PubMed Health⌕ Search

Biomedical subjects

F Bouillaud

Publications and source records attributed to F Bouillaud.

67 records · Page 4Linked to original sources
PubMed1988

Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe.

1. Studies on human brown adipose tissue require specific molecular probes. A human genomic library has been screened with a complementary DNA corresponding to the uncoupling protein (UCP) of rat brown adipose tissue mitochondria. 2. Two recombinant phages were isolated, carrying genomic sequences of human UCP. From them we have subcloned a 0.5 kilobase fragment. This fragment, H-Ucp-0.5, contained two intronic regions and two exonic regions. Exonic regions encoded a sequence of 84 amino acids which exhibited a strong homology with central domain at rat UCP. The organization of H-Ucp-0.5 was confirmed by SI mapping analysis. 3. A Southern analysis suggested that the gene is single type in the human, as it is in rodents. 4. In Northern analysis experiments, H-Ucp-0.5 detected a specific 1.8 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.

Adipose Tissue, Brown↗
PubMed1986

Expression of uncoupling protein mRNA in thermogenic or weakly thermogenic brown adipose tissue. Evidence for a rapid beta-adrenoreceptor-mediated and transcriptionally regulated step during activation of thermogenesis.

A cloned cDNA sequence for the unique mitochondrial uncoupling protein of rat brown adipose tissue has been used to assay the corresponding mRNA in several situations. When thermogenesis in brown adipose tissue is stimulated (exposure of adult rats to the cold, birth) a rapid and prolonged increase in the level of uncoupling protein mRNA is observed. Such an increase can be mimicked by injection of animals with a new beta-adrenoreceptor agonist BRL 26830A. Conversely it is known that mice and rats with genetic or surgical obesity have a weakly thermogenic brown adipose tissue with a reduced norepinephrine turnover. A reduced level of uncoupling protein mRNA was measured in obese fa/fa rats 10 days or 10 weeks old and in obese rats with a lesion of the ventromedial hypothalamic area but not in obese ob/ob mice. Moreover, exposure of obese animals to cold or dosing with BRL 26830A strikingly increased the level of uncoupling protein mRNA. Measurement of the relative concentration of nascent Ucp transcripts in nuclei isolated from brown adipose tissue indicates that Ucp gene is acutely (within 15 min) regulated at the level of transcription and is controlled via activation of beta-adrenoreceptors of plasma membrane. Ucp gene transcription is decreased in obese fa/fa rats but can be fully and rapidly turned on after injection of BRL 26830A.

Adipose Tissue, Brown↗
PubMed1986

Complete cDNA-derived amino acid sequence of rat brown fat uncoupling protein.

Cloned cDNAs corresponding to the mitochondrial uncoupling protein of rat brown adipose tissue have been sequenced and the complete amino acid sequence of this unique membranous component is given. The N-terminal sequence of this protein is almost identical to the 14-residue N-terminal sequence previously determined by others for the hamster uncoupling protein. The uncoupling protein has no N-terminal signal extension. 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.

Adipose Tissue, Brown↗
PubMed1985

Increase of uncoupling protein and its mRNA in brown adipose tissue of rats fed on 'cafeteria diet'.

The effect of 'cafeteria diet' on mitochondrial uncoupling protein in brown adipose tissue of rats was examined. 'Cafeteria diet' induced an increase of the 32 kDa uncoupling protein in electrophoresed proteins of brown-fat mitochondria. Use of a cDNA probe corresponding to uncoupling-protein mRNA indicated that this mRNA was increased in rats fed on the 'cafeteria diet'. Nevertheless, this effect was weak compared with that observed in rats adapted to cold.

Adipose Tissue, Brown↗
PubMed1985

Factors controlling brown adipose tissue development.

Brown adipose tissue (BAT) is a site of non-shivering thermogenesis in mammals. Thermogenesis in brown adipocytes is related to the presence of a specific mitochondrial component called "uncoupling protein". When animals are chronically exposed to cold, their BAT is enlarged and exhibits several changes such as cellular differentiation, hyperplasia, mitochondriogenesis and marked synthesis of uncoupling protein. The hormonal and neural factors controlling this adaptive response have been studied. It is concluded that sympathetic innervation of BAT and released noradrenaline play an essential role in the development of BAT.

Adaptation, Physiological↗
PubMed1985

Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein.

