scholarly journals Inhibition of Uncoupling Protein Expression during Lactation: Role of Leptin

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 830-838 ◽  
Author(s):  
Xiao Qiu Xiao ◽  
Kevin L. Grove ◽  
Bernadette E. Grayson ◽  
M. Susan Smith
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Atp Synthesis ◽  
Negative Energy ◽  
Down Regulation ◽  
Serum Free Fatty Acid ◽  
Serum Leptin ◽  
Brown Adipose

Abstract Uncoupling proteins (UCPs) are mitochondrial proteins that play a role in regulation of energy expenditure by uncoupling respiration from ATP synthesis. Lactation is a physiological condition characterized by negative energy balance due to the loss of energy sources to the production of milk. The objective of the current study was to investigate whether UCP mRNA and protein expressions were altered during lactation compared with those after 48 h of fasting. Lactation significantly reduced serum leptin levels, and removal of pups for 48 h increased serum leptin to higher levels than those observed in control rats. Compared with control rats, mRNA expression of UCP1 and UCP3 in brown adipose tissue (BAT) was dramatically reduced during lactation and fasting. The reduction in mRNAs was reflected by a lowered UCP1 protein level, and to some extent, UCP3 protein. Treatment of lactating rats with exogenous leptin (3 mg/kg) or removal of pups for 48 h completely reversed the down-regulation of UCP1 and UCP3 mRNA expression in BAT, and pup removal led to a recovery of protein expression. In contrast to BAT, UCP3 expression in skeletal muscle was increased in fasted rats and decreased during lactation. Similar changes were observed in serum free fatty acid levels. These changes are consistent with the idea that the utilization of free fatty acids as a fuel source is spared during lactation. As in BAT, leptin treatment and removal of pups were able to restore changes in mRNA expression of UCP3 in skeletal muscle during lactation. The present results suggest that the inhibition of leptin secretion during lactation is involved in the down-regulation of UCP expression in BAT and skeletal muscle, which, in turn, is responsible for the decrease in metabolic fuel oxidation and thermogenesis.

Differential regulation of expression of genes encoding uncoupling proteins 2 and 3 in brown adipose tissue during lactation in mice

2001 ◽  
Vol 355 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Neus PEDRAZA ◽  
Gemma SOLANES ◽  
Roser IGLESIAS ◽  
Manuel VÁZQUEZ ◽  
Marta GIRALT ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Down Regulation ◽  
Gene Encoding ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Ucp2 Mrna

Thermogenic activity in brown adipose tissue (BAT) decreases during lactation; the down-regulation of the gene encoding uncoupling protein 1 (UCP1) is involved in this process. Our studies show that UCP2 mRNA expression does not change during the breeding cycle in mice. In contrast, UCP3 mRNA is down-regulated in lactation but it recovers after weaning, in parallel with UCP1 mRNA. This leads to a decrease in the content of UCP3 in BAT mitochondria during lactation. Lowering the energy-sparing necessities of lactating dams by decreasing litter size or feeding with a high-fat diet prevented the down-regulation of UCP1 mRNA and UCP3 mRNA. In most cases this resulted in a less marked decrease in UCP1 and UCP3 protein in BAT mitochondria owing to lactation. Fasting for 24h caused a different response in UCP1 and UCP3 mRNA expression: it decreased UCP1 mRNA levels but had no effect on UCP3 mRNA abundance in virgin mice; it even increased UCP3 mRNA expression in lactating dams. These changes did not lead to modifications in UCP1 or UCP3 protein abundance. Whereas acute treatment with peroxisome-proliferator-activated receptor (PPAR)α and PPARγ agonists increased UCP1 mRNA levels only in lactating dams, UCP3 mRNA expression was induced by both kinds of PPAR activator in lactating dams and by PPARα agonists in virgin mice. It is concluded that modifications of UCP2 mRNA levels are not part of the physiological adaptations taking place in BAT during lactation. In contrast, the down-regulation of UCP3 mRNA expression and mitochondrial UCP3 content is consistent with a role for the gene encoding UCP3 in the decrease in metabolic fuel oxidation and thermogenesis in BAT during lactation.

