Modulation of <i>obese</i> gene expression in rat brown and white adipose tissues

Moinat, Madelaine; Deng, Chunhua; Muzzin, Patrick; Assimacopoulos-Jeannet, F.; Seydoux, Josiane; Dulloo, Abdul G.; Giacobino, Jean‐Paul

doi:10.1016/0014-5793(95)01030-i

Cited by 134 publications

(129 citation statements)

References 16 publications

(23 reference statements)

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“…In this study, the mRNA levels of the two hallmark genes of the WAT, leptin and resistin [22][23][24][25] were also much higher in the BAT B than in the WAT B adipocytes. The relatively low expression of the brown and white adipocyte hallmark genes was not a general feature of the WAT B adipocytes as the levels of expression of necdin 27 and of the reference gene cyclophilin A were similar in both the BAT B and the WAT B adipocytes.…”

Section: Discussionsupporting

confidence: 47%

“…[22][23][24][25] Necdin, which inhibits brown fat differentiation, 26 is expressed at a higher level in proliferating brown than white pre-adipocytes, but at the same level in mature brown and white adipocytes. 27 As shown in Figure 3, the WAT B adipocytes exhibited levels of leptin and resistin mRNA that were relatively low, amounting only 2.2 and 3.5%, respectively, of those in the BAT B adipocytes.…”

Section: Resultsmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 47%

Section: Resultsmentioning

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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“…However, fa/fa rats are remarkably insensitive to stimuli that reduce leptin levels in lean animals. 13,18±20 In addition, the fa/fa rat is presumed to be hyperphagic at least in part because of lack of central sensitivity to its own elevated leptin levels. 19±23 Thus, because of resistance to changes in leptin levels and to central effects of leptin itself any potential effect of CLtreatment to modify feeding via changes in leptin levels would not be sensed centrally and thus would not have any in¯uence on feeding behavior.…”

Section: Discussionmentioning

confidence: 99%

Appearance of brown adipocytes in white adipose tissue during CL 316,243-induced reversal of obesity and diabetes in Zucker fa/fa rats

1997

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BACKGROUND: In our previous studies, chronic treatment of rats with a new b b 3 -adrenoceptor agonist, CL 316,243, retarded diet-induced obesity and promoted thermogenesis in young animals and reversed established diet-induced obesity in older animals that continued to eat a high fat diet. Reversal of obesity was associated with shrinking of enlarged white adipocytes but the number of mature white adipocytes, which had not been increased by the diet, was not reduced. Drug-treatment induced appearance of abundant brown adipocytes in white adipose tissue (WAT) depots as well as hypertrophy of brown adipose tissue (BAT) in both lean and diet-induced obese rats. OBJECTIVES: To ®nd out whether the known hyperplasia of white adipocytes in the obese fa/fa rat could be reversed by CL 316,243-treatment and whether the grossly enlarged WAT depots of the obese fa/fa rat contain precursors to brown adipocytes. RESULTS: CL 316,243 infusion (1 mg/kg/d) reduced abdominal fat. The loss of fat was due to a decrease in white adipocyte size, with no loss of the markedly elevated number of adipocytes in the fa/fa rats. Resting metabolic rate increased by 40% in lean rats, by 70% in fa/fa rats. Food intake decreased in the hyperphagic fa/fa rats but did not change in lean rats. In both lean and fa/fa rats, a marked increase in protein content of retroperitoneal WAT was associated with appearance of abundant densely-stained brown adipocytes expressing uncoupling protein (UCP) but total number of cells (from DNA content) actually decreased. Hyperinsulinemia and hyperglycemia of fa/fa rats were reduced by treatment, indicating improved sensitivity to insulin. CONCLUSIONS: Abundant precursors to brown adipocytes are present in WAT depots of fa/fa rats and much of the exaggerated increase in resting metabolic rate induced by CL 316,243 occurs in these cells. This b b 3 -adrenoceptor agonist is an effective anti-obesity and anti-diabetic agent in fa/fa rats. It does not bring about disappearance of mature white adipocytes but does bring about a remodelling of WAT, with a marked change in cell composition.

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“…In addition, OB protein is homologous to the class I cytokine family (8). Finally, the ob gene is expressed only in adipose tissues, mainly in white, but also in brown adipose tissue (9,10) in proportion to adipocyte size and number (5).…”

Section: General Properties Of Ob Proteinmentioning

confidence: 99%

Pivotal role of leptin in insulin effects

Ceddia

William

Lima

et al. 1998

Braz J Med Biol Res

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The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms) have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

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Modulation of obese gene expression in rat brown and white adipose tissues

Cited by 134 publications

References 16 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

Appearance of brown adipocytes in white adipose tissue during CL 316,243-induced reversal of obesity and diabetes in Zucker fa/fa rats

Pivotal role of leptin in insulin effects

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