Relationship between protein intake time and muscle mass increase Relationship between protein intake time and muscle mass increase

Morning protein intake timing according to the body clock is effective for increasing muscle mass

Announcement points

Shinya Aoyama, Assistant Professor, Graduate School of Biomedical Sciences, Nagasaki University (Deputy Researcher, Priority Area Research Organization, Waseda University, 2015-2019) and Professor Shigenobu Shibata, Faculty of Science and Engineering, Waseda University , A research group led by Professor Kim Hyun-ki has recently clarified that the timing of protein intake has an effect on the muscle mass-increasing effect.

It is known that dietary protein is important for skeletal muscle synthesis and maintenance / increase of muscle mass. So far, there have been many unclear points. This research group found that the body clock of muscles (circadian clock ^{* 1} for about 24 hours per cycle) is important for obtaining the effect of increasing muscle mass, and not only the daily intake of protein but also the daily intake of protein. , It was clarified that the timing of ingestion is also important (Fig. 1). Since protein intake according to the body clock is effective for increasing muscle mass, by making good use of this intake timing, the health of elderly people who tend to lose muscle strength and muscle mass is efficiently maintained and promoted. It may be possible.

This research result was published in the online version of the open access journal "Cell Reports" published by Cell Press, USA on July 6, 2021 (Tuesday) at 11:00 AM (Eastern Time).

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

(1) What was known from previous research

Dietary protein is said to be important for skeletal muscle synthesis and maintenance / increase of muscle mass. From dietary surveys in each country, it is known that in many countries, protein intake is low in breakfast, and that intake is biased among the three meals of morning, lunch, and supper. Epidemiological studies have shown that dietary bias during the day is related to skeletal muscle function, but what happens not only in the morning shortage but also in the evening shortage? There were many unclear points about the details.

(2) What was newly realized and clarified in this research

In this study, we conducted animal experiments using mice and found that different time zones of protein intake during the day affect the increase in muscle mass due to overload ^{* 2} . In addition, we focused on the clock gene that controls the biological clock as a key factor that produces the difference in the effect depending on the intake time of protein, and analyzed the involvement of the biological clock in the muscle mass increasing effect depending on the intake timing. In addition, a human study investigated the relationship between protein intake in three meals and muscle strength and mass.

① Protein intake timing affects muscle mass increase

Mice are bred under the condition of two meals a day (Fig. 2, the food after waking up is defined as breakfast and the food before bedtime is defined as supper), and the total protein intake per day is adjusted, and the protein content of each meal is adjusted. When changed, the increase in muscle mass was promoted in the mice that ingested a large amount of protein for breakfast compared to the mice that ingested a large amount in the dinner and the mice that ingested evenly in the morning and dinner (Fig. 2, right). If the daily protein intake is the same, it is shown that intensive intake in the morning (beginning of the active period) is more effective in increasing muscle mass.

(2) Branched-chain amino acids are involved in increasing muscle mass due to protein intake at breakfast

Branched-chain amino acids ^{* 3} are known to have a strong effect on enhancing muscle synthesis. Therefore, in order to clarify whether the branched-chain amino acids contained in the protein are involved in the muscle mass-increasing effect of protein intake at breakfast, mice are bred under the condition of two meals a day as before, and breakfast is performed. Or, I measured the muscle mass when I fed a branched-chain amino acid-added diet for breakfast. As a result, it was found that the intake of the branched-chain amino acid-added diet for breakfast is more likely to increase muscle mass than the intake for dinner. Such an ingestion effect at breakfast was not seen in the diet containing other amino acids (amino acids other than the branched chain amino acids contained in casein ^{* 4} , which is the protein source of the diet). This suggests that branched-chain amino acids play a major role in increasing muscle mass due to protein intake at breakfast.

③ Muscle mass increase due to protein intake timing is caused through the body clock

In order to elucidate the mechanism why intake in the morning (early active period) tends to increase muscle mass, this research group focused on a circadian clock (body clock) with a cycle of about 24 hours. The biological clock that exists in various cells throughout the body is composed of dozens of genes called clock genes, and gives various physiological functions a day-night rhythm. This research group suspected that this clock gene causes chronotypes of physiological functions such as absorption and metabolism of nutrients, and that the muscle mass-increasing effect is produced by the timing of protein and amino acid intake. Therefore, we measured protein intake patterns and muscle mass for breakfast and dinner using Clock mutant mice with a mutation in the clock gene Clock and muscle-specific Bmal1-deficient mice lacking the clock gene Bmal1 in muscles. As a result of the analysis, it was clarified that the muscle mass-increasing effect of breakfast protein intake was not observed in these mice, and that the muscle body clock was involved in the muscle mass-increasing effect depending on the intake timing (Fig. 3).

④ In elderly women, the protein intake ratio at breakfast shows a positive correlation with muscle function.

We investigated the relationship between protein intake in three meals and skeletal muscle function in elderly women. As a result, compared to humans who consume a large amount of protein at dinner, humans who consume a large amount of protein at breakfast have a higher skeletal muscle index ^{* 5} and grip, and at breakfast for daily protein intake. It was found that the ratio of protein intake and the skeletal muscle index showed a positive correlation (Fig. 4). Although the causal relationship is still unclear because it is an observational study, it has been shown that morning protein may be effective in maintaining and increasing muscle mass even in humans.

