Modulation of β‐oxidation and proton conductance pathway of brown adipose tissue in hypo‐ and hyperinsulinemic states

Seydoux, J; Trimble, E.R.; Bouillaud, Frédéric; Assimacopoulos-Jeannet, F.; Bas, Sylvette; Ricquier, Daniel; Giacobino, Jean‐Paul; Girardier, L

doi:10.1016/0014-5793(84)80060-5

Cited by 40 publications

(17 citation statements)

References 21 publications

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“…Such differences in sensitivity are consistent with reduced plasma insulin levels in vivo [12, 311 and insulin sensitivity increased [31] in cold exposure, and indicate greater insulin sensitivity of BAT of the cold-acclimated animal compared with that of the animal at thermoneutrality. Chronic insulin administration has been reported to increase BAT P-oxidative capacity by raising mitochondrial protonophore concentration in vivo [32], but the acute effects of insulin in vitro are less well defined. At supraphysiological concentrations, inhibition of Po?…”

Section: Discussionmentioning

confidence: 99%

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Howland

Bond

1987

Eur J Biochem

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1. The effects of insulin (2 nM and 4 nM) upon oxygen consumption ( VoJ, lipolysis rates and indirectly derived rates of fatty acid utilization, by isolated brown adipocytes from warm-acclimated (W cells) and cold-acclimated (C cells) animals, induced by noradrenaline and glucagon separately and conjointly, are reported.2. Changes in interrelationships (coupling) between the parameters under different treatment regimes were assessed using bivariate regression analyses.3. Administration of glucagon with noradrenaline increased lipolysis/fatty acid utilization coupling without concomitant increase of Vo2 suggesting that glucagon may increase re-esterification through glycogenolytic generation of glycerol 3-phosphate, trapping intracellular fatty acid in excess of the capacity of disposal mechanisms, thus conserving respiratory substrate.4. W cells were unresponsive to glucagon in terms of lipolysis and po2'; C cells responded to glucagon with parallel increases in lipolysis rate and Both cell types responded to noradrenaline alone and conjointly with glucagon; C cells-were more sensitive to these agonists than W cells.5. Lipolysis/ Vo, coupling was reduced in C cells suggesting that in cold acclimation, noradrenaline-induced lipolysis rates are in excess of the capacity of cellular oxidation/re-esterification mechanisms.6. Insulin inhibited noradrenaline and glucagon-induced lipolysis, simultaneously increasing po2, supporting the hypothesis that glucose may be a thermogenic substrate in brown adipase tissue, permitting concurrent thermogenesis and lipogenesis. C cells were more insulin-sensitive than W cells.7. The data indicate that insulin may mediate its effects (additively with noradrenaline) by activation of pyruvate dehydrogenase, generating glycolytic flux and, in the presence of noradrenaline-inhibited lipogenesis, generate additional oxaloacetate, permitting increased P-oxidation.In homeotherms, non-shivering thermogenesis is mediated primarily by brown adipose tissue (BAT) [l]. The principal mechanism of activation is by means of increased sympathetic activity with liberation of noradrenaline from the dense adrenergic terminals with which the tissue is invested, and consequent activation of P-adrenergically mediated lipolysis leading to the liberation of free fatty acids from intracellular triacylglycerols. Subsequent P-oxidation of free fatty acids, associated with increased mitochondrial proton conductance induced by increased free fatty acid concentrations [2], leads to enhanced heat production by dissipation of the mitochondrial proton gradient [3]. A second effect attributed to noradrenaline release in chronic cold exposure is increased synthesis of mitochondrial protonophore [4].While noradrenaline appears to be the prime mediator of BAT thermogenesis [5], there is evidence that non-adrenergic factors such as glucagon [6, 71 may have permissive or

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Section: Discussionmentioning

confidence: 99%

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Howland

Bond

1987

Eur J Biochem

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“…It has been shown before that in diabetic rats or mice, COX activity and mitochondrial protein content were decreased and could be at least partially restored by insulin treatment (13,14). UCP content and proton conductance of rat brown fat are also reduced in a hypoinsulinemic state (39). Geloen and Trahurn (14) could also demonstrate a stimulating effect of insulin on UCP levels, which they showed to be partly, but not entirely mediated by the sympathetic nervous system.…”

Section: Brown Adipocyte Thermogenesis Is Regulated By Several Hormonmentioning

confidence: 94%

Development of Phodopus sungorus brown preadipocytes in primary cell culture: effect of an atypical beta-adrenergic agonist, insulin, and triiodothyronine on differentiation, mitochondrial development, and expression of the uncoupling protein UCP.

