Sex differences in MASLD and fitness improvement during a weight loss intervention for adolescents living with obesity.

Abstract

Background and aims: The interplay between liver and muscle health is incompletely understood, especially in adolescents living with obesity. Cardiopulmonary exercise testing (CPET) evaluates cardiorespiratory fitness through peak oxygen uptake ( O₂peak). The association of baseline cardiorespiratory fitness and metabolic dysfunction-associated steatotic liver disease (MASLD), and their longitudinal co-evolution during a lifestyle intervention, have not been studied in this population.

Methods: Adolescents with obesity receiving a lifestyle intervention in a residential setting were prospectively followed for 9 - 12 months. At baseline and after 6 months, MASLD was defined as a controlled-attenuation parameter ≥ 248dB/m. Cardiorespiratory fitness and body composition were assessed at the start and throughout the trajectory.

Results: 142 adolescents (69 boys) were included. Relative O₂peak was 37.9 (33.5 - 42.3) vs. 43.4 (39.7 - 49.8 ; p=0.004) mL∙kg^-1∙min^-1 [LM] in boys with and without MASLD, and respectively 36.3 (31.7 - 43.2) vs. 41.3 (34.8 - 46.2 ; p=0.055) mL∙kg^-1∙min^-1 [LM] in girls. Oxygen uptake efficiency slope (OUES) was respectively 40.6 (35.8 - 46.3) vs. 46.7 (41.6 - 53.8; p=0.011) in boys and 39.1 (34.7 - 45.1) vs. 44.2 (39.1 - 50.8 ; p=0.011) in girls. For boys with MASLD, initial relative O₂peak was the lowest for those with persistent MASLD during the lifestyle trajectory (33.5; 30.5 - 36.6 mL∙kg^-1∙min^-1 [LM]). During the lifestyle intervention, lean body mass (LM) was preserved in boys with MASLD resolution and girls without baseline MASLD, whereas boys with persistent MASLD and girls with baseline MASLD experienced LM losses of 7 - 9%.

Conclusion: Lower baseline cardiorespiratory fitness, independent from (fat) mass, is associated with (persistent) MASLD during a residential lifestyle intervention. LM preservation during weight loss trajectories, with concomitant improvement of maximal oxygen uptake, are important therapeutic targets.

Impact and implications: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common liver disease in children and adolescents worldwide. Although a better cardiorespiratory fitness at the start of a lifestyle intervention is linked with more weight loss, its association with cardiometabolic health and MASLD has not been assessed. A lower initial cardiorespiratory fitness was observed in adolescents with (persistent) MASLD, and in boys with an increased transient elastography. During the lifestyle intervention, boys and girls without MASLD or boys who experience MASLD resolution preserve their lean mass. Improvement of cardiorespiratory fitness and preservation of lean mass during a structured lifestyle intervention are important therapeutic targets, and sex-specific lifestyle interventions need to be developed and validated.