Leucine, but not isoleucine or valine, affects serum lipid profiles and browning of WAT in mice

Branched chain amino acids (BCAA), especially leucine (Leu), have been reported to decrease fat deposition. However, opposite effects of BCAA on lipid metabolism have been observed. To determine the role of BCAA in lipid metabolism, an amino acid-defined diet was formulated and C57BL/6J mice were assigned into the following groups: amino acid-defined control diet and control diet supplemented with Leu, isoleucine, or valine. Nitrogen was balanced by proportionally mixed amino acids except BCAA. Results showed that dietary Leu supplementation significantly increased the levels of serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and urea nitrogen. Metabolomics showed that biosynthesis of unsaturated fatty acids was altered by Leu supplementation. Leu treatment up-regulated the expression of genes related to fat synthesis and down-regulated the expression of genes related to fatty acid synthesis. Furthermore, the genes and proteins of selective markers involved in browning of white adipose tissue (WAT) were up-regulated by dietary supplementation with Leu. This study indicated that dietary supplementation with Leu, but not isoleucine or valine, significantly affected lipid metabolism by regulating lipid metabolism-related genes and serum fatty acid concentration, providing a new tool in the management of obesity and metabolic disorders.