Almaw, Naredos; Chaudhuri, Dipayan (University of Utah)
Faculty Advisor: Chaudhuri, Dipayan (School of Medicine, Internal Medicine)
Fibroblast Growth Factor 21 (FGF21), a regulator of metabolism that is typically expressed in the liver, has recently been shown to be induced by other tissues in the body as a response to mitochondrial stress. Elevated levels of serum FGF21 was exhibited in children with mitochondrial mutation-induced mitochondrial dysfunctions. Similarly, in dilated cardiomyopathy, a common type of heart failure (HF) mitochondrial dysfunction is associated with mitochondrial DNA damage. This study aims to determine the signaling pathway that leads to the production and effects of FGF21 during mitochondrial dysfunction associated HF. We hypothesize that in left ventricular failure, cardiomyocytes experience oxidative stress, which initiates signaling pathways that leads to the production of FGF21 by other organs.
To test this hypothesis, HF was induced in four mice models via Transverse Aortic Constriction (TAC), and tissue samples were collected. Messenger RNA (mRNA) was extracted, and quantitative Polymerase Chain Reaction (qPCR) was performed to examine the FGF21 gene expression in control and experiment mice models. The qPCR data showed an upregulation of FGF21 in the heart, liver, and pancreas of experiment mice. qPCR results were confirmed through FGF21 protein expression via western blot. Our preliminary results appear to support our hypothesis that during heart failure, the heart sends stress signals to other organs to produce FGF21. Understanding the origin of FGF21 production could help better understand the critical role it plays in preventing disease progression in HF patients.