Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Morris Karmazyn

Abstract

Leptin and adiponectin are the adipokines that are shown to exert pro-hypertrophic and anti-hypertrophic effects respectively, in cardiomyocytes. We sought to determine the direct interaction between the adipocytes and cardiomyocytes during endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy and determine the role of leptin and adiponectin.

The adipose tissue conditioned medium (ACM) inhibited the ET-1-induced hypertrophy in a concentration-dependent manner and this anti-hypertrophic effect was more potent or reversed in the presence of leptin receptor antagonist (LRA; 0.1 nM) or adiponectin receptor-1 antibody (ARA; 100 ng/mL), respectively. ACM from heart failure rats induced by coronary artery ligation or obese rats did not mitigate the ET-1 induced hypertrophy in cardiomyocytes.

These studies demonstrate that the net anti-hypertrophic activity of ACM in ET-1-induced cardiac hypertrophy is likely mediated by adiponectin due activation of AMPK and determined by the leptin to adiponectin ratio. Heart failure and obese-induced pathology changes the characteristics of adipocytes although the underlying mechanisms for this effect are not completely known.


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