Brown Fat UCP1 Is Specifically Expressed in Uterine Longitudinal Smooth Muscle Cells

Abstract

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...

Uncoupling Protein 2, but Not Uncoupling Protein 1, Is Expressed in the Female Mouse Reproductive Tract

“…A recent publication has presented evidence for Ucp1 expression in the longitudinal smooth muscle of uterus (1). This observation challenges the prevailing view that Ucp1 is expressed exclusively in brown adipocytes.…”

“…Uncoupling proteins (UCPs) 1 belong to the family of transporters present in the inner membrane of mitochondria. UCP1, the first member identified, is uniquely expressed in brown adipocytes where it stimulates heat production by uncoupling oxidative phosphorylation (2)(3)(4).…”

Brown fat and nonshivering thermogenesis in the gray mouse lemur (Microcebus murinus)

“…We suggest interspecific comparisons be made between mouse lemur species and the sibling fat-tailed dwarf lemur Cheirogaleus medius, which is a true hibernator. Finally, UCP1 has recently been found in mouse longitudinal smooth muscle cells of sexual and gastrointestinal tracts (34), suggesting that UCP1 may be involved in the relaxation of smooth muscle layers. Gray mouse lemurs appear as a convenient model of primate for studies on BAT and extra-BAT UCPs.…”

“…For immunochemical analyses, as already described (33,34), one male was exposed to cold (7°C) twice for 12 h. A control male was maintained at 23-25°C. Both were killed by decapitation after an overdose of CO2.…”

La protéine découplante du tissu adipeux brun (UCP1) : la fin des dogmes

“…Or, comme il a été dit précédemment, les souris UCP1 -/-, et particulièrement les femelles, étaient extrêmement sensibles au froid. Les autres souris avaient des problèmes de reproduction difficilement explicables par le seul rôle dans la thermogenèse attribué à l'UCP1, ce qui nous a poussé à rechercher l'expression d'UCP1 dans d'autres tissus [14]. C'est ainsi que l'expression d'UCP1 (protéine et ARNm) a pu être mise en évidence dans l'utérus chez la souris et la ratte.…”