Leucine increases muscle mitochondrial respiration and attenuates glucose intolerance in diet-induced obesity in Swiss mice

[Display omitted] •Leucine acutely increases mitochondrial respiration through mTORC1 activation.•High-fat diet metabolic impairments are attenuated by chronic leucine treatment.•Leucine chronic supplementation prevents reduction on mitochondrial respiration.•Dietary leucine attenuates mitochondrial morphology alterations caused by obesity. Leucine is an essential amino acid that has been investigated by its participation in the regulation of whole-body metabolism and mitochondrial function. Here, we evaluated acute leucine effects on mitochondrial respiration of skeletal muscle from male Swiss mice in vitro. Additionally, we further investigated the effects of 4-wk leucine ingestion (2.5% on drinking water) on skeletal muscle mitochondrial respiration and morphology of diet-induced obesity (DIO) mice. In vitro, acute leucine increased mitochondrial respiration, and these effects were abolished in the presence of rapamycin. In DIO mice, ingestion of leucine for 4-wk improved glucose tolerance and insulin responsivity. Leucine supplementation also prevented the reduction in mitochondrial respiration, size, and complexity in the soleus skeletal muscle. We conclude that the positive effects of leucine on whole-body metabolism in DIO mice are associated with improvements in skeletal muscle mitochondrial function and morphology. Furthermore, leucine acute effects on mitochondrial respiration are mTORC1 dependent.