title: Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).
abstract: BACKGROUND
  Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only.
  
  
  METHODS
  We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann-Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed.
  
  
  RESULTS
  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 that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT).
  
  
  CONCLUSIONS
  An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed under conditions associated with insulin resistance, including PCOS. The studies of larger cohorts of NAFLD with and without PCOS patients are needed to further assess these potential interactions.
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA.
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.forename: Thuy Phuong
authors.initials: TP
authors.lastname: Tran
authors.forename: Arian
authors.initials: A
authors.lastname: Afendy
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Shamsaddini
authors.forename: Rohini
authors.initials: R
authors.lastname: Mehta
authors.forename: Vikas
authors.initials: V
authors.lastname: Chandhoke
authors.forename: Aybike
authors.initials: A
authors.lastname: Birerdinc
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000728:Androgens / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018450:Disease Progression; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D053538:Keratin-18 / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009687:Nuclear Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D012044:Regression Analysis; D052243:Resistin / Q000378:metabolism
chemical_list: D054392:Adipokines; D000728:Androgens; D015415:Biomarkers; D003598:Cytoskeletal Proteins; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; C512806:NIN protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011973:Receptors, LDL; D052243:Resistin