Lower fitness tied to persistent fatty liver disease in teen boys with obesity

Adolescent boys with obesity whose fatty liver disease persisted through a residential lifestyle program started out with markedly lower cardiorespiratory fitness and lost lean mass along the way, while girls showed a weaker link between fitness and liver outcomes, researchers from Ghent University in Belgium reported in JHEP Reports.

The prospective study included 142 adolescents ages 14 to 18 with severe obesity, 69 of them boys, admitted to the Zeepreventorium, a tertiary care rehabilitation center in De Haan, Belgium, that provides multidisciplinary pediatric obesity treatment. Participants were followed for nine to 12 months. Investigators measured liver fat with the controlled attenuation parameter (CAP) on transient elastography, defining metabolic dysfunction-associated steatotic liver disease (MASLD) as a CAP of 248 dB/m or higher. Fitness was assessed with cardiopulmonary exercise testing on a cycle ergometer, and body composition with DEXA scans.

Higher fitness at the start of a weight loss program has been linked with greater weight loss in adolescents, but its association with MASLD in this population had not been studied, the authors noted.

How fitness related to MASLD at baseline

At admission, 81.2% of boys and 54.8% of girls met the CAP threshold for MASLD. Because total body weight tends to understate fitness in people with obesity, the researchers expressed peak oxygen uptake relative to lean mass.

Boys with MASLD had a median relative peak oxygen uptake of 37.9 milliliters per kilogram of lean mass per minute, compared with 43.4 among boys without MASLD. Girls showed a similar gap (36.3 vs. 41.3), but it did not reach statistical significance. After adjustment for age and body mass index (BMI) z-score, each one-unit increase in relative peak oxygen uptake was associated with 14% lower odds of MASLD in boys, while the association in girls was not significant. A second fitness measure, the oxygen uptake efficiency slope, was significantly lower among both boys and girls with MASLD.

Which teens saw MASLD resolve

Six-month follow-up was available for 105 adolescents. Among the 76 who had MASLD at baseline, half achieved resolution.

In boys, baseline fitness separated the two groups. Boys whose MASLD persisted had a median relative peak oxygen uptake of 33.5, compared with 42.3 among boys whose disease resolved, and boys who achieved resolution had fitness levels similar to boys who never had MASLD. Each one-unit increase in relative peak oxygen uptake was tied to 46% higher adjusted odds of resolution in boys. In girls, baseline fitness did not differ by resolution status.

Lean mass loss during the lifestyle intervention

Body composition changes also split along MASLD status and sex. Lean mass was preserved in boys without baseline MASLD, boys whose MASLD resolved and girls without MASLD. Boys with persistent MASLD and girls with baseline MASLD, whether or not it resolved, lost 7% to 9% of their lean mass, without losing more total weight or achieving greater BMI z-score improvement than peers of the same sex.

Boys with persistent MASLD did post the largest gains in peak oxygen uptake, reaching levels comparable to the baseline fitness of boys without MASLD. The authors cautioned, however, that improvements in fitness expressed relative to body weight can reflect lean mass decline rather than true gains in oxygen uptake, particularly in girls.

The researchers proposed two phenotypes. One features absent or resolving MASLD, a more favorable metabolic profile, improving fitness and preserved lean mass. The other is marked by persistent MASLD and lean mass loss.

Pediatric MASLD burden and GLP-1 implications

MASLD is now the most common liver disease in children and adolescents worldwide, according to the authors. Between 50% and 70% of children with obesity have MASLD, and approximately 15% of those have advanced fibrosis or cirrhosis at diagnosis, according to research cited in the paper. In the United States, obesity prevalence among adolescents ages 12 to 19 was 22.2% from 2017 through March 2020, according to the Centers for Disease Control and Prevention.

“Further research on the optimal strategies for lean mass preservation during weight loss trajectories is needed, especially in the upcoming era of GLP-1 agonists, as lean mass loss of up to 25% to 40% has been reported,” the authors wrote. “Studies on cardiorespiratory fitness in adolescents with obesity should stratify and report their findings based on biological sex,” the researchers wrote.