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Publication
Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling
Impairs Myocardial Energetics in Obesity
Authors
Sihem Boudina, Sandra Sena, Brian T O'Neill, Prakash Tathireddy, Martin E Young,
and E. Dale Abel
Submitted By
E. Dale Abel on 11/9/2005
Status
Published
Journal
Circulation
Year
2005
Date Published
10/25/2005
Volume : Pages
112 : 2686 - 2695
PubMed Reference
16246967
Abstract
Obesity is a risk factor for cardiovascular disease and is strongly associated
with
insulin resistance and type 2 diabetes. Recent studies in obese humans and
animals demonstrated increased myocardial oxygen consumption (MVO2) and reduced
cardiac efficiency (CE). However, the underlying mechanisms remain unclear. The
present study was performed to determine if mitochondrial dysfunction and
uncoupling are responsible for reduced cardiac performance and efficiency in
ob/ob mice. Methods and Results?Cardiac function, MVO2, mitochondrial
respiration and ATP synthesis were measured in 9 week-old ob/ob and control
mouse hearts. Contractile function and MVO2 in glucose-perfused ob/ob hearts
were similar to
controls under basal conditions but were reduced under high workload. Perfusion
of ob/ob hearts with glucose and palmitate increased MVO2 and reduced CE by 23%
under basal conditions, and CE remained impaired at high workload. In
glucose-perfused ob/ob hearts, mitochondrial state 3 respirations were reduced
but ATP/O ratios were unchanged. In contrast, state 3 respiration rates were
similar in ob/ob and control mitochondria from hearts perfused with palmitate
and glucose, but ATP synthesis rates and ATP/O ratios were significantly reduced
in ob/ob, suggesting
increased mitochondrial uncoupling. Pyruvate dehydrogenase activity and protein
levels of complexes I, III and V, were reduced in obese mice. Conclusions?These
data indicate that reduced mitochondrial oxidative capacity may contribute to
cardiac dysfunction in ob/ob mice. Moreover, fatty acid (FA) but not
glucose-induced mitochondrial uncoupling reduces CE in obese mice by limiting
ATP production and increasing MVO2. Key Words: Obesity, metabolism,
mitochondria.
Investigators with authorship
Name
Institution
E. Dale Abel
University of Iowa
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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