Final Report Summary - LEUOBESE (metabolic effects of leucine supplementation on the prevention and treatment of diet-induced obesity) Project context and objectivesObesity is a major health problem in developed countries and a growing one in the developing world. Obesity-related diseases currently account for up to 8 % of health costs in Europe. Diet composition is particularly important in determining metabolic changes that might lead to obesity, insulin resistance and the development of diabetes and cancer. In particular, recent studies have demonstrated how nutrients (glucose, fatty acids and amino acids) do not only represent a source of energy for the organism, but work as intracellular signals able to modulate intracellular pathways affecting both behaviour and metabolism.Recent evidence has also shown that among the amino acids, leucine is able to strongly reduce food intake. However, the available information obtained from animal studies about leucine's actions on energy balance and metabolism during diet-induced obesity (DIO) is presently equivocal. In particular, while it has been shown that leucine supplementation reduces diet-induced body weight gain and adiposity and improves insulin sensitivity and dyslipidemia in DIO mice, other investigations were unable to replicate these findings, although reporting that leucine supplementation in DIO rodents could improve glycemia.Therefore, in the current project we have proposed to investigate the metabolic effects of leucine supplementation on the development of DIO in mice; to determine its effects once the DIO phenotype has developed; and to clarify the potential beneficial action of leucine supplementation during body-weight loss.Project resultsThe main results achieved while carrying out the project clearly demonstrate that leucine supplementation prevents body-weight gain and improves insulin sensitivity by mainly affecting the amount of adipose tissue present in the body. Our investigation has also shown that while supplementation of leucine in mice that have already developed DIO might be ineffective, its supplementation during body-weight loss improves metabolic performance and fuel substrate utilisation. Taking into account the epidemic of obesity and the medical, economic and social burden that this metabolic disorder represents, the obtained findings are extremely timely and relevant. In fact, they not only provide further information on the mechanisms engaged by leucine in regulating energy balance in obesity and body-weight loss but represent new evidence that might lead in the future to new dietary or nutritional interventions able to help ease the obese condition in humans and halt its epidemic. In addition, the relevance of the topic investigated in the current project is further highlighted by the recent interest of the European Union in funding large projects investigating the impact of specific nutrient-oriented strategies on general health and metabolic disorders in particular. Overall, we therefore believe that in the long run our findings might be of interest for both health policy-makers and the civil society.
