665 - Exploring the role of glycolysis in the pathogenesis of pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Different Ethnic Groups

Publication Number: 4651.665

Gloria J. Kang, Yale School of Medicine, West Haven, CT, United States; Nicola Santoro, Yale School of Medicine, New Haven, CT, United States; Jacopo Bonet, University of Padova, Padova, Veneto, Italy; Ermena Refugjati, Yale School of Medicine, Waterbury, CT, United States; Michelle Van Name, Yale School of Medicine, New Haven, CT, United States; Stephanie Samuels, Yale School of Medicine, New Haven, CT, United States; Sonia Caprio, Yale School of Medicine, New Haven, CT, United States

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) defines a clinical entity characterized by intrahepatic fat accumulation and metabolic dysfunctions (such as insulin resistance). It could result in various hepatic and cardio-metabolic complications and is observed to be pervasive even in youth. Also, ethnic differences in the occurrence of MASLD have been reported in adults and children. Hispanic obese youth show the highest prevalence of MALSD (~45%), while Non-Hispanic Black the lowest (~13%).

Objective: Main objective of the study to understand the mechanisms leading to the different susceptibility of developing MASLD in Non-Hispanic Black (NHB) and Hispanics (H) youths with obesity.

Design/Methods: 104 youths with obesity (mean age: 14.6±3.3, mean BMI z-score: 2.2±0.47) were recruited. The population included participants aged between 12 to 22 years, in puberty with a BMI >85th. Youths with MASLD were identified using abdominal Magnetic Resonance Imaging (MRI) by measuring liver proton density fat fraction (PDFF). >5.5% PDFF was considered MASLD. A 3-hour Oral Glucose Tolerance Test (OGTT) was used to measure plasma glucose, insulin, C-peptide, and lactate synthetic rate (LSR).

Results: Youths with MASLD showed higher glucose (P=0.002), Insulin (P=0.002), C-peptide (P= < 0.0001), and lactate production rate (LPR) (P=0.025) compared to youths without MASLD. There was a significant difference (P=0.019) in the LPR between Hispanic and Non-Hispanic Black youth without MASLD, despite the two groups showing overall degree of adiposity (BMI Z-score difference P=0.). Among those with MASLD, there was no difference in LPR between groups (P=0.385).

Conclusion(s): Youths with MASLD showed higher LPR probably due to higher rates of glycolytic activity or impaired oxidative phosphorylation. Higher conversion from glucose to lactate eventually leads to fatty acid synthesis through lipogenesis, possibly contributing to intrahepatic fat accumulation in youths. The significant difference in LPR between NHB and H without MASLD suggests that basal metabolism performs differently in these ethnic groups when MASLD is absent.

Changes in glucose (A), insulin (B), lactate (C), and lactate production rate (LPR) (D) during OGTT.
This figure illustrates the variations in glucose (A), insulin (B), lactate (C), and lactate production rate (LPR) (D) during an Oral Glucose Tolerance Test (OGTT) for youth with Metabolic Associated Steatotic Liver Disease (MASLD) compared to those without MASLD. Significantly higher levels of glucose (P=0.002), insulin (P=0.002), C-peptide (P= <0.0001), and LPR (P=0.025) are evident in the MASLD group, highlighting distinct metabolic responses to glucose intake.

Comparison of Lactate Production Rate (LPR) in Different Ethnic Groups.
This figure compares the basal metabolism, specifically the Lactate Production Rate (LPR), between Hispanic and Non-Hispanic Black youth without Metabolic Associated Steatotic Liver Disease (MASLD). The results show significant differences in LPR (P=0.019) between the two ethnic groups, indicating distinct metabolic variations.