Postmalnutrition weight gain is associated with changes to muscle and energy metabolism in adolescence: a cohort...

Treatment strategies for severe childhood malnutrition often encourage rapid weight gain and catch-up growth. However, the long-term metabolic consequences of such growth are unclear.

This study applied metabolomics to investigate how postmalnutrition weight gain (PMWG) in childhood relates to metabolic variation and physiological state in adolescence.

In an exploratory cohort study, urine and plasma were collected from adolescents (n = 151) 15 y after hospitalization for childhood malnutrition in Blantyre, Malawi. Analyses included untargeted urinary ¹H nuclear magnetic resonance spectroscopy, and targeted plasma liquid chromatography mass spectrometry-based metabolomics and myokine assay. PMWG was assessed using weight-for-age z-score (WAZ) at hospital discharge and 1-y follow-up from earlier studies. Adolescent physiology was measured, including muscle function [standing jump length (cm)]. Associations with PMWG were investigated using orthogonal projection to latent structures (OPLS) and regression models.

OPLS demonstrated that a greater increase in WAZ between discharge and 1-y postmalnutrition was associated with distinct plasma and urinary metabolic signatures in adolescence, especially among those with nonedematous malnutrition. This included higher fasting plasma sugars [β = 6.40 × 10³ μM; 95% confidence interval (CI): 2.99 × 10³, 9.81 × 10³], triglycerides, phosphatidylcholines, altered amino acids, and lower urinary muscle- and energy-related metabolites. Findings remained significant following adjustment (age, HIV, disability, sex, puberty, socioeconomic status, and minimum admission WAZ). In regression analyses, several of these metabolites positively associated with muscle outcomes, including creatinine (β = 13.5 cm; 95% CI: 7.87, 19.2) and β-hydroxy-β-methylbutyrate (β = 12.9 cm; 95% CI: 6.97, 18.7) with jump length.

Individuals with greater PMWG exhibited lower muscle-related metabolites and altered energy metabolism in adolescence. It remains unclear whether this reflects inherent differences in how individuals gain weight, or whether early-life weight gain programs future metabolic states. Elucidating these mechanisms will inform interventions to ameliorate long-term health risks, an urgent priority following the growing double burden of malnutrition in low- and middle-income countries.