Premium
Dietary deprivation of each essential amino acid induces differential systemic adaptive responses in mice
Author(s) -
Kamata Shotaro,
Yamamoto Junya,
Karube Katsuhito,
Ohkubo Rika,
Kasahara Tadashi,
Ishii Isao
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.915.13
Subject(s) - amino acid , medicine , endocrinology , amino acid transporter , transporter , calorie , biology , atrophy , biochemistry , chemistry , gene
Research purpose Dietary deprivation of essential amino acids (EAAs: His, Ile, Leu, Lys, Met, Phe, Thr, Trp, and Val) 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 The complete (amino acid) diet was formulated to contain all proteinogenic amino acids that quantitatively matched the amino acids of the standard rodent dry diet CE‐2 (Japan Clea); their basic composition and calorie contents were equivalent and mice grew well on the complete diet. Deprivation of any single EAA (not non‐EAA) from the complete diet led to progressive weight loss in the order of Ile − > Val − > Thr − > Leu − > Trp − > His − > Phe − > Met − > Lys − after two weeks, 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 CPK, BUN, ALT, and AST, 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, marker genes for amino acid response ( Asns ), autophagy ( LC3b ), and ubiquitination ( Atrogin‐1 ) as well as amino acid transporter genes ( Slc38a , Slc7a5 , Slc7a1 ) were induced in both deprived EAA‐specific and tissue (skeletal muscle, liver, heart, kidney, and small intestine)‐specific manners. When mice were deprived of food for 12 hr and then fed the Ile − diet or the Ala − diet, decreased food intakes were evident as early as 30 min with the Ile − diet, and rapid decreases in serum Ile concentrations preceded it (~10 min). Conclusion Dietary deprivation of individual EAAs induced systemic adaptive responses that differed in magnitude and molecular machinery. Support or Funding Information JPSP KAKENHI Grant Numbers 22590292, 23117716, and 25220103