Molecular signature of adipose tissue in patients with both Non-Alcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovarian Syndrome (PCOS)

Abstract

BackgroundPolycystic 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.MethodsWe 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.ResultsThe 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).ConclusionAn 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.

Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

“…These data are in agreement with previous reports that suggest that the intrauterine environment plays an important role in the development of both NAFLD and PCOS during postnatal life (Baranova et al 2013, Brumbaugh & Friedman 2014.…”

The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet

“…Leptin levels are reportedly higher in obese individuals with nonalcoholic fatty liver disease [18], [19]. Similarly, in the present study, leptin levels in the HFD group were higher than those in the CON group, and GBx treatment significantly attenuated the HFD-induced increase in serum leptin levels.…”

Identification of quantitative trait loci and candidate genes for an anxiolytic‐like response to ethanol in BXD recombinant inbred strains

“…In the brain, Nin is known to function as a microtubule binding protein and an important regulator of neocortical axonal outgrowth and branching (Bouckson‐Castaing et al ; Mogensen et al ; Srivatsa et al ). Recent studies have reported an association between genetic variation within the Nin gene or altered expression patterns of Nin with a number of diseases and genetic disorders, including breast cancer (Olson et al ), a type of skeletal dysplasia (Grosch et al ), microcephalic primordial dwarfism (Dauber et al ), polycystic ovary syndrome and non‐alcoholic fatty liver disease (Baranova et al ). This suggests that certain genetic variants of Nin might be a risk factor for multiple disease phenotypes.…”