Cardiac Hypertrophy Caused by Peroxisome Proliferator Activated Receptor-Gamma
Agonist Treatment Occurs Independently of Changes in Myocardial Insulin
Authors Sandra Sena, Isaac R. Rasmussen, Adam R. Wende, Alfred P. McQueen, Heather A.
Theobald, Nicole Wilde, Renata Oliveira Pereira, Sheldon E. Litwin, Joel P.
Berger, E. Dale Abel
Submitted By E. Dale Abel on 9/24/2007
Status Published
Journal Endocrinology
Year 2007
Date Published 12/1/2007
Volume : Pages 148(12) : 6047 - 6053
PubMed Reference 17823261
Abstract PPAR-gamma ligands are insulin sensitizers, widely used in the treatment of type
2 diabetes. A consistent observation in preclinical species is the development
of cardiac hypertrophy following short-term treatment with these agents. The
mechanisms for this hypertrophy are incompletely understood. Given the important
role of insulin signaling in the regulation of myocardial size, we tested the
hypothesis that augmentation of myocardial insulin signaling may play a role in
PPAR-gamma ligand-induced cardiac hypertrophy. We treated mice with
cardiomyocyte selective KO of insulin receptors (CIRKO) and littermate controls
(WT), with 2-(2-(4-phenoxy-
2-propylphenoxy) ethyl) indole-5-acetic acid, which is a non-thiazolidinedione
PPAR-gamma agonist (COOH) for 2 weeks. 2-weeks of COOH treatment increased heart
weights by 22% in CIRKO mice and by 16% in WT, and induced similar fold increase
in the expression of hypertrophic markers such as alpha-skeletal actin, BNP and
ANP in CIRKO and WT hearts. COOH treatment increased plasma volume by 10% in
COOH-treated WT and CIRKO mice, but did not increase systolic or diastolic blood
pressure. Echocardiographic analysis was also consistent with volume overload as
evidenced by increased LV diastolic diameters and cardiac output in COOH treated
CIRKO and WT mice. These data indicate that cardiac hypertrophy following
PPAR-gamma agonist treatment can occur in the absence of myocardial insulin
signaling and is likely secondary to the hemodynamic consequences of plasma
volume expansion.

Investigators with authorship
E. Dale AbelUniversity of Iowa


Pparaperoxisome proliferator activated receptor alpha
Ppargperoxisome proliferator activated receptor gamma