Role of apoCIII in the regulation of lipoprotein metabolism in obesity [ 2002 - 2004 ]

Research Grant

Researchers: Prof Hugh Barrett (Principal investigator) ,  Prof Gerald Watts ,  Prof Trevor Redgrave

Brief description Obesity is an increasing problem in Australia. Associated with the state of obesity are elevated levels of blood fats and thus an increased risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In obesity, the secretion of blood fats, or lipoproteins, is elevated compared with non-obese individuals. In addition, the mechanisms responsible for the clearance of these fats from the blood are impaired resulting in elevated levels of fat circulating in the body. A particular protein, called apolipoprotein CIII, plays an important role in the regulation of lipoprotein metabolism. Obese subjects have elevated levels of this apoprotein and we have hypothesised that this is responsible for the impaired lipoprotein clearance observed in these subjects. In general, obese subjects are insulin resistant, although they may not be frank diabetics. Blood insulin levels regulate apolipoprotein CIII concentrations, however, in a state of insulin resistance, as seen in obese subjects, apolipoprotein CIII levels are elevated resulting in high blood fat levels. The focus of this research project is to determine if the level and production of apolipoprotein CIII is elevated in obese subjects compared with non-obese individuals by performing metabolic studies. In addition, we will investigate the effect of statins and fish oil, regulators of cholesterol and triglyceride synthesis respectively, on apolipoprotein CIII levels to assess the association between this and the clearance time of blood fats. If our hypothesis is correct, these studies will demonstrate a new mechanism of action of the statins and fish oil that will aid in the treatment of elevated blood fats and thus reduce the risk for heart disease in this important target population.

Funding Amount $AUD 240,320.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant