An immunohistochemical and in situ hybridisation study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue

Finn, D.; Lomax, M.A.; Trayhurn, Paul

doi:10.1007/s004410051197

Cited by 21 publications

(15 citation statements)

References 22 publications

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“…At a molecular level, this change can be followed by the increased expression during fetal life of the BAT marker gene uncoupling protein 1 (UCP1), which confers the thermogenic function of this tissue (7). Our studies in the ovine have demonstrated that expression of UCP1 in perirenal adipose tissue (PAT) is totally suppressed within 5 d after birth despite being born into an environmental temperature below the thermoneutral zone (8). Attempts to reinduce UCP1 expression in the ovine by administration of a ␤ 3 -adrenoreceptor agonist during the first month of life have been met with limited success (9,10), agreeing with the morphological and thermogenic activity evidence that ovine BAT is irreversibly transformed to WAT during the first weeks of life (2,11).…”

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confidence: 88%

Ontogenic Loss of Brown Adipose Tissue Sensitivity to β-Adrenergic Stimulation in the Ovine

Lomax¹,

Sadiq²,

Karamanlidis³

et al. 2007

Endocrinology

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In ruminants and other large animals, expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT) is confined to the perinatal period when it plays a key role in nonshivering thermogenesis. This study determined whether loss of expression of the BAT phenotype was due to reduced response to a beta-agonist, isoprenaline, and expression of the peroxisome proliferator-activated receptor (PPAR) family [PPARalpha, PPARgamma, PPAR coactivator 1alpha (PGC-1alpha)], which regulates UCP1 gene expression. Perirenal adipose tissue (PAT) was sampled from ovine fetuses, newborn lambs, and lambs on d 1, 5, 7, and 21 of life. UCP1 mRNA and protein in PAT increased from d 123 of fetal life to reach a maximum at birth followed by a rapid decrease over the first 5 d of life. Expression of the coactivator, PGC-1alpha and PPAR alpha, peaked between fetal day 123 and birth, and then declined to undetectable levels in the first days of life. In vivo administration of isoprenaline was able to induce expression of UCP1, PGC-1alpha, and PPARalpha in BAT up to 5 d of age but thereafter was ineffective. In vitro addition of beta-receptor, PPARalpha, and PPARgamma agonists were unable to overcome the suppression of UCP1, PPARalpha, and PPARgamma expression observed in differentiated adipocytes prepared from 30-d-old compared with 1-d-old lambs. These data are consistent with a model in which postnatal loss of UCP1 expression and beta-adrenergic induction of the brown adipocyte phenotype is due to loss of expression of PGC-1alpha and PPARalpha.

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confidence: 88%

Ontogenic Loss of Brown Adipose Tissue Sensitivity to β-Adrenergic Stimulation in the Ovine

Lomax¹,

Sadiq²,

Karamanlidis³

et al. 2007

Endocrinology

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“…BAT is detected in newborns but its thermogenic activity decreases rapidly after birth (21). In young humans, BAT seems to be converted into white adipose tissue as has been described for ruminants (22,23). However, it is possible to detect BAT in certain conditions: in outdoor workers exposed to cold conditions (24) or in several pathological situations such as pheochromocytoma or hibernoma (21,25,26).…”

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confidence: 99%

Transcriptional Activation of the Human ucp1 Gene in a Rodent Cell Line

Barroso¹,

Pecqueur²,

Gelly

et al. 2000

Journal of Biological Chemistry

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Uncoupling protein 1 (UCP1) is uniquely expressed in brown adipocytes and generates heat production by uncoupling respiration from ATP synthesis. The activatory effects of norepinephrine and retinoic acid (RA) on rodent ucp1 gene transcription have been well characterized. These effects are mediated by a 211-base pair (bp) enhancer which is also sufficient to restrict expression to brown adipose tissue. The molecular mechanisms controlling the transcription of the human ucp1 gene are unknown. In order to study the transcriptional regulation of the human gene, we set up chloramphenicol acetyltransferase constructs containing the entire or deleted 5 regions upstream of the transcriptional start site of the gene. These constructs were transiently transfected in a mouse cell line. A 350-bp hormone response region showing a significant homology with the rat ucp1 enhancer and located between the BclI polymorphic site and an AatII site (bp ؊3820/؊3470) was detected. This region was sufficient to mediate the stimulation by RA and by combined treatments (RA ؉ isoproterenol (ISO), RA ؉ thiazolidinedione (TZD), or RA ؉ ISO ؉ TZD). The highest stimulation, a 26-fold increase in basal activity, was obtained by RA ؉ ISO ؉ TZD treatment. In contrast to the rodent gene, under our conditions, the effect of ISO and/or TZD is dependent on RA stimulation. Analysis of 105 bp inside the 350-bp element by site-directed mutagenesis and gel retardation experiments demonstrated that a multipartite response element mediates the drug stimulation. This region binds RARs and RXRs nuclear factors, CREB/ATF factors, and also PPAR␥ despite the absence of a consensus peroxisome-proliferator response element. The activation of the human ucp1 gene transcription by certain hormones or drugs, and the identification of the cis-elements involved, will help to identify new compounds activating fat oxidation and energy expenditure in humans.

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“…Uncoupling protein (UCP)1, a 32-kDa protein in the inner mitochondrial membrane and exclusively found in BAT, appears in the fetus around midgestation (4), and thereafter its expression in perirenal adipose tissue increases up to term before rapidly declining so that it is undetectable by the end of the first month after birth (5). Gene expression of UCP1 is nutritionally regulated, at least in part, and is downregulated in response to late-gestation maternal nutrient restriction (6).…”

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confidence: 99%

Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation

et al. 2013

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Background: Brown adipose tissue (BAT) thermogenesis is essential for newborn survival. Pericardial adipose tissue is a visceral depot that promotes metabolic and cardiovascular adaptations. We determined whether BAT is present in pericardial adipose tissue in newborns and whether maternal nutrition during late gestation compromises BAT in the postnatal period. Methods: We measured uncoupling protein 1 (UCP1) and other BAT-specific genes (e.g., β3-adrenergic receptor (β3ADR) and deiodinase type 2 (DIO2)), together with markers of white adipose tissue (WAT) in sheep on either the first or 30th day after birth. These were twin offspring born to mothers fed with either 100% or nutrient restricted (NR) to 60% of their total metabolizable requirements from 110 d gestation to term. results: Gene expression of UCP1 and other BAT-related genes decreased significantly with age. In newborns, maternal nutrient restriction downregulated gene expression of DIO2 and the β3-adrenergic receptor with reduced UCP1 but had no effect on genes predominantly expressed in WAT. conclusion: BAT is present around the heart in newborns. Exposure to a suboptimal maternal diet in late gestation specifically compromises BAT development and has the potential to place these offspring at increased risk of hypothermia after birth without effects on the subsequent appearance of WAT.

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An immunohistochemical and in situ hybridisation study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue

Cited by 21 publications

References 22 publications

Ontogenic Loss of Brown Adipose Tissue Sensitivity to β-Adrenergic Stimulation in the Ovine

Ontogenic Loss of Brown Adipose Tissue Sensitivity to β-Adrenergic Stimulation in the Ovine

Transcriptional Activation of the Human ucp1 Gene in a Rodent Cell Line

Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation

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