Nutritional modulation of hepatic lipid metabolism in health and disease

The objective of this thesis was to assess the impact of altering macronutrient intakes on hepatic lipid metabolism. Two separate studies were performed, with liver triglyceride content being the principal outcome of both. In the first study 32 healthy and centrally overweight males were randomised to 2 periods, each of 2 weeks, of either a high fructose or glucose intake in a non-crossover fashion. Isoenergetic status was maintained by providing foodstuffs during the first period, followed by a 6 week washout and then a second period of ad libitum overfeeding. In the second study 55 patients with biopsy proven non-alcoholic fatty liver disease were randomised to 3 months 5g a day of capsules containing either n-3 polyunsaturated fatty acid or oleic enriched sunflower oil. The main findings are summarised. High intakes of fructose and glucose in the isoenergetic period resulted in a stable weight, and no change in hepatic, serum and ectopic triglyceride content. There was a raised serum uric acid with fructose. During the hyperenergetic period there was a tendency for greater uric acid with fructose, whilst both groups had a matched weight gain, elevation of liver biochemistry and an increase in hepatic, serum and muscle triglycerides. Changes in liver biochemistry and triglycerides were associated with changes in weight. During both periods there was calorimetric evidence for a shift in whole body metabolism towards that reflective of a high carbohydrate intake. There was no alteration in renal function or cardiovascular haemodynamic parameters or consistent change in insulin resistance. The n-3 polyunsaturated versus oleic acid study resulted in significant alterations of serum fatty acid profiles between the groups, which were in line with the capsules’ contents. These changes however failed to translate, in the whole group, to any detected metabolic or hepatic changes beyond a reduction in serum triglyceride with n-3 polyunsaturated fatty acids. Only 43 of the 55 patients had elevated liver triglycerides on baseline MRI. Amongst this 43 there was a reduction in liver triglyceride with n-3 polyunsaturated fatty acids, but no other associated metabolic changes. The uric acid findings support the notion of fructose and glucose differing in their pre triose metabolism. There was however no differing outcomes in terms of lipid synthesis or storage. There was a suggestion of reduced liver triglycerides with n-3 polyunsaturated fatty acids though this was an isolated result only found amongst those with a steatotic liver at baseline. Ultimately the exquisite sensitivity of the liver to nutrient intakes was highlighted by the 0.8% gain in weight in the fructose / glucose study resulting in a 24% increase in liver lipid. This affirms the notion that dietary energy intakes have a profound influence on hepatic metabolism, but there is no evidence from this thesis that this influence is macronutrient specific. In the future macronutrient comparisons need to be made.EThOS - Electronic Theses Online ServiceGBUnited Kingdo