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United States Department of Agriculture

Agricultural Research Service

Research Project: Linking Foods, Behavior and Metabolism to Promote a Healthy Body Weight

Location: Obesity and Metabolism Research Unit

Title: Muscle UCP3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete beta-oxidation

Authors
item Aguer, Celine -
item Feihn, Oliver -
item Seifert, Erin -
item Bezaire, Veronica -
item Meissen, John -
item Daniels, Amanda -
item Scott, Kyle -
item Renaud, Jean-Marc -
item Padilla, Marta -
item Bickel, David -
item Dysart, Michael -
item Adams, Sean
item Harper, Mary-Ellen -

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 24, 2013
Publication Date: October 1, 2013
Citation: Aguer, C., Feihn, O., Seifert, E.L., Bezaire, V., Meissen, J., Daniels, A., Scott, K., Renaud, J., Padilla, M., Bickel, D., Dysart, M., Adams, S.H., Harper, M. 2013. Muscle UCP3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete beta-oxidation. Journal of Federation of American Societies for Experimental Biology. 27:4213-4225..

Interpretive Summary: Exercise substantially improves metabolic health, making the elicited mechanisms important targets for novel therapeutic strategies. Uncoupling protein 3 (UCP3) is a mitochondrial inner membrane protein highly selectively expressed in skeletal muscle. Here we report that only moderate UCP3 over expression (roughly 3-fold) in muscle of mice (UCP3 Tg) acts in many ways as an exercise mimetic. UCP3 over expression increased spontaneous activity and energy expenditure, and decreased oxidative stress, similar to exercise training in wild-type mice (WT). Complete fatty acid oxidation was higher in UCP3 Tg and trained WT, and was lower in untrained WT mice. Moreover, increases in circulating short-chain acylcarnitines in response to acute exercise in untrained WT were absent with training or in UCP3 Tg mice. UCP3 over expression had the same effect as training in decreasing long-chain acylcarnitines. Overall, results demonstrate that UCP3 is an important target to induce at least some of the beneficial effects of exercise training.

Technical Abstract: Exercise substantially improves metabolic health, making the elicited mechanisms important targets for novel therapeutic strategies. Uncoupling protein 3 (UCP3) is a mitochondrial inner membrane protein highly selectively expressed in skeletal muscle. Here we report that only moderate UCP3 overexpression (roughly 3- fold) in muscle of mice (UCP3 Tg) acts in many ways as an exercise mimetic. UCP3 overexpression increased spontaneous activity (~40%) and energy expenditure (~5-10%), and decreased oxidative stress (~15-20%), similar to exercise training in wild-type mice (WT). The increased in complete fatty acid oxidation and energy expenditure in response to endurance training was higher in UCP3 Tg than WT (~30% for WT and ~70% for UCP3 Tg and ~8% and 15%, respectively) showing a synergistic effect of UCP3 and endurance training on these two parameters. Moreover, increases in circulating short-chain acylcarnitines in response to acute exercise in untrained WT were absent with training or in UCP3 Tg mice. UCP3 overexpression had the same effect as training in decreasing long-chain acylcarnitines. Outcomes coincided with a reduction in muscle CrAT activity that catalyzes the formation of acylcarnitines. Overall, results are consistent with the conclusions that circulating acylcarnitines could be used as a marker of incomplete muscle FAO and that UCP3 is a potential target for the treatment of prevalent metabolic diseases such as T2DM.

Last Modified: 7/31/2014
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