Megan C Blair, Michael D Neinast, Cholsoon Jang, Qingwei Chu, Jae Woo Jung, Jessie Axsom, Marc R Bornstein, Chelsea Thorsheim, Kristina Li, Atsushi Hoshino, Steven Yang, Rachel J Roth Flach, Bei B Zhang, Joshua D Rabinowitz, Zoltan Arany
Elevated levels of plasma branched-chain amino acids (BCAAs) have been associated with insulin resistance and type 2 diabetes since the 1960s. Pharmacological activation of branched-chain α-ketoacid dehydrogenase (BCKDH), the rate-limiting enzyme of BCAA oxidation, lowers plasma BCAAs and improves insulin sensitivity. Here we show that modulation of BCKDH in skeletal muscle, but not liver, affects fasting plasma BCAAs in male mice. However, despite lowering BCAAs, increased BCAA oxidation in skeletal muscle does not improve insulin sensitivity...
April 2023: Nature metabolism