Downregulation of skeletal muscle UCP-3 gene expression during refeeding is prevented by cold exposure

We wished to gain insights into the role of skeletal muscle uncoupling prot ein-3 (UCP-3) in the elevated efficiency of fat recovery during refeeding a fter starvation. Previous observations have revealed that muscle UCP-3 expr ession is downregulated in rats during refeeding at 22 degrees C. Therefore , we investigated whether this also occurs during refeeding at thermoneutra lity (29 C) or in the cold (6 C), since at these environmental temperatures the refed animals also show diminished thermogenesis and a higher rate of fat deposition than controls. The UCP-3 mRNA level in the skeletal muscles studied (soleus, gastrocnemius and tibialis anterior) was significantly low er in the refed group than in controls at thermoneutrality, but there were no such differences between these two groups in the cold. This effect of co ld, namely abolishing refeeding-induced downregulation of skeletal muscle U CP, is specific to UCP-3 since the gene expression of skeletal muscle UCP-2 remained significantly lower in the refed than in the controls both at the rmoneutrality and in the cold. These findings during refeeding in the cold therefore dissociate UCP-3 gene regulation from the adaptive reduction in t hermogenesis that accelerates fat deposition during weight recovery. They a lso reveal differential responses of UCP-3 and UCP-2, whose significance is discussed in the light of our previously proposed hypothesis, which center s upon a role for these UCP homologues in the regulation of lipids as a fue l substrate.