Insulin as a regulator of postprandial lipaemia in obesity

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People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in our laboratory have found that in obesity the production of these fats and the clearance is disturbed probably because of an inability to properly respond to insulin. The hormone insulin critically regulates synthesis, secretion and clearance of lipids, however, in obese subjects the concentration of insulin is abnormally elevated. We have explored the impact of sustained weight reduction on the production and clearance of lipids from blood. Collectively, weight loss leads to an improvement in fat metabolism because of increased sensitivity to the normal effects of insulin. However, weight reduction alone is rarely able to fully correct the disturbances in fat metabolism and it is likely that the individuals are still at risk of developing vascular disease. In this proposal, we wish to explore the efficacy of two agents which could potentially ameliorate lipid disturbances in diabetes by enhancing the regulatory effects of insulin. We believe that long term correction of the lipid abnormalities in obesity will reduce the frequency and progression of cardio- and peripheral-vascular disease.