D Ricquier

..Interestingly, the T1 gene encoding the heart-skeletal muscle ADP/ATP carrier has recently been shown to be on the same chromosome (Li et al. Biol Chem 264:13998, 1989)...

..Other aims will be to investigate the possible roles of UCP2 and UCP3 in response to oxidative stress, lipid peroxidation, inflammatory processes, fever and regulation of temperature in certain specific parts of the body...

..Their biological importance should be studied. They also represent new putative targets for drugs against metabolic diseases such as obesity...

..Recent genetic, biochemical and physiological studies suggest that these novel UCP2 contribute to resting metabolic rate, fat oxidation and may represent new targets for anti-obesity compounds...

..This response was obtained with a larger DNA fragment (bp -2489 to -2398) constituting a complex RA response domain...

..Although the biochemical activities and physiological roles of the novel UCPs are not well understood, these recent data stimulate research on mitochondrial carriers, mitochondrial bioenergetics, and energy expenditure...

..Activity and expression of the three UCP's are stimulated by several neuromediators and hormones such as noradrenaline, tri-iodothyronine and leptin...

..However, very recent data suggest an important role for the UCPs in the control of production of free radicals by mitochondria, and in response to oxidants...

..In other respects, analysis of molecular mechanisms controlling respiration uncoupling may contribute to new strategies of treatment of metabolic disorders such as obesity...

..Analysis of several genomic clones encompassing UCP2 and/or UCP3 genes demonstrated that the 2 genes are adjacent, the human UCP2 gene being located 7 kb downstream of the UCP3 gene...

..Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli...

..However, we postulate that the C/A substitution, in human, may contribute to a minor defect in the regulation of hUCP1 transcription and that would explain fat gain over time...

..This further level of regulation of the ucp2 gene provides a mechanism by which expression can be strongly and rapidly induced under stress conditions...

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..However, several physiological studies question such a role. Importantly, UCP2 and UCP3 seem to be able to control the activity of mitochondria in response to oxidants...

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..8 kb mRNA in human brown adipose tissue obtained from six patients with phaeochromocytoma and from one patient with a hibernoma. This molecular probe is a new, sensitive and reliable tool with which to study human brown adipocytes...

..This lively awaited information may be the basis for potential pharmacological targeting of the UCPs in future...

..This topological study together with previous data on the UCP provides an experimental basis for the predicted structure of the UCP and for other homologous carrier proteins...

..It was concluded that the drug could affect the brown adipose cells through a beta 3-pathway. It could clearly modulate the expression of UCP in brown adipocytes differentiated in vitro, but was not able by itself to turn on the gene...

..6- and 2.6-fold in cold-acclimated and glucagon-treated ducklings developing muscle non-shivering thermogenesis respectively. The present data support the implication of avUCP in avian energy expenditure...

..The bovine might represent a good model to understand the transition from brown to white fat in the human...

..3-kb allele was found in individuals who gained more body fat over time...

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..Moreover, UCP3 mRNA expression in muscle was decreased...

..Evidence for homology between Uncoupling Protein and Neurospora crassa ADP/ATP carrier at the gene level was also noticed...

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..001 ), which was absent in the presence of a quencher of reactive oxygen species (ROS). Our results indicate a role for Ucp2 in the limitation of ROS and macrophage-mediated immunity...

..We found a significant sequence homology between the uncoupling protein and the ADP/ATP carrier and propose that the nucleotide binding site of the uncoupling protein is localized at the C-terminal end...

..The results suggest a possible role for UCP2 and UCP3 in the increase of energy expenditure associated with cytokine treatment...

..Taken together, these data indicate that PPARgamma activates the UCP2 gene indirectly by altering the activity or expression of other transcription factors that bind to the UCP2 promoter...

..It is concluded that seasonal improvements of in vivo and in vitro thermogenesis are very similar in these species, although the physiological basis for this improvement is different in Clethrionomys and Apodemus...

..05) and apoptosis (P<0.05), along with a decrease in collagen content (P<0.05), suggesting a potentially more vulnerable phenotype. CONCLUSION: These results suggest a protective role for UCP2 against atherosclerosis...

..beta 3-AR may thus be involved in the control of lipid metabolism, possibly from fat assimilation in the digestive tract, to triglyceride storage and mobilization in adipose tissues...