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Title: Studies on the fatty acid composition of human serum, with special reference to the influence of hormones and other agents
Author: Jurand, J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1968
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A modified technique for separation of serum free fatty acids (FFA), t riglycerides, phospholipids and cholesterol esters by adsorption chromatography on a system of two columns, silicic acid and Florisil, has been elaborated for preparing samples for gas-liquid chromatographic analysis of serum lipid fatty acids. An attempt was made to study the changes in fatty acid composition of the various lipids in response to factors influencing fatty acid mobilisation. The following stimuli of fatty acid mobilisation were investigated: thyroid hormone, human growth hormone (HGH),noradrenaline, prolonged fasting, and acute and chronic ischaemic heart disease. The effects of thyroid hormones were studied 1) after administration of LT₃ to normal subjects; 2) after thyroid hormone therapy to hypothyroid subjects and 3) after antithyroid therapy to thyrotoxic subjects. The effects of HGH were studied 1) during the daily administration of HGH; 2) hourly after HGH injection; and 3) in patients with acromegaly. The effects of noradrenaline were studied during its infusion. The effects of fasting were studied when an overnight fast was prolonged by 8 hours. The effects of acute ischaemic heart disease were studied on the day of myocardial infarction and on two subsequent consecutive days. The effects of chronic ischaemic heart disease were studied in patients with angina pectoris, and those with a past history of myocardial infarction. One control group consisted of middle aged males, and a second of postmenopausal females. Percentage composition studies have revealed that increased mobilisation of serum FFA due to any of the adipokinetic factors studied was accompanied by statistically significant increases in the percentage composition of serum FFA oleic acid. These increases in oleic acid percentages were mostly accompanied by parallel decreases in the percentage of FFA saturated acids: stearic and palmitic acids. It is proposed that increases in the percentage of FFA oleic acid were due to its higher activity in transportation compared with saturated acids, in the aqueous medium of adipose cells and plasma. This is thought to be due to the physical properties of oleic acid, its greater hydrophilic property and also, possibly, its greater affinity for albumin. The changes in triglyceride fatty acids were not uniform for all the influences studied. Triglyceride oleate was significantly lowered by antithyroid therapy in hyperthyroid subjects, but no significant increases could be proved as a result of thyroid therapy in hypothyroid subjects, thus suggesting that the increased incorporation of oleic acid into triglyceride fatty acids may be inhibited in some subjects. Administration of HGH did not affect triglyceride oleate; observations made during daily administration of HGH, and in the disease of acromegaly, suggest that HGH may promote a higher degree of saturation in triglyceride fatty acids. In subjects with acute myocardial infarction, the triglyceride fatty acid pattern resembled that of hyperthyroid subjects. In chronic ischaemic heart disease, the pattern of triglyceride fatty acids did not differ from normal. The lack of parallel increases in percentages of triglyceride oleate with increases in percentages of FFA oleic acid in patients with chronic ischaemic heart disease suggests that incorporation of oleic acid into triglyceride fatty acids in these patients is possibly lower. In the phospholipid fatty acids, similarly, no common pattern of changes was noted for the different stimuli studied. The percentage of phospholipid palmitate decreased significantly immediately after noradrenaline infusion. Opposite changes were noted after prolonged fasting. Equally high levels were observed shortly after myocardial infarction as in ischaemic patients with hyperphospholipidaemia. The percentage of phospholipid arachidonate increased significantly following thyroid hormone therapy in hypothyroid subjects. Phospholipid arachidonate also showed an immediate rise during noradrenaline infusion. The latter observation supports the concept that thyroid hormone activity may be mediated through the action of endogenous catecholamines. The percentage composition studies on cholesteryl fatty acids suggest that changes in serum FFA concentrations (due to HGH daily dose, thyroid hormone and antithyroid therapy, acute myocardial infarction) produce in most cases directly related changes in cholesteryl oleate percentages and inversely - related changes in cholesteryl linoleate. It is probable that the increased mobilisation of serum FFA, accompanied by predominant increases in FFA oleic acid, may promote the formation of cholesteryl oleate. Cholesteryl arachidonate was shown to be materially influenced and controlled by thyroid function: a significant increase in the percentage of cholesteryl arachidonate occurred after thyroid hormone therapy in hypothyroid subjects, and a significant decrease occurred after antithyroid therapy in thyrotoxic subjects; the thyrotoxic patients had percentage levels of cholesteryl arachidonate twice as high as those of the hypothyroid patients. The results agree with the suggestion of Ellefson and Mason (1964) that thyroid hormones stimulate an increased synthesis of arachidonic acid from linoleic acid. An attempt was made to discuss the results in relation to certain metabolic studies, and to postulate possible implications of the predominant increase in serum FFA oleic acid percentage at the time when fatty acids are mobilised from the storage sites.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available