Abstract P407: Decreased Peripheral Mitochondrial Respiration in Pre-Adolescent Hispanic Children With Hepatic Steatosis

Abstract

Introduction: Mitochondria plays a significant role in the functioning of the liver. Its function and structure have been associated with diseases outside the organelle by producing reactive oxygen species (ROS), causing generalized oxidative stress, improper function to several metabolic pathways, and perpetuating a pro-inflammatory state in conditions like obesity, diabetes, and metabolic dysfunction associated steatotic liver disease (MASLD). These diseases are on the rise and increase future atherosclerotic cardiovascular disease. Little is known regarding the pathophysiology of the earliest stages of hepatic steatosis, although mitochondrial dysfunction has been shown in later stages. In young children with and without MASLD, we aimed to measure mitochondrial respiration and compare it to hepatic steatosis and other cardiometabolic parameters. The hypothesis of the sub-study was that children with MASLD will have a decreased mitochondrial function compared with healthy children. Methods: We report data on 9 subjects, (all Latino subjects, mean age of 8.1 years, mean BMIp of 78%) who participated in screening for an ongoing clinical trial (ClinicalTrials No. NCT05292352). After consent and assent, procedures included drawing whole blood and transferring it immediately to the lab. Monocyte isolation was performed using RosetteSep™ Cocktail and measurement of fatty acid oxidation and glycolysis using the Seahorse Bioscience XFp extracellular flux analyzer. We measured the Oxygen Consumption Rate (OCR) as a proxy for mitochondrial respiration. Association with the mitochondrial parameters was evaluated with the percentage of hepatic steatosis (Hepafat), levels of ALT, insulin, and BMI percentile (BMIp). Data were analyzed using the R software program version 4.2.3 Results: Mean hepatic steatosis (HS) was 5.97% with a low of 2.4% and a high of 13%. The mean OCR for the subjects without MASLD (n=4, HS ≤5% by MRI) was 404.64 and the mean for subjects with MASLD (n=5, HS ≥5% by MRI) was 349.88. The mean OCR of subjects with a normal, overweight, and obese BMIp was 441.58, 397.45, 309.08, respectively. We found peripheral mitochondrial respiration tends to decrease as hepatic steatosis, BMIp, ALT and insulin levels increase. Conclusion: Hepatic steatosis is associated with decreased mitochondrial respiration and perhaps perpetuates an inflammatory state at very young ages in this vulnerable population. More subjects from the NAFLD prevention study will increase the significance of the study in the future.