Bile Acids Contribute to the Gender-Biased Incidence of Hepatocellular Carcinoma

Basic Science Poster



Bile Acids Contribute to the Gender-Biased Incidence of Hepatocellular Carcinoma

Author/Presenter: Megan Patton
Co-Author(s): Sherwin Kelekar

The liver plays a fundamental role in regulating metabolic functions and bile acid synthesis is one of its salient features. The physiological concentration of bile acids is maintained by a negative feedback loop regulated by nuclear receptors Farnesoid X Receptor (Fxr) and Small Heterodimer Partner (Shp). When the genes encoding these two nuclear receptors are deleted from mice, they not only accumulate pathological levels of serum bile acids but also develop spontaneous liver carcinogenesis. Intriguingly, only the male mice develop spontaneous hepatocellular carcinoma whereas female mice do not, indicating a gender-specific predisposition. Clinical data strongly corroborates this gender-bias such that males have a higher susceptibility to developing hepatocellular carcinoma compared to females. Interestingly, we found that this predisposition strongly correlates with bile acid levels such that males accumulated twice the amount of serum bile acids compared to female mice. This data clearly indicates that the reduction in bile acids could mediate protection against hepatocellular carcinoma. We hope to (i) better understand the mechanism(s) that underlie the proliferative response to bile acids and (ii) elucidate the basis for the gender bias.

Author/Presenter Bio: Sherwin Kelekar is an academic hourly in the laboratory of Dr. Sayeepriyadarshini Anakk while Megan Patton is completing her senior year as an undergraduate in Molecular and Cellular Biology and also working in this lab. We both began working in Dr. Anakk’s laboratory in Spring of 2013 and are interested in pursuing academic medicine in the future.

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