LEUOBESE · METABOLIC EFFECTS OF LEUCINE SUPPLEMENTATION ON THE PREVENTION AND TREATMENT OF DIET-INDUCED OBESITY
FP7 — People (Marie Curie Actions)
- Duration
- 2010-07-01 → 2012-06-30
- EU contribution
- €166,146
- Participants
- 1
- Scheme
- MC-IEF
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Results in brief
metabolic effects of leucine supplementation on the prevention and treatment of diet-induced obesity
Project context and objectives Obesity 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 results The 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.
Data: CORDIS, © European Union
Project objective
Among the branched-chain amino acids, leucine is known to decrease food intake via mTORC1-dependent mechanisms. We now hypothesize that leucine protects against diet-induced obesity (DIO) by having a beneficial effect on inflammation and insulin sensitivity. We postulate that these effects are due to leucine’s ability to affect intracellular pathways that modulate energy balance as well as protein synthesis, inflammation and mitochondrial function. To study leucine’s effects on the development of DIO, in Aim 1 C57BL/6 mice will receive either low-fat chow or high-fat diet (HFD), and half will receive leucine in the drinking water. After 12 weeks, we will evaluate glucose tolerance and insulin sensitivity, in vivo body composition and energy expenditure. Food intake will be assessed in these mice after receiving acute leptin, to verify whether leucine supplementation halts the development of DIO-associated leptin resistance. At sacrifice, tissues and blood will be collected for assessment of inflammatory cytokines. Activation of the mTOR pathway and of the inflammatory pathway involving nuclear factor-kappa B and SOCS-3 will be studied in the hypothalamus. mRNA levels of hypothalamic neuropeptides regulating food intake and of genes involved in thermogenesis and mitochondrial activity will be measured. In Aim 2, we will study leucine’s effects once the DIO phenotype has developed. Half a group of DIO mice will continue on HFD for 12 weeks; the other half will be switched to chow to verify that (a) leucine supplementation facilitates body weight loss, (b) leucine’s effects in DIO mice resemble those obtained by returning mice to chow. Animals will then undergo the metabolic and molecular analysis described earlier. This novel project will explore leucine’s actions during DIO and body weight loss. Our findings will clarify whether and in which way this nutrient might ease the obese condition and help halt its epidemic.
Original text from CORDIS.
Participants
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union