Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes – published online 16/06/2021

Rasmus J. O. Sjögren, David Rizo-Roca, Alexander V. Chibalin, Elin Chorell, Regula Furrer, Shintaro Katayama, Jun Harada, Håkan K. R. Karlsson, Christoph Handschin, Thomas Moritz, Anna Krook, Erik Näslund, Juleen R. Zierath

Branched-chain amino acid (BCAA) metabolism is impaired in type 2 diabetes, as reflected by elevated circulating levels of leucine, isoleucine and valine. Since skeletal muscle is the largest contributor to systemic BCAA oxidation, perturbations in myocyte BCAA metabolism may impact whole-body metabolic homeostasis. In this issue, Sjögren, Rizo-Roca et al (https://doi.org/10.1007/s00125-021-05481-9) demonstrate that skeletal muscle BCAA catabolism in response to glucose loading is attenuated in type 2 diabetes, revealing that the metabolic inflexibility that characterises type 2 diabetes encompasses BCAA catabolism. Moreover, the authors identify oestrogen-related receptor α (ERRα) as an essential transcriptional partner of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in the regulation of the expression of the BCAA gene set in primary human myotubes. The authors state that these findings highlight the utility of an oral glucose tolerance test to unravel disturbances in both BCAA and glucose metabolism and provide insight into the development of new therapeutic strategies for the treatment of type 2 diabetes.

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