456 TAK1-Mediated Signaling Regulates AMPK and Autophagy Pathways That Prevent Hepatic Steatosis and Hepatocarcinogenesis in Mice

Abstract

A S L D A b st ra ct s by mass spectrometry to diagnose NAFLD in overweight/ obese children. Methods: Patients were recruited from the Pediatric Preventive Cardiology and Metabolic Clinic. All patients were screened with an ultrasound of the abdomen to evaluate for the presence of NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube (SIFTMS) to identify new markers of NAFLD. Results: Sixty patients were included in the study (37 with NAFLD on ultrasound and 23 with normal liver). All children were overweight or obese with a body mass index ≥ 85% for age. The mean age was 15± 3.1 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD to those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. Discriminant analysis via stepwise variable selection of mass scanning ion peak data demonstrated five ion peaks that identified subjects with NAFLD with an accuracy of 90% (-2 log likelihood 0.172; Wilks' Lambda 0.145 (p , 0.0001)). Further analysis revealed that breath isoprene (cholesterol synthesis), acetone (glucose metabolism), trimethyamine (choline metabolism by microbiota), acetaldehyde (ethanol metabolism), and pentane (oxidative stress) were significantly higher in the NAFLD group compared to normal liver group, p value, 0.05 for all (Table). Conclusion: Exhaled breath analysis is a promising noninvasive method to detect fatty liver in obese children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes and pathways leading to the development of NAFLD. Future studies are needed to validate our findings.