Leucine supplementation protects from insulin resistance by regulating adiposity levels.
Leucine supplementation protects from insulin resistance by regulating adiposity levels.
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DOI：
10.1371/journal.pone.0074705
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cota D
中科院分区：
文献类型：
--
作者：
Binder E;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
补充亮氨酸可能在预防饮食诱导的肥胖和改善胰岛素敏感性方面具有治疗潜力。然而，其潜在机制目前尚不清楚。此外，还不清楚一旦肥胖发生，亮氨酸补充剂是否同样有效。雄性C57 BL/6 J小鼠喂食补充或不补充亮氨酸的食物或高脂肪饮食（HFD）17周。另一组HFD喂养的小鼠（HFD-配对脂肪组）限制食物，以达到与HFD-Leu小鼠相当的肥胖水平。最后，第三组小鼠在长期补充亮氨酸之前暴露于HFD 12周。在HFD喂养的小鼠中补充亮氨酸通过增加体内能量消耗、脂肪酸氧化和运动活性来降低体重和脂肪量。HFD-Leu小鼠的肥胖减少与棕色脂肪组织中解偶联蛋白3（UCP-3）表达增加、胰岛素敏感性提高、肠道新生增加以及胰岛组织形态学和功能的保护有关。HFD对胖小鼠在胰岛素敏感性方面有相当的改善，而胰岛生理学或肠道新生没有变化。值得注意的是，HFD-Leu和HFD-pairfat小鼠的肝脏脂质含量都有所降低，这可能有助于改善胰岛素敏感性。相比之下，当亮氨酸补充到已经肥胖的动物中时，没有观察到体重、身体组成或葡萄糖代谢的变化。这些发现表明，亮氨酸主要通过减少肥胖来改善HFD喂养小鼠的胰岛素敏感性，而不是直接作用于外周靶器官。然而，亮氨酸对肠道新生和胰岛生理学的有益作用可能有助于预防2型糖尿病的发展。因此，亮氨酸补充的代谢益处在已经肥胖的动物中缺乏，这一现象可能与开始补充之前的肥胖程度有关。
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. 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 observed. 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 supplementation.
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影响因子：
7.7
作者：
HAYEK, A;WOODSIDE, W
通讯作者：
WOODSIDE, W
DOI：
10.1097/mco.0b013e32832c4d6a
发表时间：
2009-07-01
影响因子：
3.1
作者：
Mithieux, Gilles;Andreelli, Fabrizio;Magnan, Christophe
通讯作者：
Magnan, Christophe
影响因子：
6.5
作者：
Pitman, Jeffrey L.;Bonnet, David J.;Gekakis, Nicholas
通讯作者：
Gekakis, Nicholas
影响因子：
3.7
作者：
Macotela Y;Emanuelli B;Bång AM;Espinoza DO;Boucher J;Beebe K;Gall W;Kahn CR
通讯作者：
Kahn CR
影响因子：
29
作者：
Blouet C;Schwartz GJ
通讯作者：
Schwartz GJ