Distribution of dietary protein intake in daily meals influences skeletal muscle hypertrophy via the muscle clock

Shinya Aoyama; Hyeon-Ki Kim; Rina Hirooka; Mizuho Tanaka; Takeru Shimoda; Hanako Chijiki; Shuichi Kojima; Keisuke Sasaki; Kengo Takahashi; Saneyuki Makino; Miku Takizawa; Masaki Takahashi; Yu Tahara; Shigeki Shimba; Kazuyuki Shinohara; Shigenobu Shibata

doi:10.1016/j.celrep.2021.109336

Distribution of dietary protein intake in daily meals influences skeletal muscle hypertrophy via the muscle clock

Cell Rep. 2021 Jul 6;36(1):109336. doi: 10.1016/j.celrep.2021.109336.

Authors

Affiliations

¹ Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan; Organization for University Research Initiatives, Waseda University, Tokyo 162-8480, Japan; Department of Neurobiology & Behavior, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
² Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan; Organization for University Research Initiatives, Waseda University, Tokyo 162-8480, Japan.
³ Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.
⁴ Institute for Liberal Arts, Tokyo Institute of Technology, Tokyo 152-8550, Japan.
⁵ Department of Health Science, School of Pharmacy, Nihon University, Chiba 274-8555, Japan.
⁶ Department of Neurobiology & Behavior, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
⁷ Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan. Electronic address: shibatas@waseda.jp.

PMID: 34233179
DOI: 10.1016/j.celrep.2021.109336

Abstract

The meal distribution of proteins throughout the day is usually skewed. However, its physiological implications and the effects of better protein distribution on muscle volume are largely unknown. Here, using the two-meals-per-day feeding model, we find that protein intake at the early active phase promotes overloading-induced muscle hypertrophy, in a manner dependent on the local muscle clock. Mice fed branched-chain amino acid (BCAA)-supplemented diets at the early active phase demonstrate skeletal muscle hypertrophy. However, distribution-dependent effects are not observed in Clock^Δ19 or muscle-specific Bmal1 knockout mice. Additionally, we examined the relationship between the distribution of proteins in meals and muscle functions, such as skeletal muscle index and grip strength in humans. Higher muscle functions were observed in subjects who ingested dietary proteins mainly at breakfast than at dinner. These data suggest that protein intake at breakfast may be better for the maintenance of skeletal muscle mass.

Keywords: BCAA; Bmal1; autophagy; breakfast; circadian rhythm; clock; dietary protein; hypertrophy; protein distribution; skeletal muscle.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

ARNTL Transcription Factors / deficiency
ARNTL Transcription Factors / metabolism
Aged
Amino Acids, Branched-Chain / administration & dosage
Amino Acids, Branched-Chain / blood
Animals
Autophagy / drug effects
Circadian Clocks / drug effects
Circadian Clocks / physiology*
Circadian Rhythm / drug effects
Circadian Rhythm / physiology
Dietary Proteins / pharmacology*
Disease Models, Animal
Feeding Behavior*
Female
Gene Expression Regulation / drug effects
Humans
Hypertrophy
Male
Meals*
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal / drug effects
Muscle, Skeletal / pathology*
Muscle, Skeletal / physiopathology*
Time Factors

Substances

ARNTL Transcription Factors
Amino Acids, Branched-Chain
Bmal1 protein, mouse
Dietary Proteins