Coordinator  Dr. Dominique Langin INSERM Unité 317,  Institut Louis Bugnard, Faculté de Médecine, Hôpital Rangueil, Bâtiment L3,  31 403 Toulouse Cedex 4, France Tel: + 33 5 62172950 Fax: + 33 5 61331721 e-mail:langin@rangueil.inserm.fr

Toulouse  Dr. Max Lafontan INSERM Unité 317, Institut Louis Bugnard, Faculté de Médecine, Hôpital Rangueil, Bâtiment L3,  31 403 Toulouse Cedex 4, France Tel: + 33 5 62172950 Fax: + 33 5 61331721 e-mail:lafontan@rangueil.inserm.fr

Oxford Dr. Keith N. Frayn Oxford Lipid Metabolism Group, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE, UK Tel: +44 1865 224180  Fax: +44 1865 224652 e-mail keith.frayn@oxlip.ox.ac.uk

Huddinge  Dr. Peter Arner The Lipid Laboratory, Karolinska Institute at the Department of Medicine, Huddinge Hospital,  S-141 86 Huddinge, Sweden Tel : +46 8 58582342 Fax:  +46 8 58587223 e-mail: Peter.Arner@medhs.ki.se

Maastricht Prof. Wim Saris & Dr. Ellen Blaak  Department of Human Biology and Endocrinology, Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands Tel: + 31 43 3881639 Fax: + 31 43 3760976 e-mail:W.Saris@HB.UNIMAAS.NL

Lyon  Dr. Hubert Vidal & Prof. Martine Laville  INSERM Unit 449, Faculté de Médecine R. Laënnec,  69373 Lyon Cedex 08, France Tel: +33 478 77 86 29 Fax: +33 478 77 87 62 e-mail : vidal@laennec.univ-lyon1.fr

Madrid  Prof. Emilio Herrera Facultad de Ciencias Experimentales y Tecnicas, Universidad San Pablo-CEU,  Ctra. Boadilla del Monte km 5.3,  E-28668 Madrid, Spain Tel.: +34 1 3510550 Fax: +34 1 3510496 e-mail: e.herrera@ceu.es

Praha Prof. Vladimir Stich & Prof. Vojtech Hainer Department of Sport Medicine, 3rd Faculty of Medicine, Charles University, Ruska 87,  100 00 Praha 10, Czech Republic Tel: + 42 267102209 Fax: + 42 267102263  e-mail: Vladimir.Stich@lf3.cuni.cz

EC Scientific Officer Dr. Jürgen Lucas European Commission DG XII-B.I.1, Food, Health and Environment, SDME 8-32 Rue de la Loi 200 1049 Bruxelles, Belgium Tel: +32 2 296 41 52 Fax: +32  2 296 43 22 e-mail: jurgen.lucas@dg12.cec.be

Cardiovascular disease is a major health problem in Europe, causing 50% or more of all deaths at considerable cost to health services. Obesity is a growing problem in Europe, and as the population becomes more obese so an increase in obesity-related diseases, especially cardiovascular disease and type 2 diabetes mellitus, is to be expected. Therefore a better understanding of the origins and treatment of these common conditions must be important both in public health terms and in terms of advice to, or treatment of, the individual.

Both cardiovascular disease and obesity must represent the result of interactions between genetic and environmental factors. Both have increased rapidly in the present century, over a period when the gene pool in Europe is unlikely to have changed significantly. On the other hand, not all people develop these conditions despite many common environmental factors throughout Europe. A clear example is seen from the results of the Europe-wide MONICA study: death-rates from cardiovascular disease vary widely in different parts of Europe, even when adjusted for factors such as obesity.

The overall working hypothesis for FATLINK is that dietary fatty acids are an important mediator of the development of obesity and cardiovascular disease, and that a greater understanding of the effects of dietary fatty acids, in terms of their role in regulation of gene expression and their metabolic pathways in different tissues, will enable us to provide more soundly-based nutritional advice, to develop new pharmacological treatments for these diseases, and possibly to develop new foods with specific physiological functions aimed at combating the development of these conditions. In parallel, we propose that the effects of very-low-calorie diets and exercise programmes used for weight control may be understood as ‘negative dietary energy’, or removal of dietary fatty acids. Again, when the interaction of these treatments with gene expression is more clearly understood, it may be possible better to tailor these treatments to individuals likely to respond, and on a population level it may be possible to improve the prescription of such treatments.

The immediate objectives of this Concerted Action are therefore the following:

• To understand the regulation of gene expression in different tissues by dietary fatty acids, concentrating on genes likely to be involved in cardiovascular disease and insulin resistance
• To understand the early metabolism of dietary fatty acids in different tissues, how this differs between individuals, and how it depends on nutritional factors
• To understand the effects of dietary fatty acids on lipoprotein metabolism including oxidizability, and how this is modified by dietary anti-oxidants
• To understand the effects of ‘negative energy’ in the form of very-low-calorie diets and exercise programmes, in terms of the regulation of gene expression and fatty acid metabolism.

• To improve dietary advice on a population level to lessen the incidence of obesity, to aid weight control, and to reduce cardiovascular disease risk
• To improve dietary advice on an individual basis based on a clearer understanding of nutrient-gene interactions
• To improve the prescription of weight-reducing and controlling measures, such as very-low-calorie diets and exercise programmes, on both a population and an individual basis.

• To standardize clinical protocols and description of subjects, allowing comparison of data from different centres within FATLINK
• To develop the use of reverse transcription competitive polymerase chain reaction (RT-cPCR) technique to determine mRNA levels of multiple markers in human adipose tissue and muscle, and their response to nutritional manipulation.
• To improve methods for studying adipose tissue and skeletal muscle metabolic regulation in vivo

To extend the application of whole body and tissue substrate utilization and oxidation measured by means of tracer techniques
 
Dr. Dominique Langin