Work

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

Year: 2025

Type: article

Abstract: Background 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. Objective To apply metabolomics to investigate how post-malnutrition weight gain (PMWG) in childhood relates to metabolic variation and physiological state in adolescence. Methods In an exploratory cohort study, urine and plasma were collected from adolescents ( n = 151) 15 years after hospitalization for childhood malnutrition in Blantyre, Malawi. Analyses included untargeted urinary 1 H nuclear magnetic resonance (NMR) spectroscopy, and targeted plasma liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and myokine assay. PMWG was assessed using weight-for-age z-score (WAZ) at hospital discharge and one-year 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. Results OPLS demonstrated that greater increase in WAZ between discharge to one-year post-malnutrition associated with distinct plasma and urinary metabolic signatures in adolescence, especially among those with non-edematous malnutrition. This included higher fasting plasma sugars (β = 6.40x10 3 μM; 95%CI 2.99 x10 3 : 9.81x10 3 ), 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, 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 HMB (β = 12.9 cm; 95%CI 6.97-18.7) with jump length. Conclusions 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.

Source: American Journal of Clinical Nutrition

DOI: 10.1016/j.ajcnut.2025.101130