Award details

Role of fatty acid chain length in energy balance and adaptive thermogenesis

Reference	BB/H002731/1
Principal Investigator / Supervisor	Professor Antonio Vidal-Puig
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Clinical Biochemistry
Funding type	Research
Value (£)	513,407
Status	Completed
Type	Research Grant
Start date	01/10/2009
End date	30/09/2012
Duration	36 months

Abstract

A fundamental question regarding the fate of cellular lipids, in particular free fatty acids, is how these lipids are targeted to various fates, either oxidation, storage, export, or incorporation into more complex membrane lipid species. In this proposal we aim to investigate if fatty acid chain length may affect the balance of oxidation vs storage in the highly metabolically active tissue, brown adipose tissue. We will primarily investigate the effect of lack of Elovl6, an enzyme responsible for elongating saturated and monounsaturated C12 and longer fatty acids up to C18. Thus the aim of this grant is to investigate the role of fatty acid chain length on control of fatty acid oxidation, focussing specifically on the fatty acid elongase Elovl6. Specifically we propose to investigate: 1) the role of Elovl6 in BAT differentiation, lipogenesis and function in vitro; b) the role of Elovl6 on energy balance and c) the effect of a lack of Elovl6 on maximal thermogenic capacity of BAT. To that end we will use both cellular and genetically modified animal models with a loss/gain of function in Elovl6 to investigate the effect of altered fatty acid chain length on fatty acid oxidation. In vivo models will be characterised using state of the art phenotyping including performing experiments at different temperatures in purposedly built facilities for thermogenic studies. Also we will use a molecular systems biology phenotyping approach using sophisticated lipidomic and transcriptomic profiling integrated into lipid metabolic networks using bioinformatic analysis.

Summary

Food contains different types of fat. There are some suggestions that not all the fats are equal and that there is good and bad fat with respect to their effects in the body. Not too much is known about what fat normally does in the cells of the body. We know that fat can be stored, burned, been sent from one organ to another within the body and more importantly fat are important 'bricks' to build up the different components of the cells. Interestingly not all the fats have the same size, the length of some fats is longer than others and we think that the length of the fat species may be an important determinant whether fat is stored or burn. The best organ to study this is a special type of organ known as brown fat present in children and small animals. This organ can do both, making fat and burning fat so it is the ideal organ to investigate the effect of fat length on these two processes. To study fat length we will investigate the effect of lack and/or excess of Elovl6, a molecule that elongates fat from 12 carbons to 18 carbons. Specifically we propose to investigate: 1) if making fat longer can alter the development of the brown fat organ; b) whether eliminating/increasing the capacity of elongating fat makes the animals fatter/leaner and c) less/more capable of making heat. To that end we will use cells and mice in which we will decrease or increase the capacity to make fat longer and then study the type of fat these animals make using very novel techniques that allow us to know all the types of fats that these animals will have. This information will inform us about which fats are good and which ones are bad and will allow us, for example, to modify the diets of humans and animals to ensure that they have the right type of fats to remain healthy.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	X – not assigned to a current Research Topic
Research Priority	Systems Approach to Biological research
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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