Figure 5.

Patterns of altered BCAA metabolism observed in animal models of obesity. Losses of adipose tissue BCAA metabolic gene and protein expression in obesity have consistently been observed. In a rat model of diet-induced obesity,⁶³ reduced levels of BCAA metabolizing enzymes in adipose tissue seem to be compensated for by increased hepatic BCKDH activity¹⁶³ (termed a type B response). In contradistinction, hepatic BCKDH was also attenuated in other models such as ZDF rats,^161,162 Zucker fa/fa rats^72,73, ob/ob mice⁷² and Otsuka Long–Evans Tokushima Fatty rats¹⁶² (termed a type A response). Multiple peripheral tissues were examined and found to be affected in Zucker rats.⁷³ These distinct phenotypes are important because uncompensated loss of BCAA metabolism in multiple peripheral tissues could result in a higher range of plasma BCAAs that, when observed in states of obesity, associate to a greater extent with insulin resistance, levels of glycaemia and future T2DM. Alloisoleucine elevations below the level used to screen for MSUD have been proposed as a strategy to distinguish between these phenotypes.⁷⁵ Levels of BCAAs were considerably increased in models in which metabolism was impaired (↑↑). Abbreviations: BCAA, branched-chain amino acid; BCKDH, branched-chain α-keto acid dehydrogenase; MSUD, maple syrup urine disease. Adapted with permission from John Wiley and Sons © Olson, K. C. et al. Obesity (Silver Spring) 22, 1212–1215 (2014).⁷⁵