scholarly journals Effect of β1- and β2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans

2003 ◽  
Vol 285 (4) ◽  
pp. E775-E782 ◽  
Author(s):  
Joris Hoeks ◽  
Marleen A. van Baak ◽  
Matthijs K. C. Hesselink ◽  
Gabby B. Hul ◽  
Hubert Vidal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Expenditure ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Plasma Free Fatty Acid ◽  
Substrate Oxidation ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Before And After ◽  
Plasma Ffa

In humans, β-adrenergic stimulation increases energy and fat metabolism. In the case of β1-adrenergic stimulation, it is fueled by an increased lipolysis. We examined the effect of β2-adrenergic stimulation, with and without a blocker of lipolysis, on thermogenesis and substrate oxidation. Furthermore, the effect of β1-and β2-adrenergic stimulation on uncoupling protein 3 (UCP3) mRNA expression was studied. Nine lean males received a 3-h infusion of dobutamine (DOB, β1) or salbutamol (SAL, β2). Also, we combined SAL with acipimox to block lipolysis (SAL+ACI). Energy and substrate metabolism were measured continuously, blood was sampled every 30 min, and muscle biopsies were taken before and after infusion. Energy expenditure significantly increased ∼13% in all conditions. Fat oxidation increased 47 ± 7% in the DOB group and 19 ± 7% in the SAL group but remained unchanged in the SAL+ACI condition. Glucose oxidation decreased 40 ± 9% upon DOB, remained unchanged during SAL, and increased 27 ± 11% upon SAL+ACI. Plasma free fatty acid (FFA) levels were increased by SAL (57 ± 11%) and DOB (47 ± 16%), whereas SAL+ACI caused about fourfold lower FFA levels compared with basal levels. No change in UCP3 was found after DOB or SAL, whereas SAL+ACI downregulated skeletal muscle UCP3 mRNA levels 38 ± 13%. In conclusion, β2-adrenergic stimulation directly increased energy expenditure independently of plasma FFA levels. Furthermore, this is the first study to demonstrate a downregulation of skeletal muscle UCP3 mRNA expression after the lowering of plasma FFA concentrations in humans, despite an increase in energy expenditure upon β2-adrenergic stimulation.

Artifactual uncoupling by uncoupling protein 3 in yeast mitochondria at the concentrations found in mouse and rat skeletal-muscle mitochondria

2001 ◽  
Vol 361 (1) ◽  
pp. 49-56 ◽  
Author(s):  
James A. HARPER ◽  
Jeff A. STUART ◽  
Mika B. JEKABSONS ◽  
Damien ROUSSEL ◽  
Kevin M. BRINDLE ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Yeast Mitochondria ◽  
Rat Skeletal Muscle ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Uncoupling Protein 3 ◽  
Brown Adipose

Western blots detected uncoupling protein 3 (UCP3) in skeletal-muscle mitochondria from wild-type but not UCP3 knock-out mice. Calibration with purified recombinant UCP3 showed that mouse and rat skeletal muscle contained 0.14μg of UCP3/mg of mitochondrial protein. This very low UCP3 content is 200–700-fold less than the concentration of UCP1 in brown-adipose-tissue mitochondria from warm-adapted hamster (24–84μg of UCP1/mg of mitochondrial protein). UCP3 was present in brown-adipose-tissue mitochondria from warm-adapted rats but was undetectable in rat heart mitochondria. We expressed human UCP3 in yeast mitochondria at levels similar to, double and 7-fold those found in rodent skeletal-muscle mitochondria. Yeast mitochondria containing UCP3 were more uncoupled than empty-vector controls, particularly at concentrations that were 7-fold physiological. However, uncoupling by UCP3 was not stimulated by the known activators palmitate and superoxide; neither were they inhibited by GDP, suggesting that the observed uncoupling was a property of non-native protein. As a control, UCP1 was expressed in yeast mitochondria at similar concentrations to that of UCP3 and at up to 50% of the physiological level of UCP1. Low levels of UCP1 gave palmitate-dependent and GDP-sensitive proton conductance but higher levels of UCP1 caused an additional GDP-insensitive uncoupling artifact. We conclude that the uncoupling of yeast mitochondria by high levels of UCP3 expression is entirely an artifact and provides no evidence for any native uncoupling activity of the protein.

