Brown adipose tissue and liver development during early postnatal life in hand-reared and ewe-reared lambs

1996 ◽  
Vol 8 (1) ◽  
pp. 137 ◽  
Author(s):  
CJ Darby ◽  
L Clarke ◽  
MA Lomax ◽  
ME Symonds
Keyword(s):  
Growth Rate ◽  
Adipose Tissue ◽  
Ambient Temperature ◽  
Lipid Content ◽  
Uncoupling Protein ◽  
Plasma Concentrations ◽  
Type I ◽  
Tissue Lipid ◽  
Perirenal Adipose Tissue ◽  
Brown Adipose

This study examined the effects of modest changes in ambient temperature in hand-reared lambs (experiment one) and in ewe-reared lambs (experiment two). Lambs were killed at either 8 or 31 days of age and perirenal adipose tissue was identified as being brown adipose tissue (BAT) from measurements of thermogenic activity (i.e. GDP binding to uncoupling protein in isolated mitochondria) or thermogenic capacity (i.e. detection of uncoupling protein by immunoblotting). In addition, type I and II iodothyronine 5' monodeiodonase (5'MDI) activities were assayed in perirenal adipose tissue, plus type I 5'MDI activity in liver. Plasma samples were also taken for measurements of glucose, lactate, insulin, triiodothyronine (T3) and thyroxine (T4) concentrations. In experiment one, lambs were hand-reared at either warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperatures. Mean growth rate over the first 8 days of life in CR lambs was 88 g/day and increased to 128 g/day over the first month of life. Growth rate in WR lambs was constant at 141 g/day. Thermogenic activity of BAT was significantly higher in CR than WR lambs, but total weight and tissue lipid content of perirenal adipose tissue were significantly lower in the CR group. In both WR and CR lambs, the thermogenic activity of BAT fell by an average of 71% between 8 and 31 days. At 31 days of age, uncoupling protein in mitochondria could be detected only by immunoblotting in adipose tissue sampled from CR lambs. There was no effect of ambient temperature on type I or type II 5'MDI activity in BAT or liver; it decreased in adipose but not liver tissue between 8 and 31 days of age. The plasma concentrations of glucose, insulin and T3 tended to decline with age in CR but not in WR lambs. In ewe-reared lambs perirenal adipose tissue weight and tissue lipid content more than doubled between 8 and 31 days of age, but the level of GDP binding decreased from 85 to 5 pmol/mg mitochondrial protein over this period. Liver weight increased by 55% between 8 and 31 days of age, but hepatic 5'MDI activity remained unchanged. The plasma concentrations of T3, T4 and lactate, but not glucose or insulin, increased between 8 and 31 days of age. It is concluded that hand-rearing lambs at a cool ambient temperature significantly delays postnatal development, to the extent that BAT characteristics are retained. Ewe-rearing lambs enhances the rate at which BAT adopts the characteristics of white adipose tissue, and it prevents the postnatal decline in plasma concentrations of thyroid hormones.

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.

scholarly journals Iodothyronine 5′-deiodinase activity as an early event of prenatal brown-fat differentiation in bovine development

1989 ◽  
Vol 259 (2) ◽  
pp. 555-559 ◽  
Author(s):  
M Giralt ◽  
L Casteilla ◽  
O Viñas ◽  
T Mampel ◽  
R Iglesias ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Early Event ◽  
Type I ◽  
Fetal Life ◽  
Reverse T3 ◽  
Deiodinase Activity ◽  
Brown Adipose