(3) Spillover and social impact of research

From the results of this study that the body clock is important for the muscle mass-increasing effect of protein intake in the morning (beginning of the active period), it is possible that protein intake according to the body clock is effective for muscle mass increase. On the other hand, if you have a lifestyle rhythm that disturbs your body clock, such as night shift work, shift work, or skipping breakfast, you may not be able to benefit from the increase in muscle mass due to protein intake at breakfast. In addition, although additional verification is required, it may be possible to efficiently maintain and improve the health of the elderly, who tend to lose muscle strength and muscle mass, by making good use of not only the amount of protein but also the timing of intake.

(4) Future issues

It is necessary to elucidate the molecular mechanism by which clock genes actually produce the effect of protein intake timing, and the effectiveness of breakfast protein intake by intervention studies in humans. There are still many challenges.

(5) Researcher's comments

In this study, it was shown that the timing of protein intake is important for increasing muscle mass, and that the intake effect in the morning (beginning of the active period) is particularly high. However, dietary surveys in many countries show that breakfast protein intake is low and prone to deficiency. In the future, in order to promote protein intake for breakfast, it is desirable to develop a protein-rich menu that is easy to consume even at breakfast.

(6) Glossary

* 1 Circadian clock A system that controls chronotypes of various functions of the living body such as sleep / wakefulness and body temperature. Clock genes such as Clock and Bmal1 work to keep a rhythm of about 24 hours. Circadian clocks are also involved in chronotypes such as digestion and absorption of nutrients and metabolism.

* 2 A model that induces muscle hypertrophy by overloading the plantaris muscle by partial excision of the overloaded collaborative muscles (soleus muscle and gastrocnemius muscle).

* 3 Branched-chain amino acids A general term for amino acids that have a structure branched into the side chain, including valine, leucine, and isoleucine.

* 4 Casein A protein that accounts for most of the protein in milk. A protein source often used in research feeds in the field of nutrition.

* 5 Skeletal muscle index The value (kg / m2) obtained by dividing the muscle mass (kg) of the limbs by the square of the height (m). It is used as an index of skeletal muscle mass.

(7) Research grant

Research fund name: SIP (Strategic Innovation Creation Program) "Next-generation agriculture, forestry and fisheries creation technology" Research project name: Development of next-generation food and exercise recipes based on time nutrition and exercise in consideration of the elderly Research representative name ( Affiliation name): Shigenobu Shibata (Waseda University)

Research fund name: Future society creation project (self-management based on elucidation of the mechanism of action of daily activities such as food, exercise, sleep) Research project name: Creation of personal health management system from the viewpoint of time nutrition Research representative name (affiliation name) ): Shigenobu Shibata (Waseda University)

Research Fund Name: Scientific Research Fund Young Research Project Name: Elucidation of the molecular mechanism by which protein deficiency in breakfast suppresses muscle hypertrophy Research representative name (affiliation name): Shinya Aoyama (Nagasaki University)

Research Fund Name: Japan Society for Nutrition and Food Science Nutrition and Food Science Fund Young Researcher Grant Research Project Name: Analysis of the molecular mechanism by which the time pattern of protein intake regulates muscle mass Research representative name (affiliation name): Shinya Aoyama (Affiliation name) Nagasaki University)

(8) Paper information

Journal name: Cell Reports Paper name: Distribution of dietary protein intake in daily meals influences skeletal muscle hypertrophy via the muscle clock Author name (affiliation name): Shinya Aoyama ^{1,2 #} , Hyeon-Ki Kim ^{1 #} ,, Masaki Takahashi ³ , Yu Tahara ¹ , Shigeki Shimiba ⁴ , Rina Hirooka ⁵ , Mizuho Tanaka ⁵ , Takeru Shimoda ⁵ , Hanako Chijiki ⁵ , Shuichi Kojima ⁵ , Keisuke Sasaki ⁵ , Kengo Takahashi ⁵ , Saneyuki Makino ⁵ , Miku Takizawa ⁵ , Kazuyuki Shinohara ² , Shigenobu Shibata ^{1 *} (Shinya Aoyama ^{1,2 #} , Motoki Kinho ^{1 #} , Masaki Takahashi ³ , Yu Tahara ¹ , Shigeki Shinba ⁴ , Rina Hirooka ⁵ , Mizuho Tanaka ⁵ , Taketaka Shimoda ⁵ , Hanako Chichiki ⁵ , Shuichi Kojima ⁵ , Keisuke Sasaki ⁵ , Kengo Takahashi ⁵ , Masayuki Makino ⁵ , Miku Takizawa ⁵ , Kazuyuki Shinohara ² , Shigenobu Shibata ^{1 *} )

Affiliation name: 1: Waseda University Faculty of Science and Engineering 2: Nagasaki University School of Medicine Neurofunctionality 3: Tokyo Institute of Technology Liberal Arts Research and Education Institute 4: Nihon University Faculty of Pharmacy 5: Waseda University Graduate School of Advanced Science and Engineering

^#First author, * Responsible author

Publication date (Eastern time): July 6, 2021 (Tuesday) 11:00 AM Publication date (Japan time): July 7, 2021 (Wednesday) 1:00 AM DOI: https://doi.org/10.1016/ j.celrep.2021.109336