| First Author | Shin AC | Year | 2014 |
| Journal | Cell Metab | Volume | 20 |
| Issue | 5 | Pages | 898-909 |
| PubMed ID | 25307860 | Mgi Jnum | J:218411 |
| Mgi Id | MGI:5617435 | Doi | 10.1016/j.cmet.2014.09.003 |
| Citation | Shin AC, et al. (2014) Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism. Cell Metab 20(5):898-909 |
| abstractText | Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain alpha-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes. |
