2013
DOI: 10.1371/journal.pone.0059443
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Leucine and Protein Metabolism in Obese Zucker Rats

Abstract: Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW,… Show more

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Cited by 92 publications
(115 citation statements)
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References 91 publications
(145 reference statements)
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“…Insulin is the chief regulator of amino acid metabolism and changes in fasting BCAA levels may be regulated by the effect of insulin on the rate of appearance and clearance of BCAA together with a decreased activity of catabolic enzymes [2]. Loss-of-function mutations in PPM1K in humans [21], and disruption of key BCAA metabolism in obese mice and Zucker rats, exhibit a reduced expression of the mitochondrial isoform of branched chain-amino-acid transaminase (BCAT2; which catalyses the first and reversible step in BCAA catabolism), and mitochondrial branched chain α-keto acid dehydrogenase (BCKD) complex E1-α (which catalyses the rate-controlling and the first irreversible step), leading to increased plasma BCAA levels [22,23]. A decreased BCAA metabolism in fat tissue may contribute to higher BCAA levels in individuals with insulin-resistant obesity [2,[22][23][24].…”
Section: Discussionmentioning
confidence: 99%
“…Insulin is the chief regulator of amino acid metabolism and changes in fasting BCAA levels may be regulated by the effect of insulin on the rate of appearance and clearance of BCAA together with a decreased activity of catabolic enzymes [2]. Loss-of-function mutations in PPM1K in humans [21], and disruption of key BCAA metabolism in obese mice and Zucker rats, exhibit a reduced expression of the mitochondrial isoform of branched chain-amino-acid transaminase (BCAT2; which catalyses the first and reversible step in BCAA catabolism), and mitochondrial branched chain α-keto acid dehydrogenase (BCKD) complex E1-α (which catalyses the rate-controlling and the first irreversible step), leading to increased plasma BCAA levels [22,23]. A decreased BCAA metabolism in fat tissue may contribute to higher BCAA levels in individuals with insulin-resistant obesity [2,[22][23][24].…”
Section: Discussionmentioning
confidence: 99%
“…Concentrations of BCAA and total amino acids in whole body were measured using high performance liquid chromatography (HPLC) as described previously (14). Concentrations of amino acids in whole brain were analyzed by Kristine C. Olson under the supervision of Dr. Christopher J. Lynch (15). Free amino acids were pre-column-derivatized using Phenomenex EZ-fast reagent and analyzed by ultra performance liquid chromatography-MS using a Waters Synapt HDMS hybrid quantitative TOF with ion mobility, located at the Pennsylvania State College of Medicine Macromolecular Core Facility.…”
Section: Methodsmentioning
confidence: 99%
“…Both gene expression and protein concentration of enzymes involved in BCAA catabolism have been shown repeatedly to be blunted on VAT of obese individuals [21] and animal models [7,22], at least those genetically modified. In the present study, the BCAA transamination capacity of VAT and SCAT increased significantly with the obesity phenotype induced by the HFHS.…”
Section: Fasting Metabolism Of Bcaa and Relation To The Ir Phenotypementioning
confidence: 99%