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Nutrient-gene interactions in human obesity:
Implications for dietary guidelines
NUGENOB

Contract number : QLK1-2000-00618
Contract type : Shared Cost Project
Total cost : € 4.011.639
EC contribution : € 3.208.844
Starting date : 1/02/2001
Duration : 36 Months
Scientific Officer : Barend Verachtert
Project website :
http://www.nugenob.com/
Coordinator
Dr Thorkild I.A. Sorensen
Copenhagen Hospital Corporation
Institute of Preventive Medicine
H:S Kommunehospitalet
Øster Farimagsgade 3-5
1399 Copenhagen K
Denmark
Tel.: +4533383860
Fax: +4533324240
E-mail: tias @ ipm.hosp.dk
Background

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 (i.e. fat intake) and genetic variations and functions in obesity. Seven hundred and fifty obese and 150 reference subjects will be examined by 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 hypocaloric dietary intervention (~ 600 kcal energy deficit per day), either with a low fat content (20-25% fat) or with a high fat content (40-45% 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.

Objectives

The overall objective of the project is to elucidate the role in human obesity of interactions between macronutrient composition of the diet with particular emphasis on fat intake and specific genetic variants. It aims at combining clinical/physiological variables to the effects of a very high-fat test meal challenge and a long-term hypoenergetic low-fat or hypoenergetic high-fat diet with knowledge of genetic make up and expression levels of individual genes.

This objective can be divided into the following specific aims:

  • Identification and characterisation of novel nutrient-sensitive candidate genes for obesity, i.e. genes in which variants result in differential responses in obesity-related physiological functions and in adipose tissue to nutrient challenges such as a high-fat meal and a long-term hypoenergetic alteration of dietary fat content.
  • Assessment of the effects of the variants and combinations of variants in known and novel nutrient-sensitive genes on the response in obese subjects to a high-fat test meal in the physiological functions: appetite and satiety, energy expenditure and nutrient partitioning, and circulating obesity-related substrates, hormones and metabolites.
  • Assessment of the combined effects the variants of novel and known nutrient-sensitive genes and a short- and long-term alterations in dietary fat content on the differential expression of selected functional genes in adipose tissue.
  • Identification of predictors of the changes in body weight and composition of obese subjects during a long-term hypoenergetic low-fat or high-fat dietary intervention programme. These predictors may be: a) variants or combinations of variants of the nutrient-sensitive genes, b) the obesity-related life style factors, c) the differential physiological functions observed at the test meal challenge, d) the gene expression in adipose tissue, or e) gene-phenotype or gene-environment interactions based on combinations of these predictors.
(expected) Results and achievements

This project is expected to increase in our understanding of the interaction between dietary fat and the genetic predisposition to obesity. This new knowledge will improve in several ways the basis for the ability to limit the development of the epidemic of obesity by more effective and more precisely targeted prevention and treatment.

More specifically, the expectation is to achieve more precise knowledge about, and improved understanding of:

  • Genomic position and structure, functional variants, and regulation of several novel nutrient-sensitive genes that may be involved in the pathogenesis of obesity.
  • The specific mechanisms underlying the well documented genetic predisposition to obesity, which is polygenic and probably heterogeneous with different genes playing a major role in different subsets of obese subjects.
  • Genes actively involved in the regulation of metabolic efficiency, in excessive accumulation of fat in adipose tissue and in the changes in fat content of the adipose tissue induced by alterations of the dietary fat content.
  • The complex role of fat intake in the pathogenesis of obesity by disclosing the specific nutrient-gene interactions both at a challenge of a single high-fat meal and during a long-term low-fat or high-fat dietary intervention.
  • The inter-individual variation in the response to a fat challenge by evaluating the physiological responses to a high-fat test meal in relation to the specific genotypes of the obese subjects, which will characterise the obese subjects with regard to their ability to metabolise fat.
  • The inter-individual variation in the changes in body weight and composition during a long-term hypoenergetic low-fat or high-fat dietary intervention.

It is envisaged that the results of this project may lay the grounds for:

  • Development of a new obesity taxonomy, in which new modes of classification of subtypes of obesity are based upon their specific genotypes, and the nutrient-gene interaction emerging during the high-fat test meal or the hypoenergetic low-fat or high-fat dietary intervention programme.
  • Development of diagnostic tools - on the basis of the genotyping and the responses to the challenge to a high-fat meal - that can discriminate obese subjects with respect to effectiveness of a long-term hypoenergetic low-fat or high-fat dietary intervention allowing accurate targeting of this intervention and delineation of obese subjects in whom other means of intervention are needed.

Partners

The Royal Veterinary and Agricultural University
Research Department of Human Nutrition
Rolighedsvej 30
1958 Frederiksberg C
Denmark
Steno Diabetes Center
Niels Steensens Vej 2
2820 Gentofte
Denmark
Department of Human Genetics, Institute of Biology
CNRS 8090, Institut Pasteur de Lille
1 rue Calmette
59000 Lille
France
Maastricht University
Centre NUTRIM
Dept. of Human Biology, Nutrition Research
PO Box 616
6200 MD Maastricht
The Netherlands
Huddinge Hospital
Lipid Laboratory
Department of Medicine
Karolinska Institute
Huddinge Hospital
141 86 Huddinge
Sweden
Huddinge Hospital
Obesity Unit
Department of Medicine
Karolinska Institute
Huddinge Hospital
141 86 Huddinge
Sweden
University of Nottingham
School of Biomedical Sciences
Queen's Medical Centre
Clifton Boulevard
NG7 2UH Nottingham
United Kingdom
Charles University
Third Faculty of Medicine
Department of Sports Medicine
Center of Preventive Medicine
Ruska 87
100 00 Praha 10
Czech Republic
UFR Broussais-Hôtel-Dieu
Université Paris VI
Department of Nutrition
1, Place du Parvis Notre-Dame
75181 Paris Cedex 04
France
INSERM
U317, Louis Bugnard Institute
Bâtiment L3
CHU Rangueil
31403 Toulouse Cedex 4
France
Dpto. Fisiología y Nutrición
Universidad de Navarra
C/. Irunlarrea s/n.
31008 - Pamplona (Navarra)
Spain


Fifth Framework Programme

PDF Version

:

Volume 1 (PDF 2.9 MB)

   

Volume 2 (PDF 1.9 MB)

 

Last update

:

23-09-2003



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