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metabolism (
Chiu et al., 2001, 2005; Son et al., 2007; Zimmermann et al., 2004
),
while other transgenic models display similar amounts of cardiomyocyte LDs but
are free of cardiac function abnormalities (
Liu et al., 2007; Pollak et al., 2013;
Wang et al., 2013
). Overall, it is clear that development of cardiac tissue lipotoxi-
city/dysfunction is not due to the simple presence of ectopic fat in this tissue but
rather due to alterations in LD function as they attempt to manage appropriately ex-
cess energy. This has also been shown clinically by the recent observation that myo-
cardium from patients with dilated cardiomyopathy has decreased cardiac
triglycerides (TG) but increased diacylglycerols and ceramides, implied defects in
cardiac LD packaging associated with human heart failure (
Chokshi et al., 2012
).
Directly examining cardiomyocyte LD function will address the nature of link(s) be-
tween excess cardiomyocyte LDs, LD dysfunction, and disease state.
LDs are now recognized as bona fide cellular organelles, and work supporting
their importance in cellular and whole body energy homeostasis has been recently
reviewed (
Coen & Goodpaster, 2012; Greenberg et al., 2011
). They are composed
of a core of neutral esterified lipids, uniquely surrounded by a monolayer of phos-
pholipids where LD-associated proteins dock and regulate the LD function. LD bio-
genesis is a fundamental cellular function; most mammalian cells store nonesterified
fatty acid (NEFA) as triglyceride (TG) in LDs when grown in the presence of FA
(
Listenberger et al., 2003
). LD accumulation in “normal” cells maintains low intra-
cellular NEFA levels but sufficient for essential purposes, for example, beta-
oxidation, membrane phospholipid synthesis, and steroid production, depending
on cell type and developmental state. Cardiac and skeletal muscle cells mainly
use NEFA for energy, while liver uses them for very low density lipoprotein produc-
tion, mammary epithelial cells for milk production, and specialized lung cells make
surfactant. These cell-specific uses imply that the LD compartment where TG accu-
mulates must be highly dynamic, absorbing excess NEFA and releasing NEFA to
accommodate individual cell requirements. Thus, the LD compartment interacts with
other cellular compartments where TG is formed (presumably endoplasmic reticu-
lum, ER) and where NEFA is utilized (cytosol, mitochondria, endosomes).
Cardiomyocytes have high and fluctuating energy demands and are therefore
prime cellular models to investigate mechanisms responsible for efficient coupling
between energy storage in LDs and utilization in mitochondria (
Mar
´
n-Garc
´
a&
Goldenthal, 2008
). Mitochondrial dysfunction results in prominent lipid accumula-
tion and cardiomyopathy in both mice and humans (
Mar
´
n-Garc
´
a & Goldenthal,
2008
). Conversely, lack of some LD-associated proteins has been associated with
increased mitochondrial
-oxidation of FA in adipose cells (
Beller et al., 2008;
Nishino et al., 2008; Saha, Kojima, Martinez-Botas, Sunehag, & Chan, 2004
).
New studies are revealing an emerging relationship between cardiac LD hydrolysis
and levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha
expression, an important transcription factor for mitochondrial function (
Haemmerle
et al., 2011
). In addition, spatial interaction between these two organelles has
been anecdotally reported in electron microscopic studies of adipocytes, heart
and liver (
Blanchette-Mackie & Scow, 1983; Liu et al., 2007; Shaw, Jones, &
b
