Dietary deprivation of each essential amino acid induces differential systemic adaptive responses in mice

Scope: Dietary deprivation of essential amino acids (EAAs) in mammals is known to cause reductions in food intake and body weight. The aim of this study was to determine whether and how mice respond to deprivation of individual EAA species. Methods and results: Dietary deprivation of any single EAA (not non-EAA) in mice led to progressive weight loss in the order of Ile^- > Val^- > Thr^- > Leu^- > Trp^- > His^- > Phe^- > Met^- > Lys^-, which correlated with the reduction in food intake. Decreased levels of the deprived EAAs as well as increased levels of all or some of the other amino acids were detected in the serum, although these levels differed among the diets examined. Serum biochemistry identified significant increases in creatine phosphokinase, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase, and decreases in glucose and triglycerides; computed tomography revealed a marked reduction in abdominal/femoral fat and muscle depots; histology identified diffuse myofiber atrophy in the rectus femoris muscle, all in that approximate order. In contrast, amino acid response, autophagy, and ubiquitination marker genes as well as amino acid transporter genes were induced in both deprived EAA-specific and tissue-specific manners. Conclusion: Dietary deprivation of individual EAAs induced systemic adaptive responses that differed in magnitude and molecular machinery.