Enlargement of Interscapular Brown Adipose Tissue in Growth Hormone Antagonist Transgenic and in Growth Hormone Receptor Gene-Disrupted Dwarf Mice

2003 ◽  
Vol 228 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Yuesheng Li ◽  
Joanne R. Knapp ◽  
John J. Kopchick
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Northern Analysis ◽  
Interscapular Brown Adipose Tissue ◽  
Triglyceride Accumulation ◽  
Brown Adipose ◽  
Dwarf Mice

Growth hormone (GH) acts on adipose tissue by accelerating fat expenditure, preventing triglyceride accumulation, and facilitating lipid mobilization. To investigate whether GH is involved in the development and metabolism of interscapular brown adipose tissue (BAT), a site of nonshivering thermogenesis, we employed three lines of transgenic mice. Two of the lines are dwarf due to expression of a GH antagonist (GHA) or disruption of the GH receptor/binding-protein gene. A third mouse line is giant due to overexpression of a bovine GH (bGH) transgene. We have found that the body weights of those animals are proportional to their body lengths at 10 weeks of age. However, GHA dwarf mice tend to catch up with the nontransgenic (NT) littermates in body weight but not in body length at 52 weeks of age. The increase of body mass index (BMI) for GHA mice accelerates rapidly relative to controls as a function of age. We have also observed that BAT in both dwarf mouse lines but not in giant mice is enlarged in contrast to nontransgenic littermates. This enlargement occurs as a function of age. Northern analysis suggests that BAT can be a GH-responsive tissue because GHR/BP mRNAs were found there. Finally, the level of uncoupling protein-1 (UCP1) RNA was found to be higher in dwarf mice and lower in giant animals relative to controls, suggesting that GH-mediated signaling may negatively regulate UCP1 gene expression in BAT.

scholarly journals Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia

1993 ◽  
Vol 291 (1) ◽  
pp. 109-113 ◽  
Author(s):  
R Burcelin ◽  
J Kande ◽  
D Ricquier ◽  
J Girard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Time Course ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Diabetic Rats ◽  
Plasma Insulin Concentration ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene.

Glucocorticoids and regulation of brown adipose tissue in humans – physiological and pathophysiological considerations

2017 ◽  
Vol 86 (3) ◽  
pp. 227
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Adrenergic Stimulation ◽  
Therapeutic Goals ◽  
Bat Activity ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Differentiation And Proliferation

This review discusses the effects of glucocorticoids (GCs) on brown adipose tissue (BAT) in the context of obesity prevention and therapy. Due to the unique expression of the uncoupling protein 1 (UCP1), BAT is capable of non‑shivering thermogenesis, also defined as a metabolic heat production, related to increased metabolic rate. All processes that contribute to an increase in activity and/or quantity of BAT are able to upturn metabolism, and thus enable the above therapeutic goals to be achieved. GCs may stimulate BAT differentiation and proliferation. In the case of differentiation, the opposite effect of GCs has been also described. Within white adipose tissue (WAT) GCs inhibit the formation of so called beige adipocytes that are functionally and morphologically similar to the adipocytes from BAT. The activity of GCs with concomitant inhibition of WAT browning is mediated by the induction of microRNA-27b (MIR27B) expression. GCs are responsible for the decline in BAT activity as the body ages. Depriving the body of an enzyme responsible for local reduction of cortisone into an active GC‑cortisol in BAT (11β‑hydroxysteroid dehydrogenase type 1; 11β‑HSD1) prevents the reduction of BAT activity. The effects of high doses of GCs on BAT generally depend on the exposure time. Prolonged elevation in GCs level decreases BAT activity. During adrenergic stimulation the effect of GCs on BAT is ambiguous, because both decrease and increase in activity has been described. A full understanding of the GCs impact on brown remodeling in WAT may reveal a discovery of a novel preventive and therapeutic strategies for obesity and possibly other metabolic disorders.

scholarly journals Thermogenic and lipogenic activities in brown adipose tissue of I-strain mice

1985 ◽  
Vol 231 (3) ◽  
pp. 761-764 ◽  
Author(s):  
R Bazin ◽  
D Ricquier ◽  
F Dupuy ◽  
J Hoover-Plow ◽  
M Lavau
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Fatty Acid Synthetase ◽  
Food Utilization ◽  
Lower Efficiency ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

The thermogenic capacity of brown adipose tissue has been investigated in I-strain mice to determine whether this tissue could play a role in the lower efficiency of food utilization reported in this strain of mice. (1) As compared with C57BL mice (a control strain), interscapular-brown-adipose-tissue weight and lipid percentage were decreased by 40% and 13% respectively in I-strain mice. (2) Mitochondrial protein content and cytochrome c oxidase activity were similar in the two strains, but the number of mitochondrial GDP-binding sites and uncoupling-protein content were increased by 2-fold in I-strain mice. (3) Fatty acid synthetase and citrate-cleavage enzyme (units/mg of protein) were 3-fold higher in the brown adipose tissue of I-strain mice. These results indicate that I-strain mice possess a very active brown adipose tissue. This enhanced capacity of energy dissipation in brown adipose tissue could contribute to the decreased capacity of I-strain mice to store adipose tissue.

scholarly journals Hypothalamic Melanin-Concentrating Hormone Is Induced by Cold Exposure and Participates in the Control of Energy Expenditure in Rats

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4831-4840 ◽  
Author(s):  
Márcio Pereira-da-Silva ◽  
Márcio A. Torsoni ◽  
Hugo V. Nourani ◽  
Viviane D. Augusto ◽  
Cláudio T. Souza ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Tissue Mass ◽  
Interscapular Brown Adipose Tissue ◽  
Cdna Macroarray ◽  
Adaptation To Cold ◽  
Brown Adipose ◽  
Melanin Concentrating Hormone

Abstract Short-term cold exposure of homeothermic animals leads to higher thermogenesis and food consumption accompanied by weight loss. An analysis of cDNA-macroarray was employed to identify candidate mRNA species that encode proteins involved in thermogenic adaptation to cold. A cDNA-macroarray analysis, confirmed by RT-PCR, immunoblot, and RIA, revealed that the hypothalamic expression of melanin-concentrating hormone (MCH) is enhanced by exposure of rats to cold environment. The blockade of hypothalamic MCH expression by antisense MCH oligonucleotide in cold-exposed rats promoted no changes in feeding behavior and body temperature. However, MCH blockade led to a significant drop in body weight, which was accompanied by decreased liver glycogen, increased relative body fat, increased absolute and relative interscapular brown adipose tissue mass, increased uncoupling protein 1 expression in brown adipose tissue, and increased consumption of lean body mass. Thus, increased hypothalamic MCH expression in rats exposed to cold may participate in the process that allows for efficient use of energy for heat production during thermogenic adaptation to cold.

scholarly journals Brown adipose tissue development and function and its impact on reproduction

2018 ◽  
Vol 238 (1) ◽  
pp. R53-R62 ◽  
Author(s):  
Michael E Symonds ◽  
Peter Aldiss ◽  
Neele Dellschaft ◽  
James Law ◽  
Hernan P Fainberg ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Maternal Obesity ◽  
Thermal Environment ◽  
Uncoupling Protein ◽  
The Body ◽  
Substantial Impact ◽  
Brown Adipose ◽  
Fat Depot

Although brown adipose tissue (BAT) is one of the smallest organs in the body, it has the potential to have a substantial impact on both heat production as well as fat and carbohydrate metabolism. This is most apparent at birth, which is characterised with the rapid appearance and activation of the BAT specific mitochondrial uncoupling protein (UCP)1 in many large mammals. The amount of brown fat then gradually declines with age, an adaptation that can be modulated by the thermal environment. Given the increased incidence of maternal obesity and its potential transmission to the mother’s offspring, increasing BAT activity in the mother could be one mechanism to prevent this cycle. To date, however, all rodent studies investigating maternal obesity have been conducted at standard laboratory temperature (21°C), which represents an appreciable cold challenge. This could also explain why offspring weight is rarely increased, suggesting that future studies would benefit from being conducted at thermoneutrality (~28°C). It is also becoming apparent that each fat depot has a unique transcriptome and show different developmental pattern, which is not readily apparent macroscopically. These differences could contribute to the retention of UCP1 within the supraclavicular fat depot, the most active depot in adult humans, increasing heat production following a meal. Despite the rapid increase in publications on BAT over the past decade, the extent to which modifications in diet and/or environment can be utilised to promote its activity in the mother and/or her offspring remains to be established.

