Leucine supplementation modulates fuel substrates utilization and glucose metabolism in previously obese mice

Authors

  • Elke Binder,

    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
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  • Francisco Javier Bermúdez-Silva,

    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
    3. Laboratorio de Investigación, IBIMA-Hospital Carlos Haya, Malaga, Spain
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  • Melissa Elie,

    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
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  • Thierry Leste-Lasserre,

    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
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  • Ilaria Belluomo,

    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
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  • Samantha Clark,

    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
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  • Adeline Duchampt,

    1. INSERM, Lyon, France
    2. Université de Lyon, Lyon, France
    3. Université Lyon 1, Villeurbanne, France
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  • Gilles Mithieux,

    1. INSERM, Lyon, France
    2. Université de Lyon, Lyon, France
    3. Université Lyon 1, Villeurbanne, France
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  • Daniela Cota

    Corresponding author
    1. NeuroCentre Magendie, Bordeaux, France
    2. NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Université de Bordeaux, Bordeaux, France
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  • Funding agencies: This research was supported by the INSERM, Aquitaine Region and Ajinomoto 3ARP Research Program, European Community's Seventh Framework Programme (FP7-People2009-IEF-251494), and Fondation Recherche Médicale. F.J.B.S. is recipient of a research contract from the National System of Health (Instituto de Salud Carlos III; CP07/00283) and of a BAE from Instituto de Salud Carlos III (BA09/90066). This work was supported by INSERM, Aquitaine Region and Ajinomoto 3ARP research program (to DC), European Community's Seventh Framework Programme FP7-People2009-IEF-251494 (DC and EB) and Fondation Recherche Médicale. F.J.B.S. is recipient of a research contract from the National System of Health (Instituto de Salud Carlos III; CP07/00283) and of a BAE from Instituto de Salud Carlos III (BA09/90066).

  • Disclosure: The authors declared no conflict of interest.

  • Author contributions: E.B. and F.J.B.S. carried out experiments and analyzed data; M.E., T.L.L., I.B., S.C., and A.D. carried out experiments; G.M. analyzed data; E.B. and D.C. wrote the manuscript; all the authors edited and approved the manuscript; D.C. conceived and supervised the study.

Abstract

Objective

High-protein diets favor weight loss and its maintenance. Whether these effects might be recapitulated by certain amino acids is unknown. Therefore, the impact of leucine supplementation on energy balance and associated metabolic changes in diet-induced obese (DIO) mice during and after weight loss was investigated.

Methods

DIO C57BL/6J mice were fed a normocaloric diet to induce weight loss while receiving or not the amino acid leucine in drinking water. Body weight, food intake, body composition, energy expenditure, glucose tolerance, insulin, and leptin sensitivity were evaluated. Q-PCR analysis was performed on muscle, brown and white adipose tissues.

Results

DIO mice decreased body weight and fat mass in response to chow, but supplementation with leucine did not affect these parameters. During weight maintenance, mice supplemented with leucine had improved glucose tolerance, increased leptin sensitivity, and lower respiratory quotient. The latter was associated with changes in the expression of several genes modulating fatty acid metabolism and mitochondrial activity in the epididymal white and the brown adipose tissues, but not muscle.

Conclusions

Leucine supplementation might represent an adjuvant beneficial nutritional therapy during weight loss and maintenance, because it improves lipid and glucose metabolism and restores leptin sensitivity in previously obese animals.

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