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Biomedical subjects

M Combes-George

Publications and source records attributed to M Combes-George.

10 recordsLinked to original sources

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↗

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↗

An immunological study of the uncoupling protein of brown adipose tissue mitochondria.

1. Ewes were injected with purified 32,000-Mr uncoupling protein from mitochondria of brown adipose tissue of cold-adapted rats in order to raise antibodies. 2. The existence of antibodies in the plasma of ewes and the cross-reactivity of plasmas were demonstrated and studied by 125I-labelled antigen-antibody reaction, double immunodiffusion, the inhibition of GDP binding to the 32,000 Mr protein and by immunohistochemistry. 3. The antibodies raised against the homogeneous protein yielded a single immunoprecipitation band with detergent-solubilized mitochondrial membranes of brown adipose tissue from rat, hamster, guinea-pig, rabbit and with the purified uncoupling protein of these animals. No immunoprecipitation was obtained with the protein purified from brown adipose tissue of term lamb foetus. 4. The GDP-binding activity of the uncoupling protein (isolated or in solubilized membranes) was largely inhibited by the antiserum. 5. The anti-(rat uncoupling protein) could not cross-react with solubilized membranes from liver or muscle, nor with the purified beef heart or rat liver ADP/ATP translocator.

Adipose Tissue, Brown↗

Localization of serotonin and dopamine in the brown adipose tissue of the rat and their variations during cold exposure.

The variations of several biogenic amines in brown adipose tissue (BAT) during cold exposure were studied and their localization investigated with histological methods. The study of serotonin and its metabolite 5-HIAA suggests that BAT serotonin is mobilized during acute and chronic cold exposure. This amine was found to be principally stored, together with histamine, in mast cells. The mast cell number in BAT was doubled during cold adaptation, as was the histamine content of the tissue. Using radio-enzymatic assay and high pressure liquid chromatography, only small amounts of dopamine were found in BAT. Since no specific dopamine-storing structure was detected (for example SIF cells), this low amount of dopamine is probably the precursor pool for noradrenaline synthesis and is most likely stored in the noradrenergic innervation of the tissue. BAT is known to be sensitive to both exogenous serotonin and exogenous dopamine; according to our results serotonin could play a role in BAT regulation while the role of dopamine remains hypothetical.

Acclimatization↗

Development and activation of brown fat in rats with pheochromocytoma PC 12 tumors.

To study the neurohormonal determinism of cellular growth and differentiation and mitochondrial development in brown adipose tissue (BAT), this organ was analyzed in rats bearing uncloned or cloned (PC 12) pheochromocytoma; comparison was made with cold adaptation. Both uncloned and PC 12 tumors induced an enlargement of tissue weight and DNA total content, although smaller than during cold adaptation. The following striking modifications were observed in rats bearing PC 12 tumors: strong vasodilation, increase in protein and phospholipid percentage, alteration of the fatty acid composition of phospholipids, increase in mitochondrial protein, large increase of the GDP binding to isolated mitochondria, and marked rise in specific amount of 32,000-dalton uncoupling protein (ascertained using immunological approach). It is concluded that secretions of PC 12 tumors can induce the same alterations in BAT as does the sympathetic system during cold adaptation of animals. An important contribution of norepinephrine to these effects is evidenced, but a specific function of other trophic factors secreted by PC 12 cells and by sympathetic nerves can be postulated.

Acclimatization↗