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Am J Physiol Endocrinol Metab (January 24, 2006). doi:10.1152/ajpendo.00401.2005
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Submitted on August 24, 2005
Accepted on January 18, 2006

Effects of the Presence, Absence and Overexpression of Uncoupling Protein-3 on Adiposity and Fuel Metabolism in Congenic Mice

Sheila R Costford1, Shehla N Chaudhry1, Mahmoud Salkhordeh1, and Mary-Ellen Harper1*

1 Department of Biochemistry, Microbiology, Immunology, Univeristy of Ottawa, Ottawa, ON, Canada

* To whom correspondence should be addressed. E-mail: maryellen.harper{at}uottawa.ca.

Uncoupling protein-3 (UCP3) is a poorly understood mitochondrial inner membrane protein expressed predominantly in skeletal muscle. The aim of this study was to examine the effects of the absence or constitutive physiological overexpression of UCP3 on whole body energy metabolism, glucose tolerance and muscle triglyceride content. Congenic male UCP3 -/-, wildtype, and UCP3tg overexpressor mice were fed a 10% fat diet for 4 or 8 months following weaning. UCP3tg mice had lower body weights and were less metabolically efficient than wildtype or UCP3 -/- mice, but were not hyperphagic. UCP3tg mice had smaller epididymal white adipose tissue and brown adipose tissue (BAT) depots, however there were no differences in muscle weights. Glucose and insulin tolerance tests revealed that both UCP3tg and UCP3 -/- mice were protected from development of impaired glucose tolerance and were more sensitive to insulin. 2-deoxy-D-[1-3H]-glucose tracer studies showed increased uptake of glucose into BAT and increased storage of liver glycogen in UCP3 -/- mice. Assessments of intramuscular triglyceride (IMTG) revealed decreases in quadriceps of UCP3tg mice compared to wildtype and UCP3 -/- mice. When challenged with a 45% fat diet, UCP3 -/- mice showed increased accumulation of IMTG compared to wildtype mice, which in turn had greater IMTG than UCP3tg mice. Results are consistent with a role for UCP3 in preventing accumulation of triglyceride in both adipose tissue and muscle.




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