Until now, uncoupling protein 1 (UCP1) was considered as unique to brown adipocytes. It supports a highly regulated uncoupling of oxidative phosphorylation that is associated with diet as well as with non-shivering thermogenesis. Here we report that UCP1 is not specific to brown adipocytes and can be expressed in longitudinal smooth muscle layers. In the uterus, this conclusion was drawn from different convergent data. A specific antibody against mouse UCP1 revealed, in mitochondrial fractions, a protein with the same molecular weight as brown fat UCP1. Sensitive and specific reverse transcriptase-polymerase chain reaction detected a mRNA whose sequence was totally homologous to that of brown fat UCP1 mRNA. Antibody against UCP1 as well as a UCP1 antisense probe specifically stained uterine longitudinal smooth muscles. UCP1 was also expressed in longitudinal smooth muscle of digestive and male reproductive tracts but was never expressed in other types of smooth muscle, including those of arterial vessels. In uterine tract, UCP1 content was increased after cold exposure or ␤-adrenergic agonist treatment. It was also up-regulated during the postovulatory period after sexual cycle synchronization. Its content transiently increased during gestation and decreased markedly after birth. These regulations strongly argue about a role for UCP1 in thermogenesis as well as in relaxation of longitudinal smooth muscle layers.The primary function of mitochondria is to supply the cell with energy as ATP. They are also involved in heat production and have other functions that are not directly related to energy transduction, such as redox state control and Ca 2ϩ homeostasis. (1, 2). In all the functions, membrane potential and permeability play key roles. In specialized thermogenic cells, such as the brown adipocyte, increased proton conductance across the mitochondrial inner membrane was first postulated by Nicholls and Locke (3). The protein supporting this activity was later purified, named uncoupling protein (UCP), 1 and cloned. This protein belongs to the mitochondrial anion carrier family. Its insertion into the mitochondrial inner membrane allows dissipation of the proton electrochemical gradient across this membrane with associated heat production and decreased ATP synthesis. Its ectopic expression in any eukaryotic cell is sufficient to reproduce similar uncoupled mitochondrial phenotypes (4, 5). Until now, its expression was only detected in mitochondria from brown adipocytes. The recent cloning and expression studies of other UCPs, such as UCP2 and UCP3, suggest that similar mechanisms may exist in numerous cells. New perspectives with regard to UCPs and particularly UCP1 are now being revealed with the discoveries that UCPs are modulators of mitochondrial reactive oxygen species generation and that coenzyme Q is an obligatory partner for their uncoupling activity (6, 7).The function of the different UCPs in the maintenance of body temperature has been debated (8). Until now, only UCP1 has been clearly linked to thermo...

In mammals, two types of adipose tissue are present, brown and white. They develop sequentially, as brown fat occurs during late gestation whereas white fat grows mainly after birth. However, both tissues have been shown to have great plasticity. Thus an apparent transformation of brown fat into white fat takes place during post-natal development. This observation raises questions about a possible conversion of brown into white adipocytes during development, although indirect data argue against this hypothesis. To investigate such questions in vivo, we generated two types of transgenic line. The first carried a transgene expressing Cre recombinase specifically in brown adipocytes under the control of the rat UCP1 promoter. The second corresponded to an inactive lacZ gene under the control of the human cytomegalovirus promoter. This dormant gene is inducible by Cre because it contains a Stop sequence between two loxP sequences, separating the promoter from the coding sequence. Adipose tissues of progeny derived by crossing independent lines established from both constructs were investigated. LacZ mRNA corresponding to the activated reporter gene was easily detected in brown fat and not typically in white fat, even by reverse transcriptase PCR experiments. These data represent the first direct experimental proof that, during normal development, most white adipocytes do not derive from brown adipocytes.

To investigate relationships between the uncoupling protein (UCP) family and oxidative metabolism in fat pads, we measured the cytochrome oxidase activity, used as an index of oxidative capacity, and the mRNA content encoding UCP1, UCP2 and UCP3. Most oxidative potential was found in the stromal-vascular fraction (SVF) of brown fat and in mature adipocytes of white fat (inguinal and periovarian). Considering the whole fat pads, the oxidative potential observed in mature white adipocytes fraction was not negligible compared with that of brown adipocytes fraction. UCP1 and UCP3 were expressed exclusively in mature brown adipocytes. Whatever the deposit, UCP2 mRNA was mainly localized in the SVF. These results indicate that, in fat, high oxidative potential is not necessarily linked to high UCPs transcripts content and point out the oxidative capacity of SVF from brown fat.z 1999 Federation of European Biochemical Societies.