Michael D. Neinast

Oct 5, 2023 | cell.com | Marc R. Bornstein |Michael D. Neinast |Jessie E. Axsom |Chelsea L. Thorsheim

Highlights•Comprehensive isotope-tracer studies quantify cold-induced metabolic flux changes•BAT fuels TCA cycle flux with glucose during feeding and fatty acids during fasting•Pyruvate carboxylation is a major metabolic fate for glucose in BAT•Liver gluconeogenesis is required to maintain cold tolerance in fasted miceSummaryCold-induced thermogenesis (CIT) is widely studied as a potential avenue to treat obesity, but a thorough understanding of the metabolic changes driving CIT is lacking.

Apr 26, 2023 | nature.com | Michael D. Neinast |Cholsoon Jang |Jae Woo Jung |Jessie E. Axsom |Marc R. Bornstein |Chelsea L. Thorsheim | +4 more

AbstractElevated 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.