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
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,

Investigators with authorship
E. Dale AbelUniversity of Iowa