Iodothyronine 5'-deiodinase activity appears to be a type I enzyme in bovine brown adipose tissue, on the basis of its high Km for 3,3',5'-tri-iodothyronine (‘reverse T3’) (in the micromolar range) and sensitivity to propylthiouracil inhibition. This enzyme activity is already detectable in perirenal adipose tissue of bovine fetuses in the second month of gestation, reaches peak values around the seventh month of fetal life, declines before birth, becomes lower after parturition and finally undetectable in the adult cow. Iodothyronine 5'-deiodinase activity is present in the pericardic, peritoneal and intermuscular adipose depots of the neonatal calf, but it is always undetectable in the subcutaneous adipose tissue. It is concluded that iodothyronine 5'-deiodinase is a specific feature of brown fat in the bovine species that is not shared by white adipose tissue. white adipose tissue. Peak values of 5'-deiodinating activity appear as an early event in the prenatal differentiation programme of bovine brown-fat cells as they occur when uncoupling-protein-gene expression first starts.

Nicotine infusion alters leptin and uncoupling protein 1 mRNA expression in adipose tissues of rats

2001 ◽  
Vol 280 (6) ◽  
pp. E867-E876 ◽  
Author(s):  
Keiko Arai ◽  
Kyongsong Kim ◽  
Katsumi Kaneko ◽  
Mitsue Iketani ◽  
Asuka Otagiri ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Wistar Rats ◽  
Uncoupling Protein ◽  
Plasma Concentrations ◽  
Uncoupling Protein 1 ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Male Wistar Rats ◽  
Infusion Period

We attempted to clarify whether leptin and uncoupling protein 1 (UCP1) are involved in the action of nicotine on the energy balance. Male Wistar rats were infused subcutaneously with nicotine (12 mg · kg−1 · day−1) for 4 or 14 days. At the end of the 4-day period, the plasma concentrations of leptin of the nicotine-treated and pair-fed rats were lower than those of the freely fed rats, although the levels of leptin mRNA expression in various white adipose tissues did not differ among the three groups. At the end of the 14-day nicotine infusion period, plasma concentrations of leptin were higher, and leptin mRNA expression in the omentum and epididymal and retroperitoneal adipose tissues was stronger in the nicotine-treated rats than in the pair-fed and freely fed rats. UCP1 mRNA expression in the brown adipose tissue of nicotine-treated was stronger than that of the pair-fed rats. These results suggest that continuous nicotine infusion differentially affects the synthesis and secretion of leptin according to the duration of infusion and stimulates UCP1 mRNA expression, probably in a manner independent of leptin.

scholarly journals Influence of maternal dexamethasone administration on thermoregulation in lambs delivered by caesarean section

1998 ◽  
Vol 156 (2) ◽  
pp. 307-314 ◽  
Author(s):  
I Clarke ◽  
L Heasman ◽  
ME Symonds
Keyword(s):  
Adipose Tissue ◽  
Caesarean Section ◽  
Thyroid Hormones ◽  
Ambient Temperature ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Premature Delivery ◽  
Dexamethasone Treatment ◽  
Brown Adipose ◽  
Colonic Temperature

We have previously shown that lambs delivered by caesarean section 1 week prematurely become hypothermic due to reduced brown adipose tissue function in conjunction with low plasma concentrations of cortisol and thyroid hormones. The present study therefore aimed to determine whether maternal dexamethasone (a synthetic corticosteroid) administration could improve thermoregulation in premature lambs to the extent that they become similar to term lambs. Lambs were either delivered by caesarean section into a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature at 140 days of gestation, 2 days after maternal dexamethasone treatment, or at 146 days for controls. During the first 30 min of life the decline in colonic temperature was greater in dexamethasone treated lambs compared with controls delivered into the same ambient temperature. All lambs then restored colonic temperature although this adaptation took longest in dexamethasone treated lambs CD but these subsequently attained highest plateau colonic temperatures. Oxygen consumption, breathing frequency and plasma free fatty acid concentrations were highest in dexamethasone treated lambs CD. There were no differences in plasma thyroid hormones between groups, but cortisol concentrations were lower in dexamethasone treated lambs irrespective of delivery temperature. Analysis of brown adipose tissue samples at 6 h of life demonstrated that dexamethasone treated lambs WD had more uncoupling protein and, in both dexamethasone treated and control lambs, uncoupling protein content was higher in lambs CD compared with those WD. An effect of ambient temperature on thermogenic activity was only observed in the dexamethasone treated group. It is concluded that maternal dexamethasone treatment can significantly improve thermoregulation after birth following premature delivery by caesarean section. As a consequence, dexamethasone treated lambs delivered 1 week prematurely do not remain hypothermic and have higher or similar colonic temperatures compared with untreated lambs born 1-2 days before term.

