> Dissertation Defense Announcement > To: The George Mason University Community > > Candidate: David L. Armistead > Program: PhD Biosciences > > Date: Thursday June 7, 2012 > Time: 11:00 a.m. > Place: George Mason University > Research Hall, Room #161 > Fairfax Campus <http://www.gmu.edu/resources/visitors/> > > Dissertation Director/Committee Chair: Dr. Ancha Baranova > Committee members: Dr. Zobair Younossi, Dr. Vikas Chandhoke, Dr. > Patrick Gillevet > Title: "Differential Expression of microRNAs in the Visceral Adipose > of Patients with NASH, Pericellular Fibrosis and Type II Diabetes" > > The dissertation is on reserve in the Johnson Center Library, Fairfax > campus. > The doctoral project will not be read at the meeting, but should be > read in advance. > > All members of the George Mason University community are invited to > attend. > > > *ABSTRACT:* > > Non-alcoholic steatohepatitis (NASH) is the progressive form of > non-alcoholic fatty liver disease (NAFLD). NASH is one of the least > understood metabolic consequences of obesity. The dysregulation of > visceral adipose derived signaling molecules, including adipokines, > oxidative stressors and cytokines is associated with the progression > of NAFLD. MicroRNAs (miRNAs) represent a new class of > post-transcriptional regulators of gene expression. These non-coding > single stranded molecules are predicted to regulate a third of all > human genes as they interact with certain recognition motifs found > within the 3' un-translated region (UTR) of protein coding mRNAs. > These interactions ultimately down regulate gene expression through > mechanisms of translational repression, mRNA destabilization > --mediated repression or direct mRNA degradation. In this study we > profiled 664 mature miRNAs derived from the visceral white adipose > tissue (WAT) of morbidly obese patients with NASH and non-NASH NAFLD. > A global down-regulation of 84 mature miRNAs (Fold Change > -1.7 and > P- < 0.05) was observed in patients with NASH when compared to > non-NASH NAFLD controls. A total of 54 adipose derived mature miRNAs > (Fold Change > -1.7 and P- < 0.05) were differentially expressed in > NASH patients with pericellular fibrosis when compared to non-NASH > NAFLD controls. Additionally, 6 primary transcript miRNA (pri-miRNA) > assays were designed and tested for locus specific NASH related > transcription. Of these, a single primary miRNA transcript, miR-7-1 ( > Fold Change > 1.7 and P -- < 0.01) was found to be up-regulated in > NASH vs. Non-NASH NAFLD. Lastly, a systems biology analysis of NASH > related miRNAs was performed to better elucidate orchestrated > communication between visceral WAT and the liver, as well as the > hepatic consequences of obesity related adipose remodeling. The > results from our ontology enrichment analysis clearly associate a > global downregulation of adipose specific miRNAs with hepatocellular > carcinoma, liver neoplasms as well as chronic liver disease. > Furthermore, our systems biology analysis revealed that NASH related > adipose derived miRNA expression is associated with the dysegulation > of the peroxisome proliferator-activated receptor (PPAR) pathway, > inflammation pathways and may be associated with adiponectin reduced > AMP-activated protein kinase (AMPK) signaling in the liver. This is > the first study to our knowledge which links the deregulation of WAT > miRNA expression and the progression of NAFLD. > > ### >