Dataset Information

A branched-chain amino acid-based metabolic score can predict liver fat in children and adolescents with severe obesity.

ABSTRACT:

Background

Eighty percent of adolescents with severe obesity suffer from non-alcoholic fatty liver disease (NAFLD). Non-invasive prediction models have been tested in adults, however, they performed poorly in paediatric populations.

Objective

This study aimed to investigate novel biomarkers for NAFLD and to develop a score that predicts liver fat in youth with severe obesity.

Methods

From a population with a BMI >97th percentile aged 9-19 years (n = 68), clinically thoroughly characterized including MRI-derived proton density fat fraction (MRI-PDFF), amino acids and acylcarnitines were measured by HPLC-MS.

Results

In children with NAFLD, higher levels of plasma branched-chain amino acids (BCAA) were determined. BCAAs correlated with MRI-PDFF (R = 0.46, p < .01). We identified a linear regression model adjusted for age, sex and pubertal stage consisting of BCAAs, ALT, GGT, ferritin and insulin that predicted MRI-PDFF (R = 0.75, p < .01). ROC analysis of this model revealed AUCs of 0.85, 0.85 and 0.92 for the detection of any, moderate and severe steatosis, respectively, thus markedly outperforming previously published scores.

Conclusion

BCAAs could be an important link between obesity and other metabolic pathways. A BCAA-based metabolic score can predict steatosis grade in high-risk children and adolescents and may provide a feasible alternative to sophisticated methods like MRI or biopsy in the future.

SUBMITTER: Lischka J

PROVIDER: S-EPMC7988615 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:UnlabelledWhat is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index.BackgroundBranched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children.ObjectiveTo determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance.MethodsSixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data).ResultsElevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046).ConclusionsElevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance.