The role of stress response and circadian genes in the link between excess lipid and muscle insulin resistance [ 2004 - 2006 ]

Research Grant

Researchers: Prof Gregory Cooney (Principal investigator)

Brief description Obesity and its associated conditions of heart disease, reduced insulin action, fatty liver and type 2 diabetes are increasing at an alarming rate worldwide. The epidemic of these conditions appears to be due to an interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of high energy food. The relationship between genes and environment is very complex but it seems clear that increased intake of high fat foods can cause body tissues to accumulate excess fat. This interferes with the way that the hormone insulin controls body glucose utilisation although how this happens has not been fully defined. This grant application will test two possible mechanisms that could help explain the link between increased dietary fat intake and decreased insulin action in muscle. Using microarrays to examine the activity of genes in normal and insulin resistant muscle, we have identified two groups of genes that may be involved in how fat causes insulin resistance. One group of genes is normally associated with stress and we will determine if fats control these genes directly or if fats increase other stress factors which increase the activity of these genes. We will then use novel gene therapy techniques to see if these genes cause insulin resistance in muscle of experimental animals. The second group of genes is related to the mechanisms which regulate daily cycles in the body such as sleep-wake cycles, blood pressure, and eating behaviour. We will examine the activity of these genes over a 24 hour period in muscle from normal animals and insulin resistant animals to determine if disruption of these gene cycles contributes to insulin resistance. We will then perform experiments to establish what processes these genes control. The successful outcome of this grant will determine if these groups of genes can be targeted to help treat lipid-induced insulin resistance in muscle.

Funding Amount $AUD 579,000.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant