Thesis Defense Announcement
To:  The George Mason University Community

*Candidate: Thuy Phuong Tran
Program: Master of Science in Biology
*
*Date:   Monday March 4, 2013
Time:   1:00 p.m.
Place:  George Mason University, 
	    Prince William Campus <http://www.gmu.edu/resources/welcome/Directions-to-GMU.html>
	    Bull Run Hall, Room 253
*

*Title:  *"*Molecular Interactions of Polycystic Ovarian Syndrome (PCOS) 
With Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease (NAFLD)*"**

*Thesis Director*: *Dr. Ancha Baranova***

*Thesis Committee*:  *Dr. Daniel N. Cox and Dr. Alessandra Luchini
*A copy of the thesis will be available in the Johnson Center Library.  
All are invited to attend the defense.

*ABSTRACT *
Obesity is a common factor involved in both polycystic ovary syndrome 
(PCOS) and non-alcoholic fatty liver disease (NAFLD). Obesity causes 
NAFLD and aggravates hirsutism and menstrual disorder in polycystic 
ovary syndrome (PCOS).  Recent findings suggest that women with PCOS may 
be at risk for developing NAFLD and conversely, NAFLD patients may be a 
risk for PCOS.  To assess the literature for associations between PCOS 
and NAFLD at molecular level, we performed a systematic review of 
peer-reviewed articles related to PCOS and NAFLD. Articles were 
summarized and grouped according to different sections defining 
interactions of PCOS with metabolic syndrome and NAFLD as well as common 
risk factors, pathogenic pathways and treatment options.  Based on the 
association of PCOS and other metabolic abnormalities, such as insulin 
resistance, hyperandrogenism, obesity and NAFLD, the PCOS candidate 
genes have been proposed. Closer scrutiny of these genes placed most of 
their proteins at the crossroads of three highly inter- related 
conditions: metabolic syndrome, obesity and NAFLD.  This made us to 
postulate that PCOS is, in fact, the ovarian manifestation of metabolic 
syndrome, similarly to NAFLD that is currently recognized as the hepatic 
manifestation of metabolic syndrome. PCOS and NAFLD conditions may 
co-exist and may respond to similar therapeutic strategies.

In order to untangle the complex relationship between PCOS and NAFLD 
experimentally, we analyzed serum biomarkers of apoptosis, select 
adipokines and mRNA profile in the visceral adipose tissue of obese 
patients. Two clinical cohorts were compared: one with both PCOS and 
NAFLD that have not yet progressed to NASH according to their liver 
biopsies (N=12) and another, a BMI-matched non-PCOS non-NASH NAFLD 
control cohort (N=12). The total serum levels of apoptotic biomarker M30 
were significantly elevated in PCOS patients with liver steatosis as 
compared to non-PCOS NAFLD controls (P < 0.02), pointing that 
androgen-dependent proapoptotic PCOS environment may directly contribute 
to NAFLD progression in these patients. Similarly, hyperandrogenism may 
explain an observed PCOS-specific decrease (P < 0.04) in adipose LDLR 
mRNA expression that may be connected to the proneness of PCOS patients 
with concomitant liver disease to the progression to NASH. The levels of 
mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein 
were significantly increased in PCOS adipose (P < 0.007). In entire 
NAFLD cohort, the levels of the resistin were positively correlated with 
expression levels of LDLR and prothrombin time. In regards to all these 
parameters, the studies of larger cohorts of PCOS patients are needed, 
including subgroups without any histological sign of the liver disease 
and these without an excess of androgens.

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