Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-associated Steatotic Liver Disease: A Prospective Cohort Study.

To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program. In this prospective, cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4 to 6 months, anthropometric measurements, serum biochemical analysis, ultrasound and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration and hepatic IR by the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. 56% of 200 patients with obesity had evidence of steatosis on ultrasound and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already elevated in patients with only mild steatosis (p = 0.0403). Patients with more insulin-sensitive adipose tissue exhibited lower liver fat content (p < 0.05) and serum alanine transaminase levels (p = 0.001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (p < 0.001), but not with total body fat percentage (p = 0.263). After 4 to 6 months of lifestyle management, both MASLD and Adipo-IR improved. Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.

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Disclosures Work in the lab of AG and SL has received funding from Inventiva. All other authors do not declare any conflicts of interest.