The uncoupling protein (UCP) of mammalian brown fat is a specialized and unique component responsible for energy dissipation as heat. Translation and immunoprecipitation from sucrose-fractionated mRNA indicated that the mRNA of UCP sedimented at 14-16 S. A recombinant cDNA library prepared from mRNA of thermoactive brown fat enriched for UCP mRNA has been constructed and cloned in Escherichia coli. Recombinant plasmids were screened by differential colony hybridization to a cDNA probe complementary to poly(A)+ RNA isolated from thermogenic or from weakly thermogenic brown fat. Several differentially hybridizing plasmids were shown to contain UCP cDNA sequences by their ability to select a mRNA coding for an in vitro translation product that was immunoprecipitable with antibodies against UCP. Blot hybridization of brown fat mRNA to a 32P-labeled UCP cDNA probe revealed two major species of mRNA (15S and 18S). As compared to non-thermogenic tissue, a strikingly increased hybridization to the probe was observed with brown fat mRNA from thermoactive tissue. Moreover, hybridization was observed with RNA of brown adipose tissue from rat, hamster, or mouse but not with RNA from rat or mouse liver.

Adipose Tissue, Brown↗
PubMed1984

Rapid increase of mitochondrial uncoupling protein and its mRNA in stimulated brown adipose tissue. Use of a cDNA probe.

The increase in mitochondrial uncoupling protein in brown adipose tissue during acute stimulation by exposure of animals to cold was examined. Uncoupling protein level increased during the first hours of tissue stimulation. Use of a cDNA probe shows that synthesis of uncoupling protein mRNA was quickly stimulated. Animals treated with propranolol exhibited neither increase in uncoupling protein mRNA nor increase in the protein itself.

Adipose Tissue, Brown↗
PubMed1984

Increased level of mRNA for the uncoupling protein in brown adipose tissue of rats during thermogenesis induced by cold exposure or norepinephrine infusion.

We have studied by in vitro translation the mRNA population from rat brown fat in two situations where the thermogenic activity of the tissue is stimulated. Both cold exposure of rats and the presence of pheochromocytoma result in marked alterations among the polypeptides synthesized. Notably, in these two situations there was an increased labeling of polypeptides of the size of the heat-shock proteins and an increased labeling of the 32,000-dalton uncoupling protein of brown fat mitochondria, which is responsible for energy dissipation as heat. Stimulation of the thermogenic activity of brown fat thus results in a high level of mRNA encoding the uncoupling protein. Chronic delivery of norepinephrine mimicked the increase of mRNA for the uncoupling protein observed in animals exposed to cold or bearing pheochromocytoma. Thus, a neuromediator such as norepinephrine is able to trigger the induction of the mRNA encoding the mitochondrial uncoupling protein and is able to stimulate mitochondriogenesis.

Adipose Tissue, Brown↗
PubMed1984

Noradrenaline controls the concentration of the uncoupling protein in brown adipose tissue.

The importance of noradrenaline in the control of the level of the uncoupling protein responsible for the high thermogenic capacity of brown adipose tissue mitochondria was examined. It was observed that chronic infusion of noradrenaline through mini-osmotic pumps increased the mitochondrial concentration of this uncoupling protein to the same extent as chronic exposure to cold.

Adipose Tissue, Brown↗
PubMed1984

Modulation of beta-oxidation and proton conductance pathway of brown adipose tissue in hypo- and hyperinsulinemic states.

The metabolic capacity of interscapular brown adipose tissue of hypoinsulinemic (diabetic) rats is decreased and a reduced beta-oxidative capacity contributes to this metabolic alteration. It was thus of interest to compare, in diabetic and in chronically (8 days) insulin-infused rats, the beta-oxidative capacity and indices of the thermogenic state (GDP-binding and 32 000 Mr protein) in this tissue. Mitochondrial GDP-binding and 32 000 Mr protein were both decreased in diabetic rats compared to appropriate controls and markedly increased as was also the beta-oxidative capacity in hyperinsulinemic rats.

Adipose Tissue↗
PubMed1983

The possible proton translocating activity of the mitochondrial uncoupling protein of brown adipose tissue. Reconstitution studies in liposomes.

Loose coupling of thermogenic mitochondria of brown adipose tissue is related to a high proton (or hydroxyl) conductance of the inner membrane and to the presence of a unique 32 kDa uncoupling protein. Reconstitution experiments of the purified protein in liposomes are reported which suggest that this component could form proton channels in the membrane.

Adenosine Monophosphate↗
PubMed1983

Molecular approach to thermogenesis in brown adipose tissue. Cell-free translation of mRNA and characterization of the mitochondrial uncoupling protein.

In order to develop a molecular approach of the thermogenesis mechanism in brown adipose tissue, cell-free translation was performed with mRNA obtained from control or thermoactive brown adipose tissue. Alterations were observed on analysis of the newly synthesized proteins and in particular at the 32,000 dalton level. Experiments using antibodies against the purified characteristic 32,000-dalton uncoupling protein of brown fat mitochondria were carried out. They indicated that the uncoupling protein was synthesized in the reticulocyte lysate with the same apparent molecular weight as the mature form. It is suggested that the development of the thermogenic capacity of brown fat cells is accompanied by an increase in specific mRNA coding for the uncoupling mitochondrial protein and that such a system could be an interesting one for study of mitochondrial membrane biogenesis.

Adipose Tissue, Brown↗