Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue

Giralt, Marta; Martín, Isabel Fernández de Castro; Iglesias, Roser; Viñas, Octavi; Villarroya, Francesc; Mampel, Teresa

doi:10.1111/j.1432-1033.1990.tb19336.x

Cited by 75 publications

(67 citation statements)

References 28 publications

(1 reference statement)

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“…29,30 As described in the literature, we found that UCP-1 mRNA was induced at day 20 of the gestation and that its level suddenly increased at birth ( Figure 4B). The BUG transcript appeared much earlier as it was already detectable at a low level in interscapular BAT of 18-day-old foetuses ( Figure 4B).…”

Section: Resultsmentioning

confidence: 49%

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Cloning of BUG demonstrates the existence of a brown preadipocyte distinct from a white one

et al. 2001

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BACKGROUND: Several indirect arguments agree with the existence of a brown preadipocyte distinct from a white one. Nevertheless, to date, no molecular marker has been available to directly in vivo demonstrate this hypothesis. OBJECTIVE: The aim of this study was to find a gene expressed in brown preadipocyte but not in white and to use it as a molecular marker to analyse brown preadipocyte recruitment in different physiological and physiopathological situations. METHOD: Differential display was performed on stromal-vascular and adipocyte fractions of white and brown adipose tissues in rat. RESULTS: We identified a new gene, BUG, preferentially expressed in the stromal-vascular fraction of brown fat vs other adipose tissues fractions in adult rat. This RNA is also highly expressed in heart and, to a lesser extent, in other tissues such as kidney and brain. The BUG transcript is detected by in situ hybridization in putative preadipocytes within brown adipose tissue. Its level is transiently and specifically up-regulated during early stages of brown preadipocyte differentiation in a primary culture system, before the acquisition of late brown adipocyte phenotype. During development, BUG can be detected before the emergence of UCP-1 expression. In adult rats, BUG expression is inversely associated to brown adipose tissue (BAT) activation during cold exposure as well as in obese animals. CONCLUSIONS: The pattern of BUG expression agrees with an early divergence between brown and white adipocyte lineages. It also reveals the existence of a pool of committed brown preadipocytes within BAT that are recruited during cold exposure. BUG expression is increased in obese animals, suggesting that an early defect in brown preadipocyte differentiation could account for impaired BAT function in genetically obese rats.

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Section: Resultsmentioning

confidence: 49%

“…29 UCP-1 mRNA appears at 19 days of gestation and suddenly increases at birth. 30 In comparison, BUG transcript was already present in foetuses before the detection of UCP-1, as in primary culture. This suggests that the divergence between white and brown preadipocytes takes place at the very beginning of BAT development.…”

Section: Discussionmentioning

confidence: 99%

Cloning of BUG demonstrates the existence of a brown preadipocyte distinct from a white one

et al. 2001

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“…UCP-1, a unique mitochondrial protein that uncouples oxidative phosphorylation from the respiratory chain is a marker specific for brown adipose tissue differentiation (1). UCP-1 mRNA was expressed at low levels at embryonic day 19.5.…”

Section: Expression Of Fgf-16 Mrna In Rat Embryonicmentioning

confidence: 99%

“…Brown adipose tissue is a specialized tissue of mammals responsible for facultative thermogenesis (1). Proliferation and differentiation of brown adipose tissue occurs during the embryonic period (1,12).…”

Section: Fgf-16 In Brown Adipose Tissuementioning

confidence: 99%

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Fibroblast Growth Factor-16 Is a Growth Factor for Embryonic Brown Adipocytes

