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

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.

1992 ◽  
Vol 282 (1) ◽  
pp. 231-235 ◽  
Author(s):  
D M Smith ◽  
S R Bloom ◽  
M C Sugden ◽  
M J Holness

Starvation (48 h) decreased the concentration of mRNA of the insulin-responsive glucose transporter isoform (GLUT 4) in interscapular brown adipose tissue (IBAT) (56%) and tibialis anterior (10%). Despite dramatic [7-fold (tibialis anterior) and 40-fold (IBAT)] increases in glucose utilization after 2 and 4 h of chow re-feeding, no significant changes in GLUT 4 mRNA concentration were observed in these tissues over this re-feeding period. The results exclude changes in GLUT 4 mRNA concentration in mediating the responses of glucose transport in these tissues to acute re-feeding after prolonged starvation.


1987 ◽  
Vol 65 (11) ◽  
pp. 955-959 ◽  
Author(s):  
Hasmukh V. Patel ◽  
Karl B. Freeman ◽  
Michel Desautels

The time course of changes in the level of uncoupling protein mRNA when cold-acclimated mice were returned to a thermoneutral environment (33 °C) was examined using a cDNA probe. Upon deacclimation, there was a marked loss of uncoupling protein mRNA within 24 h, which precedes the loss of uncoupling protein from mitochondria. This loss of uncoupling protein mRNA was selective, since there was no change in the relative proportion of cytochrome c oxidase subunit IV mRNA or poly(A)+ RNA in total RNA. The results suggest that the decrease in the mitochondrial content of uncoupling protein during deacclimation is likely the result of turnover of existing protein, with very little replacement due to a lower level of its mRNA.


1999 ◽  
Vol 276 (1) ◽  
pp. R143-R151 ◽  
Author(s):  
Victoria L. King ◽  
Linda P. Dwoskin ◽  
Lisa A. Cassis

The neuronal uptake of norepinephrine (NE) in sympathetically innervated tissues is mediated by a high-affinity NE uptake transporter (NET). Rat interscapular brown adipose tissue (ISBAT) is densely innervated by the sympathetic nervous system for the control of cold- and diet-induced thermogenesis. To determine if cold exposure regulates the NET, kinetic parameters for [3H]NE uptake and [3H]nisoxetine (Nis) binding were determined in ISBAT from 7-day cold-exposed (CE) and control rats. Uptake of [3H]NE in ISBAT slices was of high affinity (1.6 μM). After 7 days of cold exposure the affinity for [3H]NE uptake was not altered; however, the uptake capacity was decreased (38%) in ISBAT slices from CE rats. Kinetic parameters for [3H]Nis binding demonstrated a single high-affinity site in ISBAT from CE and control rats with similar affinity. The density of [3H]Nis sites in ISBAT was decreased (38%) following cold exposure. A time course (2 h-7 days) for cold exposure demonstrated downregulation of [3H]Nis binding density by day 3, which remained through day 7. The affinity for [3H]Nis binding was transiently decreased at 2 h of cold exposure. Similarly, ISBAT NE content was decreased at 2 h of cold exposure. Pair feeding CE rats to food intake of controls normalized plasma NE content; however, [3H]Nis binding density in ISBAT remained decreased in pair-fed rats. These results demonstrate that the ISBAT NET is downregulated following cold exposure. Reductions in ISBAT NE content precede alterations in NET density; however, plasma NE content is not related to regulation of the NET.


1995 ◽  
Vol 268 (5) ◽  
pp. R1209-R1216 ◽  
Author(s):  
A. M. Strack ◽  
C. J. Horsley ◽  
R. J. Sebastian ◽  
S. F. Akana ◽  
M. F. Dallman

Glucocorticoids and insulin effect long-term reciprocal changes in food intake and body weight. We tested the interactions of corticosterone and insulin on caloric efficiency, white adipose tissue (WAT) stores, and brown adipose tissue (BAT). Two experiments were performed: 1) adrenalectomized rats were treated with corticosterone with or without streptozotocin-induced diabetes and 2) adrenalectomized, corticosterone-treated, diabetic rats were treated with insulin. By 4-5 days later, > or = 50% of the variance in caloric efficiency, plasma triglycerides, and WAT stores was explained by regression of these variables on corticosterone (catabolic) and insulin (anabolic). When the ratio of the hormones was normal, but concentrations high, overall gain of energy stores decreased and energy was redistributed to fat. Both hormones were anabolic on BAT lipid storage; the hormones played a complex role in the regulation of uncoupling protein (UCP) in BAT. Although corticosterone inhibited and insulin stimulated UCP, these effects were only evident in diabetics and with normoglycemia, respectively. For BAT variables, < or = 50% of the variance was explained by regression on corticosterone and insulin, suggesting that the effects of these hormones are mediated through an intermediate such as sympathetic nervous system input to BAT.


