Zeanandin Gilbert, Balage Michèle, Schneider Stéphane M, Dupont Joëlle, Hébuterne Xavier, Mothe-Satney Isabelle, Dardevet Dominique
Centre Hospitalier Universitaire de Nice, Pôle Digestif, Nice, France.
Age (Dordr). 2012 Apr;34(2):371-87. doi: 10.1007/s11357-011-9246-0. Epub 2011 Apr 7.
Leucine acts as a signal nutrient in promoting protein synthesis in skeletal muscle and adipose tissue via mTOR pathway activation, and may be of interest in age-related sarcopenia. However, hyper-activation of mTOR/S6K1 has been suggested to inhibit the first steps of insulin signaling and finally promote insulin resistance. The impact of long-term dietary leucine supplementation on insulin signaling and sensitivity was investigated in old rats (18 months old) fed a 15% protein diet supplemented (LEU group) or not (C group) with 4.5% leucine for 6 months. The resulting effects on muscle and fat were examined. mTOR/S6K1 signaling pathway was not significantly altered in muscle from old rats subjected to long-term dietary leucine excess, whereas it was increased in adipose tissue. Overall glucose tolerance was not changed but insulin-stimulated glucose transport was improved in muscles from leucine-supplemented rats related to improvement in Akt expression and phosphorylation in response to food intake. No change in skeletal muscle mass was observed, whereas perirenal adipose tissue mass accumulated (+45%) in leucine-supplemented rats. A prolonged leucine supplementation in old rats differently modulates mTOR/S6K pathways in muscle and adipose tissue. It does not increase muscle mass but seems to promote hypertrophy and hyperplasia of adipose tissue that did not result in insulin resistance.
亮氨酸作为一种信号营养素，通过激活mTOR途径促进骨骼肌和脂肪组织中的蛋白质合成，可能与年龄相关的肌肉减少症有关。然而，有人提出mTOR/S6K1的过度激活会抑制胰岛素信号传导的第一步，并最终促进胰岛素抵抗。在18个月大的老年大鼠中，研究了长期补充亮氨酸饮食对胰岛素信号传导和敏感性的影响。这些大鼠喂食含15%蛋白质的饮食，其中一组（LEU组）额外补充4.5%的亮氨酸，另一组（C组）不补充，持续6个月。检测了对肌肉和脂肪产生的影响。长期饮食中亮氨酸过量的老年大鼠肌肉中的mTOR/S6K1信号通路没有显著改变，而在脂肪组织中该信号通路增强。总体葡萄糖耐量没有变化，但与进食后Akt表达和磷酸化的改善相关，补充亮氨酸的大鼠肌肉中胰岛素刺激的葡萄糖转运得到改善。未观察到骨骼肌质量的变化，而补充亮氨酸的大鼠肾周脂肪组织质量增加（+45%）。老年大鼠长期补充亮氨酸对肌肉和脂肪组织中的mTOR/S6K途径有不同的调节作用。它不会增加肌肉质量，但似乎会促进脂肪组织的肥大和增生，且不会导致胰岛素抵抗。
