Sarcopenic Obesity in Children: An Emerging Complication Evidenced by Clinical Data and a Juvenile Mouse Model.

BACKGROUND

Sarcopenic obesity (SO) is well-characterized in older adults, but its impact on muscle development in children remains poorly understood. This study investigated the effects of childhood obesity on musculoskeletal health and the underlying mechanisms.

METHODS

We enrolled 1447 children (31.4% girls; median age 11.10 years, IQR 9.39-12.50) for body composition assessment via dual-energy X-ray absorptiometry (DXA) and a separate cohort of 349 children (33.2% girls; median age 11.13 years, IQR 9.73-12.80) for grip strength measurement.

A juvenile mouse model of high-fat diet (HFD)-induced obesity was established and compared to an adult-onset model. Molecular pathways were examined via RNA sequencing and RT-qPCR.

Interventions included dietary reversal and vitamin C supplementation.

RESULTS

In children, the appendicular skeletal muscle mass ratio (ASMR) Z-score was inversely correlated with BMI-Z score (ρ = -0.369, p < 0.001) and body fat percentage (ρ = -0.668, p < 0.001). According to weight-specific reference criteria, most of children with obesity exhibited low grip strength (below the 25th percentile).

In mice, 4 weeks of HFD feeding in juveniles, but not adults, significantly reduced muscle mass (-6%, p < 0.05), muscle fibre diameter (-8%, p < 0.001), grip strength (-14%, p < 0.01) and rotarod performance (-29%, p < 0.05). RNA sequence and RT-qPCR revealed that HFD suppressed myogenic regulatory factors (e.g., Myod, Myog) and promoted adipogenic pathways specifically in juveniles.

In stark contrast, adult mice showed no such impairments after 4 weeks of HFD. The muscle deficits caused by juvenile obesity were not resolved but persisted even after subsequent dietary weight loss.

Vitamin C supplementation effectively mitigated HFD-induced impairments, increasing muscle fibre diameter (~15%, p < 0.001, vs. HFD), grip strength (~10%, p < 0.001, vs.

HFD) and expression of key myogenic genes (e.g., Myod, Myog, all p < 0.05).

CONCLUSIONS

Childhood obesity critically impairs muscle development during the juvenile growth period, driven by transcriptomic reprogramming that suppresses myogenesis. These deficits are persistent and not reversed by weight loss alone.

Vitamin C supplementation presents a potential therapeutic strategy to protect muscle health in children with obesity. The juvenile mouse model established herein provides a novel tool for future research into childhood SO.