1985 ◽  
Vol 231 (3) ◽  
pp. 761-764 ◽  
Author(s):  
R Bazin ◽  
D Ricquier ◽  
F Dupuy ◽  
J Hoover-Plow ◽  
M Lavau

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.


2003 ◽  
Vol 228 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Yuesheng Li ◽  
Joanne R. Knapp ◽  
John J. Kopchick

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.


2012 ◽  
Vol 302 (1) ◽  
pp. R118-R125 ◽  
Author(s):  
Naoya Kitao ◽  
Masaaki Hashimoto

Brown adipose tissue (BAT) is thought to play a significant physiological role during arousal when body temperature rises from the extremely low body temperature that occurs during hibernation. The dominant pathway of BAT thermogenesis occurs through the β3-adrenergic receptor. In this study, we investigated the role of the β3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vitro and in vivo. Syrian hamsters in the hibernation group contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group. Although the ability of the β3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between the hibernation and warm-acclimated groups, its maximum ratio over the basal value at 12°C in the hibernation group was significantly larger than that in the warm-acclimated group. Forskolin stimulation at 12°C produced equivalent BAT responses in these two groups. In vivo thermogenesis was assessed with the arousal time determined by the time course of BAT temperature or heart rate. Stimulation of BAT by CL316,243 significantly shortened the time of arousal from hibernation compared with that induced by vehicle alone, and it also induced arousal in deep hibernating animals. The β3-antagonist SR59230A inhibited arousal from hibernation either in part or completely. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective β3-receptor mechanism at lower temperatures.


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 ◽  
...  

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.


2002 ◽  
Vol 174 (3) ◽  
pp. 427-433 ◽  
Author(s):  
H Budge ◽  
A Mostyn ◽  
V Wilson ◽  
A Khong ◽  
AM Walker ◽  
...  

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.


2012 ◽  
Vol 216 (2) ◽  
pp. 157-168 ◽  
Author(s):  
Edward T Wargent ◽  
Jacqueline F O'Dowd ◽  
Mohamed S Zaibi ◽  
Dan Gao ◽  
Chen Bing ◽  
...  

Previous studies by Tisdaleet al. have reported that zinc-α2-glycoprotein (ZAG (AZGP1)) reduces body fat content and improves glucose homeostasis and the plasma lipid profile in Aston (ob/ob) mice. It has been suggested that this might be mediated via agonism of β3- and possibly β2-adrenoceptors. We compared the effects of dosing recombinant human ZAG (100 μg, i.v.) and BRL35135 (0.5 mg/kg, i.p.), which is in rodents a 20-fold selective β3- relative to β2-adrenoceptor agonist, given once daily for 10 days to male C57Bl/6Lepob/Lepobmice. ZAG, but not BRL35135, reduced food intake. BRL35135, but not ZAG, increased energy expenditure acutely and after sub-chronic administration. Only BRL35135 increased plasma concentrations of glycerol and non-esterified fatty acid. Sub-chronic treatment with both ZAG and BRL35135 reduced fasting blood glucose and improved glucose tolerance, but the plasma insulin concentration 30 min after administration of glucose was lowered only by BRL35135. Both ZAG and BRL35135 reduced β1-adrenoceptor mRNA levels in white adipose tissue, but only BRL35135 reduced β2-adrenoceptor mRNA. Both ZAG and BRL35135 reduced β1-adrenoceptor mRNA levels in brown adipose tissue, but neither influenced β2-adrenoceptor mRNA, and only BRL35135 increased β3-adrenoceptor and uncoupling protein-1 (UCP1) mRNA levels in brown adipose tissue. Thus, ZAG and BRL35135 had similar effects on glycaemic control and shared some effects on β-adrenoceptor gene expression in adipose tissue, but ZAG did not display the thermogenic effects of the β-adrenoceptor agonist, nor did it increase β3-adrenoceptor orUCP1gene expression in brown adipose tissue. ZAG does not behave as a typical β3/2-adrenoceptor agonist.


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