Modulations of muscle protein metabolism by branched-chain amino acids in normal and muscle-atrophying rats.
It has been shown that BCAAs, especially leucine, regulate skeletal muscle protein metabolism. However, it remains unclear how BCAAs regulate muscle protein metabolism and lead to anabolism in vivo. We examined muscle protein synthesis rate and breakdown rate simultaneously during BCAA infusion in muscle atrophy models as well as in normal healthy rats. Corticosterone-treated rats and hindlimb-immobilized rats were used as muscle atrophy models. Muscle protein synthesis rate and breakdown rate were measured as phenylalanine kinetics across the hindlimb. In anesthetized normal rats, BCAAs stimulated muscle protein synthesis despite low insulin concentration and did not suppress muscle protein breakdown. In corticosterone-treated rats, BCAAs failed to restore inhibited muscle protein synthesis, but reduced muscle protein breakdown. Immobilization of hindlimb increased muscle protein breakdown within a day. BCAAs did not change muscle protein metabolism, although essential amino acids (EAAs) suppressed muscle protein breakdown in hindlimb-immobilized rats. We also evaluated changes of fractional synthesis rate (FSR) of skeletal muscle protein during infusion of leucine alone or EAAs for 4 h in anesthetized normal rats. FSR showed a transient increase at 15-30 min of leucine infusion and then declined, whereas FSR stayed elevated throughout EAA infusion. We concluded that 1) BCAAs primarily stimulate muscle protein synthesis in normal rats independently of insulin; 2) EAAs are required to maintain the BCAA stimulation of muscle protein synthesis; and 3) The effects of BCAAs on muscle protein metabolism differ between atrophy models.
Kobayashi
Hisamine
H
Applied Research Department, AminoScience Laboratories, Ajinomoto Co., Kawasaki, Japan. hisamine_kobayashi@ajinomoto.com
Kato
Hiroyuki
H
Hirabayashi
Yuri
Y
Murakami
Hitoshi
H
Suzuki
Hiromi
H
D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D000597:Amino Acids, Branched-Chain; D009124:Muscle Proteins