Tea catechins enhance the mRNA expression of uncoupling protein 1 in rat brown adipose tissue

2008 ◽  
Vol 19 (12) ◽  
pp. 840-847 ◽  
Author(s):  
Sachiko Nomura ◽  
Takashi Ichinose ◽  
Manabu Jinde ◽  
Yu Kawashima ◽  
Kaoru Tachiyashiki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Tea Catechins ◽  
Brown Adipose

Central stimulatory effect of leptin on T3production is mediated by brown adipose tissue type II deiodinase

2002 ◽  
Vol 283 (5) ◽  
pp. E980-E987 ◽  
Author(s):  
Philippe Cettour-Rose ◽  
Albert G. Burger ◽  
Christoph A. Meier ◽  
Theo J. Visser ◽  
Françoise Rohner-Jeanrenaud
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Tissue Type ◽  
Type I ◽  
Type Ii ◽  
Brown Adipose ◽  
Small Doses ◽  
Food Consumed

To assess whether intracerebroventricular leptin administration affects monodeiodinase type II (D2) activity in the tissues where it is expressed [cerebral cortex, hypothalamus, pituitary, and brown adipose tissue (BAT)], hepatic monodeiodinase type I (D1) activity was inhibited with propylthiouracil (PTU), and small doses of thyroxine (T4; 0.6 nmol · 100 g body wt−1 · day−1) were supplemented to compensate for the PTU-induced hypothyroidism. Two groups of rats were infused with leptin for 6 days, one of them being additionally treated with reverse triiodothyronine (rT3), an inhibitor of D2. Control rats were infused with vehicle and pair-fed the amount of food consumed by leptin-infused animals. Central leptin administration produced marked increases in D2 mRNA expression and activity in BAT, changes that were likely responsible for increased plasma T3 and decreased plasma T4 levels. Indeed, plasma T3 and T4 concentrations were unaltered by central leptin administration in the presence of rT3. The additional observation of a leptin-induced increased mRNA expression of BAT uncoupling protein-1 suggested that the effect on BAT D2 may be mediated by the sympathetic nervous system.

The Regulation of Telomere Binding Proteins on Telomerase during Differentiation of ATRA Responsive and Resistant NB4 Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3390-3390
Author(s):  
He Huang ◽  
Jie Sun ◽  
Yuan Yuan Zhu ◽  
Jian Ping Lan ◽  
Xiao Yu Lai
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Peak Level ◽  
Telomerase Activity ◽  
Expression Level ◽  
Htert Mrna ◽  
Down Regulation ◽  
Nb4 Cells ◽  
Significant Change ◽  
Htert Mrna Expression

