S1090 Exploring the Role of Choline and Phospholipids in Pediatric Nonalcoholic Fatty Liver Disease

Introduction: The pathophysiology of nonalcoholic fatty liver disease (NAFLD) is incompletely understood but may involve dysregulated triglyceride (TG) processing. Our study focused on choline metabolism and its role in phospholipid synthesis in very low-density lipoproteins (VLDL) production as a vehicle to export TG from the hepatocyte. We designed a prospective translational pilot study to assess choline metabolism in pediatric patients with NAFLD through use of lipidomics in these subjects. Methods: We recruited obese or overweight children with risk factors for metabolic syndrome with and without NAFLD and 10 healthy controls. NAFLD was diagnosed based on imaging (ultrasonography or elastography) or ALT level ( > 52 u/L for males or > 44 u/L for females) and after ruling out other causes of chronic liver disease. We measured serum choline, carnitine, betaine, trimethylamine N-oxide (TMAO), a byproduct of dietary choline gut microbial metabolism, and lipidomic profile for plasma lysophosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species in all participating subjects. Results: BMI and dyslipidemia prevalence were significantly higher in NAFLD compared to non-NAFLD and healthy controls. Serum choline, carnitine and betaine were not different between the study groups. TMAO was significantly higher in NAFLD vs non-NAFLD subjects 1.9 [1.4, 3.4] vs 1.3 [0.95, 2.0] µM (p = 0.034). After adjusting for sex, BMI z-score, VLDL, LDL, and HDL , lipidomics analysis showed that all PC species were higher in obese patients (NAFLD and non NAFLD) compared to healthy controls 2315.5 (2105.9, 2546.0) , 2218.9 (2064.3, 2385.1) vs 1559.5 (1241.6, 1958.9) ng/uL (p=0.024). Several PC species were higher including (32:1, 32:2, 34:3, 34:4, 34:5, 36:1, 36:2, 36:5, and 38:6). We also noted that LPC 20:5 was higher in obese subjects (5.1, 4.7 vs 1.7) p=0.026. None of the PE and LPE species were different between the three groups. No significant difference in PC, LPC, PE and LPE was noted between NAFLD and non NAFLD subjects. Conclusion: PC species are increased in NAFLD and non NAFLD subjects compared to healthy controls. This can be explained by obesity’s effect on PC metabolism. Even though TMAO was higher among NAFLD compared to non-NAFLD subjects, PC species were not different between the two groups. This may be explained by either upregulation of endogenous choline synthesis or small sample size.