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CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity.

Cappel DA, Lantier L, Palmisano BT, Wasserman DH, Stafford JM - PLoS ONE (2015)

Bottom Line: There are sexual-dimorphisms in the effects of CETP in humans.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.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-1α).

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

ABSTRACT
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-1α). 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.

No MeSH data available.


Related in: MedlinePlus

CETP expression does not alter weight or adiposity gain on HFD.(A) Body weight over the course of HFD-feeding. (B) Body composition at baseline and 4-weeks post HFD. n = 5–8 mice per group.
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pone.0136915.g001: CETP expression does not alter weight or adiposity gain on HFD.(A) Body weight over the course of HFD-feeding. (B) Body composition at baseline and 4-weeks post HFD. n = 5–8 mice per group.

Mentions: To test the effect of CETP expression on exercise tolerance in female mice, we performed an exercise study in CETP-expressing female mice and their non-transgenic wild-type female littermates. At the beginning of the study, mice were 12 weeks old, had been fed a standard chow diet since weaning, and were lean. There were no differences in initial body weight or body composition between genotypes (Fig 1A and 1B). Mice were subjected to an initial exercise tolerance test consisting of a treadmill run with speed increasing every 3 minutes. The duration, distance, and maximum work rate run by the mice provide an index of exercise capacity. In the initial exercise tolerance test, we saw no difference in exercise capacity between lean, chow-fed CETP mice and their WT littermates. CETP mice ran for an average of 23 ± 2 minutes (535 ± 90 meters) versus 24 ± 2 minutes (586 ±170 meters) for WT mice (Fig 2A, 2B, 2D and 2E). These results show that there is no genotype effect of CETP expression on exercise capacity in the context of a low-fat chow diet.


CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity.

Cappel DA, Lantier L, Palmisano BT, Wasserman DH, Stafford JM - PLoS ONE (2015)

CETP expression does not alter weight or adiposity gain on HFD.(A) Body weight over the course of HFD-feeding. (B) Body composition at baseline and 4-weeks post HFD. n = 5–8 mice per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4551677&req=5

pone.0136915.g001: CETP expression does not alter weight or adiposity gain on HFD.(A) Body weight over the course of HFD-feeding. (B) Body composition at baseline and 4-weeks post HFD. n = 5–8 mice per group.
Mentions: To test the effect of CETP expression on exercise tolerance in female mice, we performed an exercise study in CETP-expressing female mice and their non-transgenic wild-type female littermates. At the beginning of the study, mice were 12 weeks old, had been fed a standard chow diet since weaning, and were lean. There were no differences in initial body weight or body composition between genotypes (Fig 1A and 1B). Mice were subjected to an initial exercise tolerance test consisting of a treadmill run with speed increasing every 3 minutes. The duration, distance, and maximum work rate run by the mice provide an index of exercise capacity. In the initial exercise tolerance test, we saw no difference in exercise capacity between lean, chow-fed CETP mice and their WT littermates. CETP mice ran for an average of 23 ± 2 minutes (535 ± 90 meters) versus 24 ± 2 minutes (586 ±170 meters) for WT mice (Fig 2A, 2B, 2D and 2E). These results show that there is no genotype effect of CETP expression on exercise capacity in the context of a low-fat chow diet.

Bottom Line: There are sexual-dimorphisms in the effects of CETP in humans.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.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-1α).

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

ABSTRACT
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-1α). 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.

No MeSH data available.


Related in: MedlinePlus