Brown Adipose Tissue and Its Uncoupling Protein in Chronically Hypoxic Rats

1997 ◽  
Vol 93 (4) ◽  
pp. 349-354 ◽  
Author(s):  
Jacopo P. Mortola ◽  
Lina Naso
Keyword(s):  
Adipose Tissue ◽  
Ambient Temperature ◽  
Brown Adipose Tissue ◽  
Body Mass ◽  
Uncoupling Protein ◽  
Total Proteins ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Adipose Tissue Mass ◽  
Old Rats

1. Hypoxia is known to decrease thermogenesis. We set out to determine whether this is accompanied by alterations in the brown adipose tissue, which is a major source of non-shivering thermogenesis. 2. Measurements were performed on 25- and 64-day-old rats, after 4 days of hypoxia (10% inspired O2), and on ∼3.5-month-old rats in hypobaric hypoxia since birth, at an ambient temperature of 25°C. 3. All hypoxic rats had higher haematocrit and lower body mass than corresponding controls. 4. In the 25-day-old rats, hypoxia had minimal and non significant effects on brown adipose tissue mass, proteins and DNA concentration. The content of the mitochondrial uncoupling protein thermogenin, evaluated by immunoblot after electrophoretic separation, relative to the cytoskeleton actin (UCP/Act), was not significantly altered. 5. In 25-day-old rats exposed for 4 days to cold (ambient temperature = 7–9°C), brown adipose tissue was hyperplastic, with increased UCP/Act; hypoxia did not appreciably alter the response to cold. 6. In the 2-month-old rats, after 4 days of hypoxia UCP/Act was reduced to about 40% of control. 7. In the 3.5-month-old rats maintained in hypoxia since birth, brown adipose tissue mass was reduced in proportion to body mass, with little effect on total proteins and DNA; UCP/Act was decreased to about 50% of control. 8. We conclude that chronic hypoxia had a minimal effect on brown adipose tissue total proteins and DNA content. However, the uncoupling protein content can be greatly reduced, depending upon age and duration of hypoxia.

scholarly journals Adipose tissue growth and development: the modulating role of ambient temperature

2021 ◽  
Vol 248 (1) ◽  
pp. R19-R28
Author(s):  
Michael E Symonds ◽  
Mark Pope ◽  
Ian Bloor ◽  
James Law ◽  
Reham Alagal ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ambient Temperature ◽  
Uncoupling Protein ◽  
Tissue Growth ◽  
Long Term Effects ◽  
Mitochondrial Uncoupling ◽  
Fat Depots ◽  
Brown Adipose ◽  
Beige Fat ◽  
And Function

Adipose tissue is usually laid down in small amounts in the foetus and is characterised as possessing small amounts of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP)1. In adults, a primary factor determining the abundance and function of UCP1 is ambient temperature. Cold exposure causes activation and the rapid generation of heat through the free flow of protons across the mitochondria with no requirement to convert ADP to ATP. In rodents, housing at an ambient temperature below thermoneutrality promotes the appearance of beige like adipocytes. These arise as discrete regions of UCP1 containing cells in white fat depots. There is increasing evidence to show that to gain credible translational results on brown and beige fat function in rodent models that they should be housed at thermoneutrality. This not only reflects the type of environment in which humans spend a majority of their time, but is in accord with the rise of global temperature caused by industrialisation and the uncontrolled burning of fossil fuels. There is now good evidence in adult humans, that stimulating brown fat can improve glucose homeostasis which can be achieved either by nutritional or pharmacological interventions. The challenge, therefore, is to establish credible developmental models in animals maintained at thermoneutrality which will elucidate the true impact of nutrition. The primary focus should fall specifically on the components of breast milk and how these modulate long term effects on brown or beige fat development and function.

