Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein thermogenin: Effects of hypothyroidism and norepinephrine

Rehnmark, Stefan; Kopecký, Jan; Jacobsson, Anders; Nechad, M.; Herron, David K.; Nelson, Bruce R.; Obregón, Marı́a-Jesús; Nedergaard, Jan; Cannon, Barbara

doi:10.1016/0014-4827(89)90280-2

Cited by 79 publications

(33 citation statements)

References 29 publications

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“…Thus, in preconfluent cultured cells, norepineph~ne stimulation led to a decrease in the CIEBPa mRNA level, whereas in the confluent cells, the CIEBPa mRNA level was increased. Such a switch in responsiveness between preconfluent and confluent brown fat cells has earlier been observed for other phenomena: norepinephrine can promote cell proliferation in the preconfluent cultures [18,34] and cell differentiation (including gene expression) in the confluent cultures [l&21, 28,35], As the stem cells in the tissue are induced to proliferate by the exposure of the animals to cold, these cells in vivo are probably initially and transiently in the same phase as the preconfluent cells in vitro, and as the cells in vivo are exposed to an endogenous stimulation with norepinephrine, released from the sympathetic nervous system, they respond in the same way as the cells in vitro: with a decreased expression of the ClEBPol gene. Conversely, when the cells in vivo are in a dormant phase (as in the animals at ZS'C), they respond to a single norepinephrine injection (which is apparently not sufficient to induce cell proliferation) with a tendency to an increased C/EBPcl gene expression (Fig.…”

Section: Ciebpa and Cell Proliferationmentioning

confidence: 59%

Differential adrenergic regulation of C/EBPα and C/EBPβ in brown adipose tissue

et al. 1993

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"The Wenner-wren institute, The Arrhenius ~ohoratorie~ F3, Stockholm university, S-106 91 Stockholm, Sweden and bKarolinska Institute* Center for biotechnology, NOVUM, S-14f 57 ~~ddinge* Sweden Received 11 January 1993We investigated the regulation of the expression of two members of the C/EBP family of transcriptional activators, CIEBPa and CIEBPB, in brown adipose tissue in mice. Less than one hour of cold exposure led to dramatic changes in the expression of both genes, ClEBPa steady-state mRNA and protein levels were drastically and rapidly reduced whereas C/EBP/l mRNA and protein levels were induced severalfold. Also norepinephrine injection affected the expression of the transcription factors. Preconfluent cells in brown fat primary cultures responded to norepinephrine with a decrease in CIEBPa and an increase in CIEBPB mRNA; in confluent cells the expression of both factors was increased. Thus, C/EBPcl and CIEBPB gene expression is under adrenergic control both in vivo and in vitro but the type of response is directed by the degree of differentiation of the cells.

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Section: Ciebpa and Cell Proliferationmentioning

confidence: 59%

Differential adrenergic regulation of C/EBPα and C/EBPβ in brown adipose tissue

et al. 1993

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“…The interscapular BAT and epididymal WAT of 4-to 6-weekold male 129 Sv/ev mice were excised and their precursor cells isolated according to Rehnmark et al, 20 and cultured using a modification of the brown adipocyte differentiation medium described by Champigny et al 19 This medium consisted in DMEM/F12 medium containing fetal bovine serum 10%, ascorbic acid 200 mM, insulin 20 nM, T3 0.2 nM, penicillin 100 U ml À1 and streptomycin 50 mg ml À1 . In addition, from the second day on, 1 mM of the b 3 -adrenoceptor agonist, CL 316243 was added to the culture medium.…”

Section: Adipocyte Primary Culturementioning

confidence: 99%

Differentiation and characterization in primary culture of white adipose tissue brown adipocyte-like cells

