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Oxymax/Treadmill Max Test Order #7711 2/19/13
Pharmacological approaches to reduce obesity have not resulted in dramatic
reductions in the risk of coronary heart disease (CHD). Exercise, in contrast,
reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer
Protein (CETP) is a lipid transfer protein that shuttles lipids between serum
lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in
humans. Mice naturally lack CETP, but we previously reported that transgenic
expression of CETP increases muscle glycolysis in fasting and protects against
insulin resistance with high-fat diet (HFD) feeding in female but not male mice.
Since glycolysis provides an important energy source for working muscle, we
aimed to define if CETP expression protects against the decline in exercise
capacity associated with obesity. We measured exercise capacity in female mice
that were fed a chow diet and then switched to a HFD. There was no difference in
exercise capacity between lean, chow-fed CETP female mice and their
non-transgenic littermates. Female CETP transgenic mice were relatively
protected against the decline in exercise capacity caused by obesity compared to
WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP
mice showed a nearly two-fold increase in run distance compared to WT. After an
additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout
and muscle mitochondria were isolated. We found that improved exercise capacity
in CETP mice corresponded with increased muscle mitochondrial oxidative
capacity, and increased expression of peroxisome proliferator-activated receptor
gamma coactivator 1-alpha (PGC-1a). These results suggest that CETP can protect
against the obesity-induced impairment in exercise capacity and may be a target
to improve exercise capacity in the context of obesity.
Applicable research areas: Diabetes, Metabolism
day(s) post-natal (d)
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Name / Abbreviation
Experimental Factor: Experimental Group
This animal belongs to the control group for the experiment.
This animal belongs to experimental group that is homozygous for gene manipulations.
Experimental Factor: Treadmill Speed (m/min)
The speed of the treadmill used during an energy expenditure experiment
Experimental Factor (Units)
Treadmill Speed (m/min)
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fat body mass
fat body mass
lean body mass
lean body mass
body water, free
heat (Light Period)
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Mammalian Phenotype (MP) Terms
increased percent water in carcass
more than the normal total amount of water retained in the body measured post mortem [MGI:il]
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Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
) under the MICROMouse Program, grants DK076169.
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