Schimrigk

Cassard-Doulcier

Ricquier

1991

The Journal of Cell Biology

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Abstract. A new cellular model for the study of brown adipocyte development and differentiation in vitro is presented . Preadipocytes isolated from brown adipose tissue (BAT) of the djungarian dwarf hamster Phodopus sungorus are able to proliferate and differentiate in vitro into true brown adipocytes able to express the BAT marker protein the uncoupling protein (UCP) . Whereas basal UCP expression is very low, its mRNA levels as well as the UCP detected by immunoblotting are highly increased by 0-adrenergic stimulation. The novel, atypical 0-adrenergic compound D7114 (ICI Pharmaceuticals, Macclesfield, Cheshire, T wo types of adipose tissue with quite different functions are known to exist in mammals : firstly the white adipose tissue whose main function is energy storage, secondly the so-called brown adipose tissue (BAT)', which functions as a heat dissipating organ in small and newborn mammals . This function is due to the uncoupling protein (UCP), uniquely expressed in BAT, which is located in the inner mitochondrial membrane (for review see 24) . UCP functions as a proton translocator and can thus short circuit the coupling between the respiratory chain and ATP production, resulting in elevated respiration rates and dissipation of the energy as heat (28). Contrary to white fat, the BAT is highly innervated and vascularized and brown adipocytes have very high respiratory capacities, i .e., a high content of mitochondria. Brown fat is considered to play an important function in energy balance, by dissipating excess energy intake as heat in certain animal models (38). It is also known that many types of obesity in animals are associated with a defective BAT function (17) . Despite their quite contrary physiological function, it is not yet clear if brown and white adipocytes should be considered as two distinctly different cell types or iftheyjust represent two different differentiation or maturation states of the same cell type. According to our present knowledge, every adipocyte that expresses UCP is England) was found to increase the number of adipocytes as well as UCP mRNA and UCP content of mitochondria, indicating the involvement of an atypical or /33 receptor. Insulin was found to play an important role in brown adipocyte differentiation and mitochondria) development, whereas T3 seemed to be implicated more directly in UCP expression . In a defined, serum-free medium a synergistic stimulatory action of insulin and T3 on UCP expression was found, which seems to involve a pathway different from that of 0-adrenergic UCP stimulation . considered a brown adipocyte, whereas an adipocyte not expressing UCP is not automatically a white adipocyte. In small mammals, like rodents, BAT preserves throughout the animal life its thermogenic ability, i .e., the ability to express UCP. But in larger mammals, like bovine and ovine species, itwas shown that fat depots ofa true brown nature are present at birth, which very rapidly lose their "brown" nature and become typical white depots which will never express UCP anymore...

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“…We found that insulin increased the BAT mass, the metabolic capacity of the tissue, and the concentration of uncoupling protein in BAT mitochondria (Seydoux et al, 1984). Nevertheless, these effects of insulin on BAT were probably both direct (effects on the tissue) and indirect (via activation of the ventromedial hypothalamic nucleus which, in turn, activates the sympathetic fibres innervating BAT) (see discussion by Ricquier and (Jansky, 1973), we examined the role of BAT sympathetic innervation in the trophic response of this tissue during the prolonged exposure of rats to cold.…”

Section: Introductionmentioning

confidence: 67%

Factors controlling brown adipose tissue development

Ricquier¹,

Mory²,

Bouillaud³

et al. 1985

Reprod. Nutr. Dévelop.

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Modulation of β‐oxidation and proton conductance pathway of brown adipose tissue in hypo‐ and hyperinsulinemic states

Cited by 40 publications

References 21 publications

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Development of Phodopus sungorus brown preadipocytes in primary cell culture: effect of an atypical beta-adrenergic agonist, insulin, and triiodothyronine on differentiation, mitochondrial development, and expression of the uncoupling protein UCP.

Factors controlling brown adipose tissue development

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