Resistance Exercise-induced Regulation of Muscle Protein Synthesis to Intraset Rest

Med Sci Sports Exerc. 2020 May;52(5):1022-1030. doi: 10.1249/MSS.0000000000002213.


During a traditional set configuration of resistance exercise (TRD), characterized by a continuous completion of repetitions, a decrease in power output tends to occur throughout a set of repetitions. Inclusion of intraset rest, otherwise known as a cluster set configuration (CLU), counteracts this power decline. However, the effect of a CLU configuration on postexercise myofibrillar protein synthesis rates (MPS) and anabolic signaling has not been investigated.

Purpose: We aimed to determine if any mechanistic differences exist between TRD and CLU signaling events associated with muscle anabolism.

Methods: In randomized crossover trials, eight resistance-trained participants (23 ± 1 yr, 81 ± 4.7 kg, body fat: 18% ± 1.9%; 1 repetition maximum [1RM], 150 ± 9.1 kg) performed an acute bout of CLU (4 sets × (2 × 5) repetitions, 30-s intraset rest, 90-s interset rest) and TRD (4 sets × 10 repetitions, 120-s interset rest) barbell back squats at approximately 70% 1RM with total volume load equated during primed continuous L-[ring-C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at rest and after exercise at 0, 2, and 5 h.

Results: There was no difference in postexercise MPS between the CLU and TRD condition (P > 0.05) and no changes in phosphorylation of mTORC1 downstream targets (p70S6K and 4EBP1). Total and phosphorylated yes-associated protein on Ser127 transiently increased (P < 0.01) immediately after exercise (t = 0) in CLU (~2.1-fold) and TRD condition (~2.2-fold).

Conclusions: Our results show that CLU is a viable anabolic option by preserving power output with similar MPS stimulation when compared with the TRD condition in trained young adults.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Amino Acids / blood
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Female
  • Humans
  • Insulin / blood
  • Lactic Acid / blood
  • MAP Kinase Signaling System
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / biosynthesis
  • Muscle Proteins / biosynthesis*
  • Myofibrils / metabolism*
  • Perception / physiology
  • Phosphorylation
  • Physical Exertion / physiology
  • Resistance Training / methods*
  • Rest*
  • Transcription Factors / biosynthesis
  • YAP-Signaling Proteins
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • Blood Glucose
  • Insulin
  • Muscle Proteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Lactic Acid
  • Mechanistic Target of Rapamycin Complex 1