Energy metabolism profile of the effects of amino acid treatment on skeletal muscle cells: Leucine inhibits glycolysis of myotubes

Reiko Suzuki; Yoriko Sato; Kodwo Amuzuah Obeng; Daisuke Suzuki; Yusuke Komiya; Shin-Ichi Adachi; Fumiaki Yoshizawa; Yusuke Sato

doi:10.1016/j.nut.2020.110794

Energy metabolism profile of the effects of amino acid treatment on skeletal muscle cells: Leucine inhibits glycolysis of myotubes

Nutrition. 2020 Sep:77:110794. doi: 10.1016/j.nut.2020.110794. Epub 2020 Mar 6.

Authors

Reiko Suzuki¹, Yoriko Sato², Kodwo Amuzuah Obeng³, Daisuke Suzuki³, Yusuke Komiya⁴, Shin-Ichi Adachi², Fumiaki Yoshizawa⁵, Yusuke Sato⁶

Affiliations

¹ Department of Agrobiology and Bioresources, Utsunomiya University, Tochigi, Japan.
² Center for Bioscience Research and Education, Utsunomiya University, Tochigi, Japan United.
³ Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo, Japan.
⁴ Department of Animal Science, School of Veterinary Medicine, Kitasato University, Aomori, Japan.
⁵ Department of Agrobiology and Bioresources, Utsunomiya University, Tochigi, Japan; Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo, Japan.
⁶ Department of Agrobiology and Bioresources, Utsunomiya University, Tochigi, Japan; Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo, Japan. Electronic address: ysato@cc.utsunomiya-u.ac.jp.

PMID: 32417723
DOI: 10.1016/j.nut.2020.110794

Abstract

Objectives: Amino acids are not only components of proteins, but also can be metabolized to energy substances or be used as signaling molecules. However, basic knowledge of the relationship between amino acid treatment and energy metabolism is still insufficient. The aims of this study was to profile the effects of essential amino acid and alanine treatment on the energy metabolism of both myoblasts and myotubes and to contribute to the understanding of the basic relationship between amino acid treatment and energy metabolism of skeletal muscle cell.

Methods: We profiled whether amino acid (essential amino acids and alanine) treatment can affect the energy metabolism (glycolysis, mitochondrial respiration) of cultured skeletal muscle cells. C2C12 myoblasts and differentiated myotubes were treated with 5 mM each amino acid for 1 h, then the energy metabolism was measured by using extracellular flux analyzer.

Results: Although not all of the amino acid treatments could affect the energy metabolism of C2C12 myoblasts, leucine, isoleucine, lysine, phenylalanine, and histidine decreased the extracellular acidification rate, an indirect indicator of glycolysis, in differentiated myotubes without alteration of oxygen consumption rate, an indirect indicator of mitochondrial respiration. By glycolysis stress test, we found that leucine treatment inhibited glycolysis of myotubes when the substrate of glycolysis is sufficient in cultured media. The inhibitory effect of glycolysis by leucine was not canceled by rapamycin (an inhibitor for mTOR). But, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (an inhibitor for branched-chain α ketoacid dehydrogenase complex kinase) increased branched-chain amino acid catabolism, which decreased the glycolysis of myotubes.

Conclusion: Findings from the present study complemented the basic knowledge of amino acid treatment on the energy metabolism of cultured skeletal muscle cells and suggested the inhibitory effects of glycolysis by branched-chain amino acid catabolism.

Keywords: Amino acids; Energy metabolism; Glycolysis; Myoblasts; Myotubes.

MeSH terms

Amino Acids* / metabolism
Energy Metabolism
Glycolysis
Leucine
Muscle Fibers, Skeletal* / metabolism
Muscle, Skeletal / metabolism

Substances

Amino Acids
Leucine