Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism

American Journal of Physiology - Endocrinology and Metabolism - Tập 293 Số 6 - Trang E1552-E1563 - 2007
Pengxiang She1, Cynthia Van Horn, Tanya Reid, Susan M. Hutson, Robert N. Cooney, Christopher J. Lynch
1Dept. of Cellular and Molecular Physiology, MC-H166, Penn State Univ. College of Medicine, 500 University Dr., Hershey, PA 17033, USA.

Tóm tắt

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, we assessed the first two enzymatic steps, catalyzed by mitochondrial branched chain amino acid aminotransferase (BCATm) or the branched chain α-keto acid dehydrogenase (BCKD E1α subunit) complex, 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 E1α or BCKD kinase, in liver BCKD E1α 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 E1α. Plasma BCAAs were diminished by an overnight fast coinciding with dissipation of the changes in adipose tissue but not in liver. BCAAs also were reduced by surgical weight loss intervention (Roux-en-Y gastric bypass) in human subjects studied longitudinally. These changes coincided with increased BCATm and BCKD E1α 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 in muscle, may contribute to the rise in plasma BCAAs in obesity.

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American Journal of Physiology - Endocrinology and Metabolism

Tập 293 Số 6

E1552-E1563

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