression in response to energy restriction with medium or low fat content Changes in gene expression in SC abdominal adipose tissue in response to energy restricted diet with moderate or low fat content was examined in sub-samples of the NUGENOB study population. Quantitative gene expression as well as gene expression profiling was conducted. Interactive database on nutrient-gene interaction in obesity Many studies pertaining to human as well as animals have addressed this topic, identifying genes for which the expression changes in response to energy restriction or change in diet composition. Members of the nugenob consortium has therefore initiated the making of a database on genes for which there is a known nutrient-gene interaction and a putative role in obesity. “Nutrient-gene interactions in the control of obesity” Verdich c, Clement K, Sorensen TIA for the books “Functional foods: ageing and degenerative disease” and “Food, diet and obesity” book chapter in Press at Woodhead Publishing The current knowledge on the role of genetic and environmental factors and nutrient –gene interaction in human obesity has been summarized in this book chapter. Communication of the knowledge gained form NUGENOB and background knowledge on the role of genetic factors and nutrient – gene interaction in obesity to European Consumers, Health Care Professionals and the industry. Within two to three years after the completion of the NUGENOB project, the project consortium will explore the options for funding of booklets to the consumers, health care professionals and the industry.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

BISPEBJERG HOSPITAL
Address
Kommunehospitalet, Oester Farimagsgade 3-5
1399 Koebenhavn K/copenhaegen
Denmark

Participants (10)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
1,Rue Du Professeur Calmette 1
59019 Lille
CHARLES UNIVERSITY PRAGUE
Czechia
Address
Ruske 87
100 00 Praha 10
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Address
Avenue Jean Poulhès
31403 Toulouse
KAROLINSKA INSTITUTE
Sweden
Address
Karolinska Hospital
17 176 Solna
NOVO-NORDISK A/S
Denmark
Address
Niels Steensens Vej 2
2820 Gentoffe
THE ROYAL VETERINARY AND AGRICULTURAL UNIVERSITY
Denmark
Address
Rolighedsvej 30
1958 Frederisksberg
UNIVERSIDAD DE NAVARRA
Spain
Address
Calle Irunlarrea S/n
31008 Pamplona
UNIVERSITE PIERRE ET MARIE CURIE - PARIS VI
France
Address
1, Place Du Parvis De Notre-dame
75181 Paris
UNIVERSITY OF MAASTRICHT
Netherlands
Address
Universiteitssingel, 40
6229 ER Maastricht
UNIVERSITÉ DE LILLE II
France
Address
1 Rue Du Professeure Calmette
59019 Lille