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Lipgene

Findings from the Lipgene Project:
Human Nutrition Studies

Insulin resistance (a muted blood glucose response to insulin) is a key characteristic of the metabolic syndrome. It has long been known that the composition of dietary fat influences this aspect of insulin function. Only now are we beginning to understand how common human genetic variation will interact with this.

I. SUVIMAX Study

Lipgene scientists have access to data from 13,000 participants in the SUVIMAX cohort. The SUVIMAX trial is an ongoing randomised, double-blind, placebo-controlled, primary prevention trial to evaluate the effect of daily antioxidant supplementation on the incidence of cancer and coronary heart disease. The participants have been tracked every two years for 8 years and full dietary, biochemical, clinical and genetic data are available.

To date, 877 subjects have developed the metabolic syndrome and scientists have selected 877 matched controls. DNA from each individual has been extracted and genotyped, focussing on specific areas of the genome that are of particular interest. Alongside this work, other scientists have completed the analysis of all subjects’ dietary records and have compared individual fatty acid intake with plasma fatty acid profiles. This will now lead onto the combined analyses of dietary, biochemical and genotypic data.
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II. Human Nutrition Dietary Intervention Study

Lipgene has conducted a human feeding intervention study in 8 cities across Europe to examine how variation in the composition of dietary fat influences the metabolic syndrome. From a total of over 12,000 subjects screened for the study, 223 individuals with the metabolic syndrome were selected and 219 completed the intervention, which assessed the effect of both dietary fat quantity and quality.

Such an intervention was a huge undertaking as the logistics of supplying specially designed products to 8 centres across Europe proved challenging. The dietary intervention has now been completed and all samples have been collected and analysed.

Smaller sub-studies are now underway looking at different aspects of post-prandial lipid metabolism using stable isotopes as well as NMR metabolomic profiling of blood and urine samples.
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III. Functional and Molecular Studies

This research is underway to investigate the role that dietary fatty acids play in the basic biology of the metabolic syndrome using animal and cell models. In summary:

  • Studies assessing the role of fatty acids as regulators of adipogenesis in a human cell line are still progressing well.
  • Work investigating fatty acids as molecular markers of adipogenesis is looking specifically at the role of fatty acids on gene expression in a human cell line. This year, scientists have identified a number of changes in gene expression occurring in these cell lines with different fatty acids.
  • Investigation of the role of fatty acids on human skeletal muscle cell fatty acid uptake, as well as skeletal muscle gene expression and signalling pathways related to glucose and lipid metabolism is progressing well.
  • Studies assessing the effects of dietary fatty acids on adipose tissue in animal models are also progressing well. A feeding study has been completed and scientists have demonstrated a reduction in the size of fat depots when a specific fatty acid called TTA (tetradecylthioacetic acid) was fed.
  • Work is still underway to assess the effects of omega-3 fatty acids on the clinical consequences of insulin resistance.

Overall, these studies link dietary fat with different cell and animal models to cover all of the main areas of metabolic perturbation associated with obesity and the metabolic syndrome. The work involves adipogenesis, inflammation, vascular function, hypertension, insulin resistance and glucose metabolism.

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Dropper, Agar plate
Findings from the Lipgene Project