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

Abstract

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 alpha-keto acid dehydrogenase (BCKD E1alpha 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 E1alpha or BCKD kinase, in liver BCKD E1alpha 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 E1alpha. 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 E1alpha 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.

• Authors: Pengxiang She, Cynthia Van Horn, Tanya Reid, Susan M Hutson, Robert N Cooney, Christopher J Lynch
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 293 Issue 6 Pg. E1552-63 (Dec 2007) ISSN: 0193-1849 [Print] United States
• PMID: 17925455 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Amino Acids
• Amino Acids, Branched-Chain
• Keto Acids
• Minor Histocompatibility Antigens
• Pregnancy Proteins
• 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
• Transaminases
• BCAT2 protein, human
• branched-chain-amino-acid transaminase
• Leucine

Topics

• 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) (metabolism)
• Adipose Tissue (enzymology)
• Amino Acids (blood, metabolism)
• Amino Acids, Branched-Chain (blood, metabolism)
• Animals
• Bariatric Surgery
• Female
• Food Deprivation (physiology)
• Humans
• Keto Acids (blood, metabolism)
• Leucine (blood)
• Liver (enzymology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Minor Histocompatibility Antigens
• Muscle, Skeletal (enzymology)
• Obesity (blood, enzymology, physiopathology)
• Obesity, Morbid (blood, enzymology, surgery)
• Phosphorylation
• Pregnancy Proteins (metabolism)
• Rats
• Rats, Zucker
• Transaminases (metabolism)
• Weight Loss (physiology)