AUTHOR=Abdualkader Abdualrahman Mohammed , Karwi Qutuba G. , Lopaschuk Gary D. , Al Batran Rami TITLE=The role of branched-chain amino acids and their downstream metabolites in mediating insulin resistance JOURNAL=Journal of Pharmacy & Pharmaceutical Sciences VOLUME=27 YEAR=2024 URL=https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences/articles/10.3389/jpps.2024.13040 DOI=10.3389/jpps.2024.13040 ISSN=1482-1826 ABSTRACT=

Elevated levels of circulating branched-chain amino acids (BCAAs) and their associated metabolites have been strongly linked to insulin resistance and type 2 diabetes. Despite extensive research, the precise mechanisms linking increased BCAA levels with these conditions remain elusive. In this review, we highlight the key organs involved in maintaining BCAA homeostasis and discuss how obesity and insulin resistance disrupt the intricate interplay among these organs, thus affecting BCAA balance. Additionally, we outline recent research shedding light on the impact of tissue-specific or systemic modulation of BCAA metabolism on circulating BCAA levels, their metabolites, and insulin sensitivity, while also identifying specific knowledge gaps and areas requiring further investigation. Finally, we summarize the effects of BCAA supplementation or restriction on obesity and insulin sensitivity.