Branched-chain α-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.

Journal Article (Journal Article)

OBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched-chain α-keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6-month lifestyle-intervention program. METHODS: Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12-18 year) were analysed by flow-injection tandem MS and LC-MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA-IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables. RESULTS: Baseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI-metrics. Following lifestyle-intervention, α-keto-β-methylvalerate (α-KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA-IR at 6-month-follow-up. Glutamate/glutamine was positively associated with HOMA-IR at baseline and 6-month-follow-up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6-month-follow-up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight. CONCLUSIONS: BCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle-intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis.

Full Text

Duke Authors

Cited Authors

  • Gumus Balikcioglu, P; Jachthuber Trub, C; Balikcioglu, M; Ilkayeva, O; White, PJ; Muehlbauer, M; Bain, JR; Armstrong, S; Freemark, M

Published Date

  • January 2023

Published In

Volume / Issue

  • 6 / 1

Start / End Page

  • e388 -

PubMed ID

  • 36415168

Pubmed Central ID

  • PMC9836245

Electronic International Standard Serial Number (EISSN)

  • 2398-9238

Digital Object Identifier (DOI)

  • 10.1002/edm2.388


  • eng

Conference Location

  • England