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Endocrine
Published in: Endocrine 1/2022

01-04-2022 | Insulins | Original Article

Excess branched-chain amino acids alter myotube metabolism and substrate preference which is worsened by concurrent insulin resistance

Authors: Madison E. Rivera, Caroline N. Rivera, Roger A. Vaughan

Published in: Endocrine | Issue 1/2022

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Abstract

Purpose

Branched-chain amino acids (BCAA) have been shown to enhance several cellular signaling pathways including protein synthesis and mitochondrial biogenesis, yet population data demonstrate a correlation between circulating BCAA and severity of insulin resistance which has been hypothesized to be, in part, a byproduct of BCAA inhibition of mitochondrial function. The purpose of this study is to examine the effect of a BCAA mixture on muscle metabolism and related gene expression in vitro.

Methods

C2C12 myotubes were treated with a BCAA mixture containing leucine:isoleucine:valine at a ratio of 2:1:1 at 0.2, 2, or 20 mM (based on leucine content) for 6 days. qRT-PCR was used to measure metabolic gene expression. Oxygen consumption and extracellular acidification were used to assess mitochondrial and glycolytic metabolism, respectively. Mitochondrial content was determined via mitochondrial-specific staining.

Results

Despite significantly elevated mitochondrial staining, 6-day BCAA treatment reduced basal mitochondrial metabolism at a supraphysiological concentration (20 mM) in both insulin sensitive and resistant cells. Peak mitochondrial capacity was also reduced in insulin-resistant (but not insulin sensitive) cells. Conversely, basal glycolytic metabolism was elevated following 20 mM BCAA treatment, regardless of insulin resistance. In addition, insulin-resistant cells treated with 20 mM BCAA exhibited reduced gene expression of Ppargc1a, Cytc, Atp5b, Glut4, and several glycolytic enzymes versus insulin sensitive cells treated with 20 mM BCAA.

Conclusions

Collectively, these findings suggest BCAA at supraphysiologically high levels may negatively alter mitochondrial metabolism, and concurrent insulin resistance may also diminish peak mitochondrial capacity, as well as impede molecular adaptations that support a transition to a glycolytic preference/compensation.
Appendix
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Metadata
Title
Excess branched-chain amino acids alter myotube metabolism and substrate preference which is worsened by concurrent insulin resistance
Authors
Madison E. Rivera
Caroline N. Rivera
Roger A. Vaughan
Publication date
01-04-2022
Publisher
Springer US
Keywords
Insulins
Insulins
Published in
Endocrine / Issue 1/2022
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-021-02939-z

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