Konishi

Mikami

Yamasaki

et al. 2000

Journal of Biological Chemistry

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In rat embryos, fibroblast growth factor (FGF)-16 is predominantly expressed in brown adipose tissue. To elucidate the role of FGF-16, we examined the expression of FGF-16 mRNA in rat embryonic brown adipose tissue at different developmental stages by Northern blotting analysis and in situ hybridization. FGF-16 mRNA was expressed abundantly in brown adipose tissue during embryonic day 17.5, embryonic days 17.5-19.5, and thereafter at lower levels into the neonatal period. The expression profile of FGF-16 mRNA well corresponds to the proliferative profile of embryonic brown adipose tissue reported. We also examined the mitogenic activity of recombinant rat FGF-16 for primary brown adipocytes prepared from rat embryonic brown adipose tissue. FGF-16 showed significant mitogenic activity for primary brown adipocytes. The mitogenic activity was found to be exerted by binding and activating FGF receptor-4 in the brown adipose tissue. As a great induction of proliferation of rat brown adipose tissue during cold acclimation was reported, we also examined the expression of FGF-16 mRNA in the brown adipose tissue during cold acclimation by Northern blotting analysis. The expression of FGF-16 mRNA was not increased, but rather decreased. The expression profile of FGF-16 mRNA and the mitogenic activity of FGF-16 reported here indicate that FGF-16 is a unique growth factor involved in proliferation of embryonic brown adipose tissue.Adipose tissues serve an important function in the energy economy of vertebrate organisms by providing a massive energy reserve that can be mobilized upon demand. There are two types of adipose tissues, white and brown. Their physiological roles are quite different. White adipose tissue stores energy, whereas brown adipose tissue dissipates energy. Brown adipose tissue is a specialized tissue of mammals responsible for facultative thermogenesis. Its physiological significance has been recognized in newborns when the decrease in environmental temperature at birth requires an adaptive increase in heat production (1). Brown adipose tissue is also speculated to normally function to prevent obesity. Indeed, transgenic mice with primary deficiency of brown adipose tissue have obesity, which develops in the absence of hyperphagia. As obesity progresses, transgenic animals develop hyperphagia (2). These results support a critical role for brown adipose tissue in the nutritional homeostasis of mice.The prototypic fibroblast growth factors (FGFs), 1 FGF-1 (acidic FGF) and FGF-2 (basic FGF), were originally isolated from the brain and pituitary as mitogens for fibroblasts (3, 4). The FGF family now consists of 19 members, FGF-1 to FGF-19 (5, 6). FGFs are widely expressed in developing and adult tissues and appear to have important roles with multiple biological activities, including angiogenesis, mitogenesis, cellular differentiation, and repair of tissue injury (3,4,7,8). In rat embryos, FGF-16 mRNA was predominantly expressed in brown adipose tissue, indicating that FGF-16 plays a unique role in embryonic ...

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Inhibition of PI 3-kinase and RAS blocks IGF-I and insulin-induced uncoupling protein 1 gene expression in brown adipocytes

et al. 1998

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Fetal brown adipocytes expressed uncoupling protein 1 (UCP1) mRNA, this expression being blunted throughout culture for 24 h in a serum-free medium. At physiological doses, either insulin-like growth factor I (IGF-I) or insulin turned out to be as potent as dibutyryl cAMP (dbcAMP) in increasing UCP1 gene transcription rate (1 h) and also UCP1 mRNA accumulation (3 h), their maximal effect (15-fold increase) reached upon treatment for 24 h. Upon treatment with either IGF-I or insulin for 48 h, a 7-fold increase in the UCP1 protein content relative to levels in the control cells was found, this induction being abolished in the presence of cycloheximide. Moreover, either IGF-I or insulin transactivates the UCP1-chloramphenicol acetyl transferase (CAT) fusion gene after transient transfection of primary brown adipocytes, these effects being tissue-specific. Transient transfection of dominant-negative form of phosphatidylinositol (PI) 3-kinase completely blocked the transactivation of the fusion gene UCP1-CAT induced by either IGF-I or insulin, although inhibition of p70S6kinase with rapamycin does not preclude transactivation of the UCP1 promoter by insulin. Furthermore, transient transfection of dominant-negative form of p21-ras or treatment of cells with a mitogen-activated protein kinase kinase (MEK-1) inhibitor (PD098059) completely abolished insulin-induced UCP1-CAT transactivation. Cotransfection with dominant-negative p85 or with dominant-negative Ras also produced down-regulation of the insulin or IGF-I-induced 12-O-tetradecanoylphorbol-13-acetate response element (TRE)-CAT (five AP-1, activating protein-1, binding sites arranged in tandem) transactivation. In addition, insulin induced AP-1 DNA binding activity, this effect being totally prevented in the presence of MEK-1 inhibitor. These results strongly suggest that either IGF-I or insulin induced thermogenic-differentiation through AP-1 activity in a PI 3-kinase and Ras/MAPK dependent manner in brown adipocytes.

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Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue

Cited by 75 publications

References 28 publications

Cloning of BUG demonstrates the existence of a brown preadipocyte distinct from a white one

Cloning of BUG demonstrates the existence of a brown preadipocyte distinct from a white one

Fibroblast Growth Factor-16 Is a Growth Factor for Embryonic Brown Adipocytes

Inhibition of PI 3-kinase and RAS blocks IGF-I and insulin-induced uncoupling protein 1 gene expression in brown adipocytes

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