Developmental and tissue-specific involvement of peroxisome proliferator-activated receptor-alpha in the control of mouse uncoupling protein-3 gene expression. Endocrinology 2006;147:4695–4704

Uncoupling protein-3 (UCP3) is a member of the mitochon-drial carrier family expressed preferentially in skeletal mus-cle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor- (PPAR) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPAR-null mice both in basal conditions and under the stimulus of starvation. In con-trast,UCP3mRNAisdown-regulated inadultheartboth in fed and fasted PPAR-null mice. This occurs despite the in-creased levels of free fatty acids caused by fasting in PPAR-nullmice. In neonates, PPAR-nullmice show impairedUCP