[Frontiers in Bioscience, Landmark, 20, 796-813, January 1, 2015] 796 1. ABSTRACT The metabolic roles for L-leucine, an essential branched-chain amino acid (BCAA), go far beyond serving exclusively as a building block for de novo protein synthesis. Growing evidence shows that leucine regulates protein and lipid metabolism in animals. Specifically, leucine activates the mammalian target of rapamycin (mTOR) signaling pathway, including the 70 kDa ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1) to stimulate protein synthesis in skeletal muscle and adipose tissue and to promote mitochondrial biogenesis, resulting in enhanced cellular respiration and energy partitioning. Activation of cellular energy metabolism favors fatty acid oxidation to CO 2 and water in adipocytes, lean tissue gain in young animals, and alleviation of muscle protein loss in aging adults, lactating mammals, and food-deprived subjects. As a functional amino acid, leucine holds great promise Nutritional and regulatory roles of leucine in muscle growth and fat reduction Yehui Duan 1,2 , Fengna Li 1 , Hongnan Liu 1 , Yinghui Li 1,2 , Yingying Liu 1,2 , Xiangfeng Kong 1 , Yuzhe Zhang 1 , Dun Deng 1 , Yulong Tang 1 , Zemeng Feng 1 , Guoyao Wu 1 , Yulong Yin 1 1 Chinese Academy of Science, Institute of Subtropical Agriculture, Research Center for Healthy Breeding Livestock and Poultry, Hunan Engineering and Research Center for Animal and Poultry Science, Key Laboratory of Agroecology in Subtropical Region, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central China, Ministry of Agriculture, Changsha 410125, Hunan, Peoples R China; 2 University of Chinese Academy of Sciences, Beijing 100039, China; and 3 Department of Animal Science, Texas A&M University, College Station, TX, USA 77843 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Roles of leucine in protein synthesis 3.1. How leucine enters the cell to regulate mTORC1 signaling 3.2. The mechanisms for leucine to stimulate protein synthesis via mTORC1 signaling 3.3. Role of insulin in leucine-induced protein synthesis in muscle 3.4. Protein synthesis via mTORC1 signaling and endoplasmic reticulum stress 4. The mechanisms of leucine on energy partitioning between skeletal muscle and adipocytes 4.1. Fatty acid oxidation provides energy required for leucine-induced protein synthesis 4.2. Mitochondrial biogenesis is involved in the role of leucine in energy metabolism 4.3. Cytokines secreted by adipose and muscle may regulate energy partitioning 4.4. mTOR and AMPK may regulates leucine-induced energy partitioning 5. Summary and perspectives 6. Acknowledgement 7. References to enhance the growth, efficiency of food utilization, and health of animals and humans. 2. INTRODUCTION Sufficient evidence has pointed out that leucine, a nutritionally essential branched-chain amino acid, plays a unique signaling role in both adipose tissue and skeletal muscle. In these cells, leucine stimulates protein synthesis via the mTOR signaling pathway, mitochondrial biogenesis, and fatty acid oxidation (1, 2). Protein synthesis is the major energy-consuming process in the cell (3). In particular, both mRNA translation and ribosomal biogenesis processes, which are strongly affected by the mTOR pathway, consume high levels of cellular energy (4). Moreover, previous studies indicate that leucine regulates muscle protein synthesis and adipocyte lipid metabolism to provide