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

Aoyama et al. 2021

What the Study Says

They report that the skeletal muscle hypertrophy is dependent on the dietary protein distribution in mice having two-meals- per-day feeding. They show here that BCAAs are involved in inducing distribution-dependent hypertrophic effects. Additionally, the hypertrophic effects of protein distribution were not observed in clock disrupted mice, such as Clock mutant (ClockD19) mice and muscle-specific Bmal1 knockout (MKO) mice. Finally, they showed that the distribution of protein intake at breakfast was positively correlated with the skeletal muscle volume in healthy older women.

 

Animal Research

In the animal experiments, they found that the response of skeletal muscle hypertrophy to overloading differed with the daily protein intake pattern. A similar distribution-dependent response was observed in the mice fed BCAA-supplemented diets, but not in those that were fed diets supplemented with amino acids other than BCAAs. In addition, the expression levels of Igf1, Myog, and Myf5 and the autophagy marker (LC3B-II levels) were higher in the overloaded muscles of mice fed a high-protein diet in the early active phase.

The SMI and grip strength were higher in subjects who habitually consumed a high protein breakfast than in those who had a high protein dinner. The ratio of overloaded muscle weight to sham muscle weight in the high protein breakfast fed mice in the 8.5% group was 17% higher than that in the high protein dinner fed mice in the 11.5% group, even though the daily total protein intake in the former was lower than that in the latter

In the study, feeding a high-protein meal in the late active phase (defined as dinner) attenuated muscle hypertrophy in mice. In comparison, mice that were fed a high-protein meal at the early active phase (defined as breakfast) showed the highest response of muscle hypertrophy to overloading.

Possible Mechanisms

There are two possible explanations for this finding. First, the distribution of protein intake could influence the anabolic processes of overloading-induced muscle hypertrophy because this process was drastically altered immediately after synergistic ablation (Schiaffino et al., 2013). Second, the study period was too short, because Norton et al. (2017) reported an equal distribution of protein intake in daily meals for a long time, 11 weeks, maintained and/or increased volume of intact muscle in rats compared with the skewed protein distribution. Therefore, either the anabolic process and/or the experimental period could be the reasons for protein distribution not affecting sham muscles.

Key Takeaways

Sex and age were different between our animal and human studies. In particular, considering the age of participants, the data may imply that protein intake at breakfast is beneficial for preventing muscle atrophy, rather than the promotion of muscle hypertrophy, which is inferred from animal experiments. Skeletal muscle mass and strength decrease with age. Keep in mind that I the mice study it was just two meals a day, maybe the results would have been different if the meals were more evenly distributed in the time frame that has been shown to induce muscle protein synthesis every 4-5 hours.