Leucine supplementation protects from insulin resistance by regulating adiposity levels.

Elke Binder, Francisco J. Bermúdez-Silva, Caroline André, Melissa Elie, Silvana Y. Romero-Zerbo, Thierry Leste-Lasserre, llaria Belluomo, Adeline Duchampt, Samantha Clark, Agnes Aubert, Marco Mezzullo, Flaminia Fanelli, Uberto Pagotto, Sophie Layé, Gilles Mithieux, Daniela Cota
PLoS ONE. 2013-09-25; 8(9): e74705
DOI: 10.1371/journal.pone.0074705

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1. PLoS One. 2013 Sep 25;8(9):e74705. doi: 10.1371/journal.pone.0074705. eCollection

Leucine supplementation protects from insulin resistance by regulating adiposity

Binder E(1), Bermúdez-Silva FJ, André C, Elie M, Romero-Zerbo SY, Leste-Lasserre
T, Belluomo I, Duchampt A, Clark S, Aubert A, Mezzullo M, Fanelli F, Pagotto U,
Layé S, Mithieux G, Cota D.

Author information:
(1)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U862, Bordeaux, France ; Université de Bordeaux, Neurocentre Magendie,
Physiopathologie de la Plasticité Neuronale, U862, Bordeaux, France.

BACKGROUND: Leucine supplementation might have therapeutic potential in
preventing diet-induced obesity and improving insulin sensitivity. However, the
underlying mechanisms are at present unclear. Additionally, it is unclear whether
leucine supplementation might be equally efficacious once obesity has developed.
METHODOLOGY/PRINCIPAL FINDINGS: Male C57BL/6J mice were fed chow or a high-fat
diet (HFD), supplemented or not with leucine for 17 weeks. Another group of
HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an
adiposity level comparable to that of HFD-Leu mice. Finally, a third group of
mice was exposed to HFD for 12 weeks before being chronically supplemented with
leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat
mass by increasing energy expenditure, fatty acid oxidation and locomotor
activity in vivo. The decreased adiposity in HFD-Leu mice was associated with
increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue,
better insulin sensitivity, increased intestinal gluconeogenesis and preservation
of islets of Langerhans histomorphology and function. HFD-pairfat mice had a
comparable improvement in insulin sensitivity, without changes in islets
physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and
HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve
insulin sensitivity. In contrast, when leucine was supplemented to already obese
animals, no changes in body weight, body composition or glucose metabolism were
CONCLUSIONS/SIGNIFICANCE: These findings suggest that leucine improves insulin
sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than
directly acting on peripheral target organs. However, beneficial effects of
leucine on intestinal gluconeogenesis and islets of Langerhans’s physiology might
help prevent type 2 diabetes development. Differently, metabolic benefit of
leucine supplementation is lacking in already obese animals, a phenomenon
possibly related to the extent of the obesity before starting the

DOI: 10.1371/journal.pone.0074705
PMCID: PMC3783457
PMID: 24086364 [Indexed for MEDLINE]

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