Abstract
The studies described in this thesis were designed to evaluate the role of gastrointestinal hormones in the regulation of deposition and mobilisation of lipids in adipose tissue. The role of gastrointestinal and pancreatic hormones in fatty acid synthesis and lipolysis was evaluated in vitro using explants of rat epididymal adipose tissue. With the exceptions of insulin, glucagon and secretin, in vitro effects of the hormones investigated on direct control of fatty acid synthesis and on lipolysis were small. Secretin had a pronounced lipolytic effect in rat adipose tissue, especially when administered in combination with insulin. This hormone may regulate hormone-sensitive lipase and be important in mobilisation of lipid stores. GLP-2 was shown to have a lipogenic effect when administered in conjunction with insulin. This is of particular interest since no physiological role for GLP-2 has been established to date. Two in vivo dietary studies were undertaken in rats. In the first study dietary inclusion of fish oil (5%) resulted in elevated rates of basal and insulin-stimulated fatty acid synthesis in rat epididymal adipose tissue in vitro. The enhancement of insulin sensitivity of this tissue may have arisen from modification of adipocyte plasma membrane fluidity due to incorporation of w-3 polyunsaturated fatty acids from fish oil. In the second study dietary inclusion of soluble non-starch polysaccharide was without effect on basal and insulin-stimulated fatty acid synthesis in vitro. An in vivo study using human volunteers investigated postprandial hormone secretion and lipoprotein lipase activity in lean and obese subjects in response to carbohydrate and fat meals. No differences in post-heparin plasma lipoprotein lipase activity were observed. There was no difference in circulating concentrations of GIP in response to the test meals by obese and lean subjects. However, postprandial secretion of GLP-1 (7-36) amide in response to the carbohydrate meal but not the fat meal was attenuated in obese subjects. These hormones cannot be responsible for causing the hyperinsulinaemia of obesity, but reduced concentrations of GLP-1 (7-36) amide may contribute to insulin resistance in obesity. The attenuated postprandial secretion profile of GLP-1 (7-36) amide also suggests a role for GLP-1 (7-36) amide in satiety in humans.