scholarly journals The effect of maternal prolactin infusion during pregnancy on fetal adipose tissue development

2002 ◽  
Vol 174 (3) ◽  
pp. 427-433 ◽  
Author(s):  
H Budge ◽  
A Mostyn ◽  
V Wilson ◽  
A Khong ◽  
AM Walker ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Neonatal Rat ◽  
Postnatal Life ◽  
Voltage Dependent Anion Channel ◽  
Tissue Samples ◽  
Interscapular Brown Adipose Tissue ◽  
Rat Pups ◽  
Brown Adipose

The present study determines whether maternal administration of prolactin (PRL) to dams promotes the abundance of the brown adipose tissue-specific uncoupling protein-1 (UCP1) in fetal and neonatal rat pups. Recombinant PRL (24 micro g/kg per day), or an equivalent volume of saline, were infused into dams (n=19 per group) throughout pregnancy from 12 h after mating. Interscapular brown adipose tissue was sampled either from fetuses at 19.5 days of gestation (term=21.5 days) or from neonatal rat pups at approximately 18 h after birth. The abundance of UCP1 was determined by immunoblotting on adipose tissue samples from individual pups and pooled from groups of pups. This analysis was complemented by immunocytochemistry on representative adipose tissue samples. Maternal PRL infusion resulted in a greater abundance of UCP1 in fetal rats at 19.5 days of gestation (control: 97.2+/-8.4% reference; PRL: 525.6+/-74.4% reference; P<0.001) and in neonates 18 h after birth. In contrast, the abundance of the outer mitochondrial membrane protein voltage-dependent anion channel was unaffected by PRL. Neonatal adipose tissue sampled from pups born to PRL-infused dams possessed fewer lipid droplets, but more UCP1, as determined by immunocytochemistry. Fetal, but not maternal, plasma leptin concentrations were also increased by maternal PRL administration. In conclusion, as rats are altricial, and the potential thermogenic activity of brown adipose tissue develops over the first few days of postnatal life, these changes prior to, and at the time of, birth implicate PRL in fetal and neonatal adipose tissue maturation.

Evidence against a Mediatory Role of Brown Adipose Tissue in the Calorigenic Response of Cold-Acclimated Rats to Noradrenaline

1974 ◽  
Vol 52 (6) ◽  
pp. 1051-1062 ◽  
Author(s):  
David O. Foster
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
The Body ◽  
Albino Rats ◽  
Interscapular Brown Adipose Tissue ◽  
Unique Role ◽  
Brown Adipose ◽  
Colonic Temperature ◽  
Vascular Connections

The calorigenic response to infused noradrenaline (NA) of barbital-anesthetized, cold-acclimated, adult, gnotobiotic, albino rats tested 1 h after removal of interscapular brown adipose tissue (I.B.A.T.) was 14% lower than before surgery and 15% lower than the response of either sham-operated or non-operated rats; but 4 days later, the response of rats without I.B.A.T. was not significantly different from that of the controls. In unanesthetized rats, response to NA was also unaffected by interruption of blood flow to I.B.A.T. 1–3 days before the measurements. Since these results do not conform with previous findings of 30–60% reductions in response to NA following removal of I.B.A.T. or interference with the tissue's vascular connections, they contradict the current hypothesis that the B.A.T. of cold-acclimated rodents has a unique role as a mediator of calorigenesis in other tissues.A supplementary feature of the study was the discovery of apparent thermolability in the process by which cold-acclimated rats respond calorigenically to NA. If, during infusion of NA, colonic temperature exceeded about 41.5 °C, an apparently critical degree of hyperthermia response to the hormone during a subsequent infusion was reduced. This reduction was linearly related to the previous maximum colonic temperature over the range 41.6–42.4 °C and amounted to approximately 70% at 42.4 °C. These results indicate the necessity for monitoring the body temperatures of animals during infusion of NA, particularly in experiments in which two or more tests of response to NA are done on the same animal. Since such temperature measurements were not reported in those studies that have suggested a mediatory role of B.A.T. in calorigenesis in rodents, it is not possible to resolve the discrepancies on this basis.

