Background: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. Methods: To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA-sequencing (RNA-seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents (Mage 16.9±0.4 yrs; BMI z-score 2.7±0.1) undergoing bariatric surgery and liver biopsy categorized into 3 groups; No steatosis (Normal, n=8), steatosis only (n=13), or NASH (n=10) by liver histology. Results: Age, body weight, and BMI did not differ among groups, but subjects with NASH were more insulin resistant (increased HOMA-IR, p<0.05 vs. other groups). RNA-seq revealed 175 up- and 492 down-regulated mRNA transcripts (≥ ± 1.5 fold; FDR <0.10) in IAT between NASH vs. Normal, with "Mitochondrial Dysfunction; p=4.19E-7" being the top regulated canonical pathway identified by Ingenuity Pathway Analysis; only 19 mRNA transcripts were up- and 148 down-regulated when comparing Steatosis vs. Normal, with suppression of "EIF2 Signaling: p=1.79E-27" being the top regulated pathway indicating increased cellular stress. A comparison of IAT between NASH vs. Steatosis found 515 up- and 175 down-regulated genes, with "Antigen Presentation; p=6.03E-18" being the top regulated canonical pathway and "Inflammatory Response" the top diseases and disorders function. Conclusions: Unique transcriptomic differences exist in IAT from severely obese adolescents with distinct stages of NAFLD, providing an important resource for identifying potential novel therapeutic targets for childhood NASH.
- childhood obesity
- visceral adipose tissue
- gene expression
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