Abstract It has been reported that the down-regulation of telomerase activity associated with maturation of APL cells is not mechanistically linked to cell maturation, and requires only a RAR, but not a RXR-dependent pathway. However, it is not clear whether and how telomeric proteins respond to the retinoid treatment. Using maturation-sensitive and resistant APL cell lines NB4, NB4-R1 and NB4-R2 cells, we analyzed a panel of telomeric proteins using western blotting analyses in addition to temporal profile of corresponding mRNA during the course of retinoid-induced differentiation. Our analyses show hTERTmRNA expression decreased rapidly during differentiation of NB4 and NB4-R1 cells, telomerase activity also declined. But in NB4-R2 cells, hTERT mRNA was initially decreased to 38.2% on day1 (P<0.05) and then increased to 80.0% on day 3 (P<0.05). Telomerase activity remained unchanged overtime (P>0.05), which may be caused by the increasing of hTERT mRNA expression during its later period of differentiation. TRF1 mRNA and protein expression have no significant change during differentiation in NB4 and NB4-R1 cells but has a small increase in NB4-R2 cells. The TRF1 mRNA expression level has no significant change during differentiation of NB4 and NB4-R1 cell line cells. However, it was increased to 235% on day 2 (P<0.05) and remains at this level until day 3 during the differentiation of NB4-R2 cells. TRF1 protein expression level also remains stable during differentiation of NB4 and NB4-R1 cells, but has a little increase in NB4-R2 cells. This indicates TRF1 has different regulation in RARα dependent or RXRα dependent pathways. Pinx1 mRNA expression decreased during the differentiation of NB4 and NB4-R1. But during the differentiation of NB4-R2, Pinx1mRNA expressions level was initially decreased to 34.3% (P<0.05) on day 1 then increased to 64.5% (P<0.05 compared to day1) on day2. The change of Pinx1 mRNA expression and hTERT mRNA expression in NB4(r=0.902, P=0.036), NB4-R1(r=1.00, P<0.001), and NB4-R2(r=0.880, P=0.049) cells are positive correlated. Pinx1 is the only telomere binding protein that can bind to hTERT directly, it might be responsible for the different regulation of telomerase activity through RARα dependent or RXRα dependent pathways. During NB4 cell differentiation, TANK1 mRNA expression decreased gradually to 31.6% (P<0.05) on day1, and remained this level until day3. In NB4-R1 cells, TANK1 mRNA expression increased initially to 197% at 12h(P<0.05), and then decreased gradually to 111% (P<0.05) on day 3. During the differentiation of NB4-R2 cells, TANK1 mRNA expression was initially increased to 204% at 12h(P<0.01), and then decreased gradually to 96.9% on day3 (P<0.01). Its protein expression initially increased and reached a peak level at day 1 and then decreased in the later period of differentiation of all three NB4 cells. Both TANK1 mRNA expression and its protein expression were down-regulated at the later period of differentiation in all three NB4 cells. It seems that TANK1 may act as a positive regulator on telomerase activity during differentiation. TANK2 mRNA expression remained no change during differentiation of three NB4 cells. As results show, Pinx1 and TANK1 may interfere in the regulation of telomerase. The decrease of TANK1 may be the cause of the down-regulation of telomerase activity. Further studies will focus on the mechanism of their regulation on telomerase.

Adaptive characters of energy metabolism, thermogenesis and body mass in Eothenomys miletus during cold exposure and rewarming

2012 ◽  
Vol 62 (3) ◽  
pp. 263-276 ◽  
Author(s):  
Zhu Wan-long ◽  
Cai Jin-hong ◽  
Lian Xiao ◽  
Wang Zheng-kun
Keyword(s):  
Ambient Temperature ◽  
Energy Intake ◽  
Body Mass ◽  
Uncoupling Protein ◽  
Resting Metabolic Rate ◽  
Serum Leptin ◽  
Body Mass Regulation ◽  
Brown Adipose ◽  
And Behavior ◽  
Eothenomys Miletus

Environmental cues play important roles in the regulation of an animal’s physiology and behavior. The purpose of the present study was to test the hypothesis that ambient temperature was a cue to induce adjustments in body mass, energy intake and thermogenic capacity, associated with changes in serum leptin levels inEothenomys miletus. We found thatE. miletusincreased resting metabolic rate (RMR) and energy intake and decreased body mass when exposed to cold while it showed a significant increase in body mass after rewarming. The increase in body mass after rewarming was associated with the higher energy intake compared with the control. Uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT) increased in the cold and reversed after rewarming. Serum leptin levels decreased in the cold while increased after rewarming, associated with the opposite changes in energy intake. Further, serum leptin levels were positively correlated with body mass and body fat mass. Together, these data supported our hypothesis that ambient temperature was a cue to induce changes in body mass and metabolism. Serum leptin, as a starvation signal in the cold and satiety signal in rewarming, was involved in the processes of thermogenesis and body mass regulation inE. miletus.