Lehr¹,

Canola²,

Léger

et al. 2009

Int J Obes

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Background: Rodent brown adipose tissue (BAT) is considered the main effector of adaptative thermogenesis as it contains a unique mitochondrial uncoupling protein, termed as uncoupling protein-1 (UCP1). The emergence of ectopic brown adipocytes in the white adipose tissue (WAT), called recruitment, might play an important role in the prevention of obesity. The recruitment phenomenon has until now been investigated mostly in vivo. Objectives: This study is an attempt to mimic in vitro the recruitment phenomenon. It consisted in culturing the stroma vascular fractions of mouse BAT and WAT in a brown adipocyte differentiation medium. The multilocular cells obtained, referred to as BAT B and WAT B adipocytes, respectively, were compared. Results: The BAT B and WAT B adipocytes were morphologically different. The expressions of UCP1, peroxisome proliferatoractivated receptor-g coactivator-1a (PGC-1a), leptin and resistin mRNAs were low in WAT B adipocytes as compared with those in BAT B adipocytes. The expressions of UCP1 and PGC-1a proteins were, however, much higher in WAT B adipocytes, amounting 51% and 36% of those in BAT B adipocytes. The patterns of expression of UCP1, PGC-1a and leptin in the BAT B and in WAT B adipocytes were different with a higher relative expression of PGC-1a in the latter. Rosiglitazone increased UCP1 mRNA expression 4.5-fold in the BAT B and significantly more, 7.9-fold, in the WAT B adipocytes. Retinoic acid and triiodothyronine increased UCP1 mRNA expression in the BAT B adipocytes 1.6-and 2-fold, respectively but, surprisingly, slightly decreased UCP1 mRNA expression in the WAT B adipocytes. Conclusions: The study suggests that the nature and possibly the origin of WAT brown adipocytes is different from that of BAT brown adipocytes. It proposes an in vitro approach that could prove very useful to better characterize the WAT brown adipocyte-like cells.

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“…20,21 Precursor cells were suspended in culture medium (cells from 1 mouse in 0.5 ml), pooled and inoculated in 6-well multidish plates (0.2 ml of pooled ®nal cell suspension per well containing 1.8 ml of culture medium). The culture medium consisted of DMEM supplemented with 10% NCS, 4 nM insulin, 10 mM HEPES, 50 units of penicillin/ml, 50 mg of streptomycin/ml and 25 mg of sodium ascorbate/ml.…”

Section: Primary Cell Culturementioning

confidence: 99%

Stimulation of uncoupling protein 1 expression in brown adipocytes by naturally occurring carotenoids

et al. 1999

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OBJECTIVE: To assess the effect of naturally occurring carotenoids on brown adipocyte proliferation and differentiation. The rationale behind is that certain carotenoids have provitamin A activity in mammals, and that one of the active forms of vitamin A, (retinoic acid) is known to behave as a transcriptional activator of the key gene for brown fat thermogenesis, the one encoding the uncoupling protein thermogenin (UCP1). DESIGN: Con¯uent primary cultures of mice brown adipocytes were treated with various concentrations of carotenoids. Cell morphology, total culture protein content, the DNA synthesis rate, and the levels of UCP1, retinoic acid receptor a (RARa) and retinoid X receptor a (RXRa) were analysed. RESULTS: Treatment with b-carotene, a-carotene and lutein promoted UCP1 expression in a dose-dependent manner, with an effectiveness that was related to their potency as vitamin A precursors. Cell morphology, total culture protein content at con¯uence and DNA synthesis rate were unaffected after carotenoid treatment up to 10 mM. CONCLUSION: The results indicate that carotenoids can positively affect the expression of UCP1 without altering brown adipocyte proliferation.

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Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein thermogenin: Effects of hypothyroidism and norepinephrine

Cited by 79 publications

References 29 publications

Differential adrenergic regulation of C/EBPα and C/EBPβ in brown adipose tissue

Differential adrenergic regulation of C/EBPα and C/EBPβ in brown adipose tissue

Differentiation and characterization in primary culture of white adipose tissue brown adipocyte-like cells

Stimulation of uncoupling protein 1 expression in brown adipocytes by naturally occurring carotenoids

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