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
	    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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