Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Final Report Summary - LIPGEN (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis)

There are many statistical benchmarks against which to measure the global crisis in obesity - its prevalence, its growth, its impact on co-morbidities such as diabetes and hypertension and its economic and social consequences. In terms of addressing this, most serious public health nutrition crisis, there are three complementary strategies. The first and the one which must receive the greatest investment is the prevention of new cases of over-weight and then of obesity. The second must involve the treatment of overweight and obesity through both physical activity and through diet. The third strand is the need to develop both physical activity and dietary strategies to manage the adverse effects of excess body fat among those who are over-weight and obese. The latter was at the heart of the LIPGENE project.

At the time of planning, the project there was an extensive literature with animal models to suggest that the level and composition of dietary fat could significantly influence insulin regulation of glucose metabolism such that the diabetes of obesity could be remedied. One study in humans appeared to support that hypothesis. This study, known as the Kanwu study, recruited individuals with a constellation of symptoms associated with obesity, collectively known as the metabolic syndrome and found some evidence that modification of dietary fat intake significantly influenced insulin resistance in humans. Against that background, the LIPGENE project began to be designed.

The core of the LIPGENE project was a human nutrition intervention study which would build on the Kanwu study but take the research further in:
(a) extending the range of dietary intervention;
(b) increasing the size of the study population;
(c) extending the duration of dietary intervention; and
(d) introducing newer and more exacting end point measures of the impact of dietary intervention.
Whereas a dietary intervention study can definitively establish the effects of dietary fat on the metabolic syndrome, it has some but limited potential to establish any significant associations between natural variation in gene sequence (genotype) in a population with any diet-induced tendency toward the metabolic syndrome. To address that issue, LIPGENE were very fortunate to have access to the SUVIMAX cohort which followed 14 000 French adults over 8 years recording detailed dietary, clinical and biochemical parameters every 2 years. Thus, LIPGENE was able to identify 877 subjects who over the 8 years or so developed the metabolic syndrome and an age- and sex-matched group who remained free of the metabolic syndrome for the duration of the prospective study. Finally, a series of animal and cell models were initiated to probe more deeply into the basic biological mechanisms linking dietary fatty acids, genes and the metabolic syndrome.

Both dietary analysis and blood biochemistry confirmed that the dietary intervention was successful in modelling lipid profiles along the intended directions. Although the two low-fat diets were intended to be isocaloric, there was a significant weight loss in both groups to a level of about 0.8 kg. Overall, the dietary fat intervention led to little change in insulin sensitivity. However, the response was influenced by habitual fat intake. For example, in individuals with habitual fat intakes below 36 % of energy, particularly females, insulin sensitivity was improved on the high fat, high MUFA diet. All in all, this finding is of major importance in human nutrition for it shows that, unlike animal models, humans are much less sensitive to changes in dietary fat intake with regard to insulin sensitivity.

Besides these two main studies, a number of sub-studies in nutrition were conducted. Several centres participated in a series of studies which set out to probe deeper into the relation of lipids to insulin function. One of the most exciting areas of the study in this regard was related to the novel fatty acid: tetra-decylthio-acetic Acid (TTA). This dramatically reduced body fat in rats without influencing food intake. It appears that the liver engages in a highly up-regulated oxidation of absorbed dietary lipids. Two other studies in nutrition involved human studies and both focussed on the volunteers in the human intervention study when subjects were fully adapted to the altered dietary fat intake at week 12. In one case, subjects were studied in the post-prandial phase following a high-fat meal. Several key regulatory pathways were observed to change in different directions after the fat load according to long term dietary intake. Thus, further studies should consider the use of the post-prandial phase to study the long term effects of dietary fat on insulin function. In another study, stable isotopes were used to explore energy metabolism in skeletal muscle. This study found that despite the impact of dietary lipid intervention, no effect on skeletal muscle handling of lipids was seen, which is consistent with the findings of the human intervention study which found no effect of dietary lipids on insulin functions in humans.

A demonstration work package successfully developed potentially commercially viable food prototypes that had modified lipid profiles relevant to the metabolic syndrome and acceptable sensory characteristics and functional performance. In total, five food products were developed, a poultry meat enriched with EPA and DHA; dairy food (milk and cheese) with reduced saturated fatty acid and enhanced monounsaturated fatty acid content; two spreads (one 25 % fat spread with 500 mg EPA and DHA per 20 g serving, and one 25 % fat spread with 2 g ALNA per 20 g serving) and a salad oil with 2 g ALNA and 500 g EPA and DHA per 14 g serving. The impact of replacing regular foods with these enriched food prototypes on population intakes of omega-3 PUFAs was also estimated using dietary data from the United Kingdom, the Netherlands and France. As may be expected, it was shown that the availability of food enriched with ALNA, EPA and DHA could help people achieve optimal omega-3 PUFA intakes; however the type of food enriched must be common, everyday foods.

Finally, an online consumer study was conducted to evaluate promising communication routes on the metabolic syndrome and the enriched food prototypes. Results showed that communicating metabolic syndrome of these prototype foods is not something consumers reject but rather a preferred communication message.

LIPGENE demonstrated a consumer acceptable approach to enhance dietary intakes of omega-3 fatty acids, by modifying common foods such as spreads and salad oils, dairy and poultry using advances in agro-food technology.

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