RT Journal Article T1 Leucine supplementation protects from insulin resistance by regulating adiposity levels. A1 Binder, Elke A1 Bermúdez-Silva, Francisco J A1 André, Caroline A1 Elie, Melissa A1 Romero-Zerbo, Silvana Y A1 Leste-Lasserre, Thierry A1 Belluomo, Llaria A1 Duchampt, Adeline A1 Clark, Samantha A1 Aubert, Agnes A1 Mezzullo, Marco A1 Fanelli, Flaminia A1 Pagotto, Uberto A1 Layé, Sophie A1 Mithieux, Gilles A1 Cota, Daniela K1 Pérdida de peso K1 Leptina K1 Aminoácidos K1 Ratones K1 Obesidad K1 Alimentación rica en grasa K1 Colesterol K1 Homeostasis AB BACKGROUNDLeucine 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 FINDINGSMale 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 observed.CONCLUSIONS/SIGNIFICANCEThese 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 supplementation. PB Public Library of Science YR 2013 FD 2013-09-25 LK http://hdl.handle.net/10668/1545 UL http://hdl.handle.net/10668/1545 LA en NO Binder E, Bermúdez-Silva FJ, André C, Elie M, Romero-Zerbo SY, Leste-Lasserre T, et al. Leucine supplementation protects from insulin resistance by regulating adiposity levels. PLoS ONE. 2013; 8(9):e74705 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 10, 2025