Adrenergically stimulated blood flow in brown adipose tissue is not dependent on thermogenesis

2015 ◽  
Vol 308 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Gustavo Abreu-Vieira ◽  
Carolina E. Hagberg ◽  
Kirsty L. Spalding ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Temperature Acclimation ◽  
The Body ◽  
Doppler Imaging ◽  
Dependent Manner ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis relies on blood flow to be supplied with nutrients and oxygen and for the distribution of the generated heat to the rest of the body. Therefore, it is fundamental to understand the mechanisms by which blood flow is regulated and its relation to thermogenesis. Here, we present high-resolution laser-Doppler imaging (HR-LDR) as a novel method for noninvasive in vivo measurement of BAT blood flow in mice. Using HR-LDR, we found that norepinephrine stimulation increases BAT blood flow in a dose-dependent manner and that this response is profoundly modulated by environmental temperature acclimation. Surprisingly, we found that mice lacking uncoupling protein 1 (UCP1) have fully preserved BAT blood flow response to norepinephrine despite failing to perform thermogenesis. BAT blood flow was not directly correlated to systemic glycemia, but glucose injections could transiently increase tissue perfusion. Inguinal white adipose tissue, also known as a brite/beige adipose tissue, was also sensitive to cold acclimation and similarly increased blood flow in response to norepinephrine. In conclusion, using a novel noninvasive method to detect BAT perfusion, we demonstrate that adrenergically stimulated BAT blood flow is qualitatively and quantitatively fully independent of thermogenesis, and therefore, it is not a reliable parameter for the estimation of BAT activation and heat generation.

Nonshivering thermogenesis and the thermogenic capacity of brown fat in fasted and/or refed mice

1988 ◽  
Vol 254 (1) ◽  
pp. R11-R16 ◽  
Author(s):  
P. Trayhurn ◽  
G. Jennings
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Nonshivering Thermogenesis ◽  
Interscapular Brown Adipose Tissue ◽  
Cytochrome Oxidase Activity ◽  
Brown Adipose ◽  
Thermogenic Capacity

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.

Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe

1988 ◽  
Vol 75 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Frédéric Bouillaud ◽  
Francesc Villarroya ◽  
Eliane Hentz ◽  
Serge Raimbault ◽  
Anne-Marie Cassard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Genomic Library ◽  
Uncoupling Protein ◽  
Molecular Probes ◽  
Molecular Probe ◽  
Single Type ◽  
Northern Analysis ◽  
Brown Adipose ◽  
Human Genomic

1. Studies on human brown adipose tissue require specific molecular probes. A human genomic library has been screened with a complementary DNA corresponding to the uncoupling protein (UCP) of rat brown adipose tissue mitochondria. 2. Two recombinant phages were isolated, carrying genomic sequences of human UCP. From them we have subcloned a 0.5 kilobase fragment. This fragment, H-Ucp-0.5, contained two intronic regions and two exonic regions. Exonic regions encoded a sequence of 84 amino acids which exhibited a strong homology with central domain at rat UCP. The organization of H-Ucp-0.5 was confirmed by SI mapping analysis. 3. A Southern analysis suggested that the gene is single type in the human, as it is in rodents. 4. In Northern analysis experiments, H-Ucp-0.5 detected a specific 1.8 kb mRNA in human brown adipose tissue obtained from six patients with phaeochromocytoma and from one patient with a hibernoma. This molecular probe is a new, sensitive and reliable tool with which to study human brown adipocytes.

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