title: Transcriptomic differences in intra-abdominal adipose tissue in extremely obese adolescents with different stages of NAFLD.
abstract: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. 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 [Mage16.9 ± 0.4 yr, body mass index (BMI) z-score 2.7 ± 0.1] undergoing bariatric surgery and liver biopsy categorized into three groups: no steatosis (normal, n = 8), steatosis only (n = 13), or NASH (n = 10) by liver histology. Age, body weight, and BMI did not differ among groups, but subjects with NASH were more insulin resistant (increased homeostatic model assessment/insulin resistance, P < 0.05 vs. other groups). RNA-Seq revealed 175 up- and 492 downregulated mRNA transcripts (≥±1.5-fold, false discovery rate <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 downregulated 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 downregulated genes, with "antigen presentation, P = 6.03E-18" being the top regulated canonical pathway and "inflammatory response" the top diseases and disorders function. 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.
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri.|Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Sheldon
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri.|Department of Medicine-Division of Gastroenterology and Hepatology University of Missouri, Columbia, Missouri.|Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Kanosky
authors.affiliation: Department of Animal Sciences, University of Missouri, Columbia, Missouri.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Wells
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Lili
authors.initials: L
authors.lastname: Miles
authors.affiliation: Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.|Department of Food Sciences, University of Missouri, Columbia, Missouri; and.
authors.forename: James W
authors.initials: JW
authors.lastname: Perfield
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Stavra
authors.initials: S
authors.lastname: Xanthakos
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Inge
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans Medical Center, Columbia, Missouri; rectors@health.missouri.edu.|Department of Medicine-Division of Gastroenterology and Hepatology University of Missouri, Columbia, Missouri.|Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D050110:Bariatric Surgery / Q000379:methods; D001706:Biopsy / Q000379:methods; D015992:Body Mass Index; D015536:Down-Regulation / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D059467:Transcriptome / Q000502:physiology*
chemical_list: D012333:RNA, Messenger
keywords: RNA-Seq; childhood obesity; gene expression; inflammation; transcriptome; visceral adipose tissue