Staff PhD

In vitro studies on metabonomic responses to fatty acids

Heidi Najbjerg

Background

It is known that a high intake of saturated fatty acids increases the risk markers of cardio-vascular diseases (CVD). In contrast, intake of unsaturated fatty acids (MUFA, PUFA, and n-6 PUFA) has been found to reduce total and LDL cholesterol levels. However, the relations are very complex as both chain length of the fatty acids, degree of unsaturation and cis/trans configuration seem to play a role for the action of the fatty acids in relation to effects on important health indicators. The molecular mechanisms triggering these effects are poorly understood. However, it has been shown that the fatty acid composition of cow milk can be manipulated through feeding strategies. This implies possibilities for making healthier diary products if it is understood how various fatty acids and mixtures of fatty acids act on health.

Aim

The aim of the project is to elucidate how various fatty acids act on cellular metabolism, the cellular response to the exposure of various fatty acids and mixtures of fatty acids using metabonomic techniques in combination with in vitro models. An insight into the mode of action of various fatty acids on the cellular level will give us a better understanding of the significance of dietary fatty acid composition on the risk of developing diet-related diseases and thereby provide crucial information required for the formulation and development of healthier foods.

It is hypothesized that some fatty acids may interact directly or through metabolized products and have impact on important factors such as adipocyte proliferation and insulin sensitivity, and that this is reflected at both the genomic, proteomic and metabonomic level.

Research Outline

Metabonomics will be applied to elucidate the global metabolic response to various fatty acids and mixtures of fatty acids in cellular systems. The fatty acids will be chosen based on their known effects on CVD and diabetes in human studies, and include saturated fatty acid (SFA) C16 (negative risk factor), SFA C18 (neutral), MUFA’s with different chain length and PUFA’s (n-3 and n-6). The fatty acids will administered to liver cells in serum-free cultures, and the metabonomic profiles will be analyzed using proton NMR-based and GC-based metabonomics to establish potential biomarkers showing differential behaviour. The significance of the biomarkers will be evaluated in order to conclude on the fatty acid-disease relations. The present Ph.D. project is part of the project “Fatty acids in food and milk products: A nutriomics approach to establish biomarkers for health risks on the gene, proteome, and metabolite levels” funded by “Direktoratet for FødevareErhverv” (Project leader Jan Enghild, iNANO).