Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1

Tsukiyama-Kohara, Kyoko; Poulin, Francis; Kohara, Michinori; DeMaria, Christine T.; Cheng, Alan; Wu, Zhidan; Gingras, Anne‐Claude; Katsume, Asako; Elchebly, Mounib; Spiegelman, Bruce M.; Harper, Mary‐Ellen; Tremblay, Michel L.; Sonenberg, Nahum

doi:10.1038/nm1001-1128

Cited by 350 publications

(301 citation statements)

References 28 publications

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“…A comparison of the amounts of GAPDH mRNA Brown adipocytes of the white fat in culture L Lehr et al and protein in BAT B and WAT B shows comparable translation efficiency in both types of cells, suggesting that the low translation efficiency of UCP1 and of PGC-1a mRNAs in BAT B cells is specific. The translational inhibitor, 4E-BP1, which has been shown to induce a preferential decrease in the translation of a subset of mRNAs including PGC-1a, 30 might play a role in the specificity of the phenomenon. The high relative expression of UCP1 protein in the WAT B cells show that the latter should be considered as brown adipocyte-like cells.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…ectopic uncoupling protein 1 expression in WAT induces obesity resistance in mice (34) ; mice lacking insulin receptor only in BAT become diabetic (35) ; murine strains prone to develop obesity and diabetes have less BAT than obesity-and diabetes-resistant mice (35,37) ; obese rats treated with b3-agonists control obesity and diabetes and develop BAT (38)(39)(40)(41) ; many different models of transgenic mice with a clear brown phenotype of adipose organ are lean and obesity resistant (42)(43)(44) ; human subjects with more brown phenotype of abdominal subcutaneous fat have less insulin resistance then those showing a reduced brown phenotype (45) ; brown fat genes are reduced in visceral depots of obese individuals (46) .…”

Section: The Reversible Transdifferentiation Phenomenonmentioning

confidence: 99%

Reversible physiological transdifferentiation in the adipose organ

Cinti

2009

Proc. Nutr. Soc.

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All mammals are provided with two distinct adipose cells, white and brown adipocytes. White adipocytes store lipids to provide fuel to the organism, allowing intervals between meals. Brown adipocytes use lipids to produce heat. Previous descriptions have implied their localization in distinct sites of the body; however, it has been demonstrated that they are present together in many depots, which has led to the new concept of the adipose organ. In order to explain their coexistence the hypothesis of reversible physiological transdifferentiation has been developed, i.e. they are contained together because they are able to convert, one into the other. In effect, if needed the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ is associated with resistance to obesity and its related disorders. A new example of reversible physiological transdifferentiation of adipocytes is offered by the mammary gland during pregnancy, lactation and post-lactation stages. The gravidic hormonal stimulus seems to trigger a transdifferentiation of adipocytes into milk-producing and secreting epithelial glands. In the post-lactation period some of the epithelial cells of the mammary gland seem to transdifferentiate into adipocytes. Recent unpublished results suggest that explanted adipose tissue, as well as explanted isolated mature adipocytes, is able to transdifferentiate into glands with epithelial markers of milk-secreting mammary glands. These findings, if confirmed, seem to suggest new windows into the cell biology frontiers of adipocytes.

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“…Consistent with this, WAT PGC-1 protein and UCP1 mRNA levels, as well as whole body energy expenditure, were increased, resulting in a decrease in body fat mass. 4E-BP1 therefore seems to be a specific repressor of UCP1 expression and can be considered a new player in the control of adipose tissue development and energy homeostasis [1].…”

Section: Introductionmentioning

confidence: 99%

Control of 4E‐BP1 expression in mouse brown adipose tissue by the β₃‐adrenoceptor

Lehr¹,

Kuehne²,

Arboit³

et al. 2004

FEBS Letters

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Knockout of the translation inhibitor 4E-BP1 induces an overexpression of uncoupling protein-1 (UCP1) [Nature Medicine 7 (2001) 1128. A possible inverse control of UCP1 and 4E-BP1 expressions in mouse brown adipose tissue was investigated. Cold-exposure, which increases the expression of UCP1, decreased that of 4E-BP1 mRNA in wild type but not in b 1 =b 2 =b 3 -adrenoceptor knockout mice. Administration of the b 3 -adrenoceptor agonist CL 316 246 decreased 4E-BP1 mRNA by 75% and protein by 41% after 6 and 48 h, respectively. Our data are the first report of a regulation by the b 3 -adrenoceptor of 4E-BP1 expression. They support a role of the latter in adaptive thermogenesis.

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Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1

Cited by 350 publications

References 28 publications

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

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

Reversible physiological transdifferentiation in the adipose organ

Control of 4E‐BP1 expression in mouse brown adipose tissue by the β₃‐adrenoceptor

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Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1

Cited by 350 publications

References 28 publications

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

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

Reversible physiological transdifferentiation in the adipose organ

Control of 4E‐BP1 expression in mouse brown adipose tissue by the β3‐adrenoceptor

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Control of 4E‐BP1 expression in mouse brown adipose tissue by the β₃‐adrenoceptor