Impaired response of UCP family to cold exposure in diabetic (db/db) mice

2000 ◽  
Vol 279 (4) ◽  
pp. R1305-R1309 ◽  
Author(s):  
Takayuki Masaki ◽  
Hironobu Yoshimatsu ◽  
Seiichi Chiba ◽  
Toshiie Sakata
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Lipolytic Activity ◽  
Uncoupling Protein ◽  
Leptin Resistance ◽  
Obese Mice ◽  
Serum Free Fatty Acid ◽  
Serum Free ◽  
Ucp2 Expression ◽  
Brown Adipose

Impaired activity of the uncoupling protein (UCP) family has been proposed to promote obesity development. The present study examined differences in UCP responses to cold exposure between leptin-resistance obese ( db/db) mice and their lean (C57Ksj) littermates. Basal UCP1 and UCP3 mRNA expression in brown adipose tissue was lower in obese mice compared with lean mice, but UCP2 expression in white adipose tissue (WAT) was higher. Basal skeletal muscle UCP3 did not change remarkably. The UCP family mRNAs, which were upregulated 12 and 24 h after cold exposure (4°C), were returned to prior levels 12 h after rewarming exposure (21°C) in lean mice. The accelerating effects of cold exposure on the UCP family were impaired in db/db obese mice. Together with these changes, WAT lipoprotein lipase mRNA was downregulated, and the concentration of serum free fatty acid was increased in response to cold exposure in the lean mice but not in db/db obese littermates. The impaired function of the UCP family and diminished lipolysis in response to cold exposure indicate that the reduced lipolytic activity may contribute to the inactivation of the UCP family in db/db obese mice.

scholarly journals Maternal consumption of high-prebiotic fibre or -protein diets during pregnancy and lactation differentially influences satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring in rats

2010 ◽  
Vol 105 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Alannah D. Maurer ◽  
Raylene A. Reimer
Keyword(s):  
Lipid Metabolism ◽  
Mrna Expression ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Maternal Diet ◽  
Glucose And Lipid Metabolism ◽  
The Metabolic Syndrome ◽  
Expression Of Genes ◽  
Brown Adipose ◽  
Pregnancy And Lactation

Risk of developing the metabolic syndrome may be influenced by nutritional environment early in life. We examined the effects of high-fibre (HF) and high-protein (HP) diets consumed during pregnancy and lactation on satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring. Wistar dams were fed a control (C), HF or HP diets during pregnancy and lactation. At parturition, litters were culled to ten pups. At 21 d, all pups were weaned onto C diet. At 7, 14, 21, 28 and 35 d after birth, blood was analysed for satiety hormones and tissues for mRNA expression in offspring. No differences were observed in litter size or birth weight. At 21 d, offspring of HF dams had greater adjusted intestinal mass and lower liver weight than those of C but not of HP dams. Plasma glucose at 28 d and amylin at 7, 14 and 28 d were lower in HF v. C and HP offspring. Glucagon-like peptide-1 was higher in HP offspring than in HF offspring at 7 d but was higher in HF v. C offspring at 21 d. Offspring of HF dams had higher glucose transporter (GLUT2 and Na+-dependent glucose/galactose transporter) mRNA expression at 21 d v. C and HP offspring. In brown adipose tissue, HF and HP up-regulated uncoupling protein-1 and PPAR-γ coactivator. HP was associated with increased resistin and IL-6 mRNA expression. The present study demonstrates that maternal diet composition differentially regulates circulating satiety hormones and genes involved in glucose transport and energy metabolism in offspring. These early changes could have long-term consequences for obesity risk.

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