1579-P: Altered Serum Ceramides as Part of Dyslipidemia in Adolescents with Metabolic Dysfunction–Associated Steatotic Liver Disease

Introduction & Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) in adults is associated with altered plasma ceramides, and may serve as liver metabolic biomarkers. However, less is known about whether similar changes are present in adolescents. We performed a lipidomic analysis to test whether adolescents with MASLD have altered plasma ceramides.

Methods: Plasma was acquired from boys and girls, 11-20y, classified as, 1) obese with biopsy-confirmed MASLD (n=44); 2) obese without MASLD (Ob, n=28); and 3) normal weight without MASLD (NW, n=29). MASLD patients had moderate to severe liver steatosis and 91% had ≥ stage 1 liver fibrosis.

Results: MASLD and Ob had similar body fat (45±7%), and were higher (p<0.01) than NW (31±6%). MASLD had higher triglycerides (p<0.01) than Ob and NW (199±110, 107±48, & 86±40 mg/dl, respectively) and had lower HDL-C than Ob or NW (40±10, 47±12, & 59±12 mg/dl respectively). Of the 6 major ceramide species measured, d18:1/24:0 was ~18% lower (p<0.001) in MASLD and Ob versus NW, while the others did not differ among groups. Of the 6 major dihydroceramide (dhCer) species measured, 4 were 32-185% higher (p<0.001) in the MASLD group versus the Ob and NW groups. The dhCer, but not the ceramide species, were positively correlated with trunk fat (r=0.34 to 0.55), but not with insulin resistance. dhCer 18:0/18:0, the most altered species, was positively correlated with liver steatosis (r=0.36), and along with 3 other dhCer species was positively correlated with MASLD Activity Score (r=0.35 to 0.41). There were no group differences in hexosylceramides, sphingosine, sphinganine, or the major sphingomyelins or dihydrosphingomyelins.

Conclusions: Similar to adults, adolescents with MASLD have altered plasma ceramides and dyslipidemia compared to NW and Ob peers without MASLD. The patterns observed suggest that ceramide flux may be elevated and ceramide-producing cells may be damaged in pediatric MASLD patients.