> 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
> 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
> 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.