The role of long chain fatty acids in the control of energy homeostasis and body composition

Dietary fatty acids are thought to play a causal role in weight gain and obesity. However, data suggests that fatty acids are not all similarly obesogenic. Long chain n-3 polyunsaturated fats have been suggested to favour negative energy balance and a reduction in visceral adiposity. Their use as a functional dietary component to prevent or treat obesity is unclear in rodents and relatively unexplored in humans. I therefore aimed to investigate the effects of long chain n-3 fatty acid dietary enrichment in rats and humans on energy homeostasis and adiposity. I first investigated the effects of long chain n-3 fatty acids on energy homeostasis in rats by comparing a diet rich in fish oils, a naturally rich source of long chain n-3 fatty acids, to an isoenergetic diet based on anhydrous milk fat, a fat rich in saturated and monounsaturated fats and used in the manufacture of processed foods. Male Wistar rats were fed an ad libitum diet based on either 20% or 40% energy from fish oils or anhydrous milk fat for 12 weeks. At high fat levels (40%), fish oil feeding was associated with reduced energy intake compared to the isoenergetic anhydrous milk fat diet. However, there was no significant difference in body weight or adiposity between groups. This suggests that these two different dietary fat types may induce changes in metabolic efficiency or energy expenditure. At moderate fat levels the fish oil fed rats consumed more energy and gained more weight than anhydrous milk fat fed rats, but did not have significantly greater adiposity. I found no change in several markers of energy expenditure (uncoupling protein-1 mRNA expression, circulating thyroid hormone concentration or active behaviour), but further work is required to elucidate the mechanisms through which different dietary fats elicit the observed differences in energy intake and body weight. The high levels of long chain n-3 fatty acid supplementation delivered in rodent feeding studies are not practicable in humans. Therefore, I subsequently investigated the effects of more modest long chain n-3 fatty acid supplementation (2.25g per day of n-3 fatty acids) on energy homeostasis and adiposity in overweight and obese humans in a randomised, double-blind, placebo-controlled pilot study. The effect of long chain n-3 fatty acid supplements on adiposity, metabolic parameters and appetite were measured following 12 weeks of supplementation and following 12 weeks of supplementation in combination with a hypocaloric diet. After 12 weeks of supplementation alone, the long chain n-3 fatty acid supplemented group had non-significant reductions in intrahepatocellular lipid and plasma concentrations of the adipokine leptin. However, there was no significant change in total or visceral adipose tissue. When the supplements were taken in combination with a hypocaloric diet, there was no significant change in either total or visceral adiposity in the long chain n-3 supplemented group. Ad libitum energy intake at a test meal, energy intake calculated from a 72 hour food diary and visual analogue scales also suggested there was no effect of long chain n-3 fatty acid supplementation, on appetite or energy intake, whether alone or in combination with a hypocaloric diet. However, long chain n-3 fatty acid supplementation was associated with an increase in reported food appeal scores. In line with a possible effect of long chain n-3 fatty acid supplementation on the non-homeostatic control of food intake, I specifically examined the effects of long chain n-3 fatty acid supplementation on brain reward centre activation using blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) in response to food picture presentation. The effect of 24 weeks of n-3 fatty acid supplementation and a 12 week energy restriction on brain reward centre revealed no significant differences in BOLD activation in any single region of interest. However, when regions of activation were grouped into a reward pathway neuronal network, activation tended to increase in those participants subjected to a hypocaloric diet and placebo supplementation, whereas those given the long chain n-3 fatty acid supplements tended to have a decrease in BOLD activation. These data suggest that long chain n-3 fatty acids may modulate non-homeostatic reward centre signalling. The studies described in this thesis suggest that long chain n-3 fatty acids may have specific beneficial effects on for example, intrahepatocellular lipid and brain reward centre activation. However, further work is required to conclusively determine whether long chain n-3 fatty acids are useful in the prevention and treatment of obesity and obesity-associated disease.