Submitted on February 27, 2007
Accepted on October 4, 2007
Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched chain amino acid (BCAA) metabolism
Pengxiang She1, Cynthia Van Horn2, Tanya Reid2, Susan M Hutson2, Robert N. Cooney3, and Christopher J. Lynch1*
1 Cell & Mol Physiology, Pennsylvania State University, Hershey, Pennsylvania, United States
2 Biochemistry, Wake Forest University, Winston-Salem, North Carolina, United States
3 Department of Surgery, Pennsylvania State University College of Medicine, Hershey,, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: clynch{at}psu.edu.
Elevations in branched chain amino acids (BCAAs) in human obesity were first reported in the 1960s. Such reports are of interest because of the emerging role of BCAAs as potential regulators of satiety, leptin, glucose, cell signaling, adiposity and body weight (mTOR and PKC). To explore loss of catabolic capacity as a potential contributor to the obesity-related rises in BCAAs, the first two enzymatic steps catalyzed by mitochondrial branched chain amino acid aminotransferase (BCATm), branched chain 
-keto acid dehydrogenase (BCKD, E1 subunit) complex were assessed in two rodent models of obesity (ob/ob mice and Zucker rats) and after surgical weight loss intervention in humans. Obese rodents exhibited hyperaminoacidemia including BCAAs. Whereas no obesity-related changes were observed in rodent skeletal muscle BCATm, pS293 or total BCKD E1 or BCKD kinase, in liver, BCKD E1- was either unaltered or diminished by obesity, and pS293 (associated with the inactive state of BCKD) increased, along with BCKD kinase. In epididymal fat, obesity-related declines were observed in BCATm and BCKD E1. Plasma BCAAs were diminished by an overnight fast coinciding with dissipation of the changes in adipose tissue, but not liver. BCAAs were also reduced by surgical weight loss intervention (Roux-en-Y gastric bypass) in human subjects studied longitudinally. These changes coincided with increased BCATm and BCKD E1 in omental and subcutaneous fat. Our results are consistent with the idea that tissue specific alterations in BCAA metabolism, in liver and adipose tissue but not muscle, may contribute to the rise in plasma BCAAs in obesity.