scholarly journals Sex-Dependent Effects of Eicosapentaenoic Acid and UCP1 Deficiency on Hepatic Steatosis in Diet-Induced Obese Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1193-1193
Author(s):  
Kembra Albracht-Schulte ◽  
Salvador Galindo ◽  
Sarah Anjum ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
Ambient Temperature ◽  
Hepatic Steatosis ◽  
Uncoupling Protein ◽  
Expression Profiles ◽  
Mitochondrial Protein ◽  
Male And Female ◽  
Female Mice ◽  
Brown Adipose

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic triglyceride (TG) accumulation, is associated with expansion of white adipose tissue (WAT). By contrast, brown adipose tissue (BAT) may prevent obesity and NAFLD through activity of mitochondrial uncoupling protein 1 (UCP1), which is involved in energy dissipation. Previous studies in our lab have shown that eicosapentaenoic acid (EPA) ameliorates obesity and hepatic steatosis in high-fat (HF) fed male, B6 mice at thermoneutral conditions, independent of UCP1. However, it is unknown whether similar effects of EPA and UCP1 deficiency will be observed at ambient temperature, and whether they differ by sex. Thus, the goal of this project was to investigate sex-dependent mechanisms of EPA in the livers of diet-induced obese, wild type (WT) and UCP1 knockout (KO) mice housed at ambient temperature. Methods WT and UCP1 KO B6 male and female mice were fed a HF diet (45% kcal fat; WT-HF, KO-HF) or HF diet supplemented with 36g/kg EPA (WT-EPA, KO-EPA) for 14 weeks. Body weight (BW), liver histology, and specific metabolic gene expression profiles were assessed. Results Although BW significantly varied by sex, diet, and genotype, UCP1 inactivation did not significantly increase BW compared to WT in either sex. Hepatic TG accumulation varied significantly by genotype with no significant differences seen with EPA supplementation in either sex. However, markers of lipogenesis were sex-dependently impacted by genotype and diet: there were no significant differences in markers of lipogenesis (Fasn and Acaca) with UCP1 KO or EPA supplementation in males; while these markers were reduced in female KO mice compared to female WT with no response to EPA. By contrast, lipogenic markers were reduced with EPA in female WT mice. Conclusions Our findings reveal an association between NAFLD and UCP1 deficiency, indicating the importance of this mitochondrial protein in limiting hepatic lipid accumulation, particularly in females. These findings also suggest a genotypic difference in response to dietary EPA supplementation on the livers of male and female mice, with beneficial effects reported in the female WT group. Funding Sources Funded by NIH/NCCIH grant #R15AT008879-01A1.

scholarly journals Contrasts between the effects of zinc-α2-glycoprotein, a putative β3/2-adrenoceptor agonist and the β3/2-adrenoceptor agonist BRL35135 in C57Bl/6 (ob/ob) mice

2012 ◽  
Vol 216 (2) ◽  
pp. 157-168 ◽  
Author(s):  
Edward T Wargent ◽  
Jacqueline F O'Dowd ◽  
Mohamed S Zaibi ◽  
Dan Gao ◽  
Chen Bing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Fasting Blood Glucose ◽  
Plasma Concentrations ◽  
Mrna Levels ◽  
Plasma Insulin Concentration ◽  
Adrenoceptor Agonist ◽  
Brown Adipose

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.

scholarly journals Cold exposure induces dynamic, heterogeneous alterations in human brown adipose tissue lipid content

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Crystal L. Coolbaugh ◽  
Bruce M. Damon ◽  
Emily C. Bush ◽  
E. Brian Welch ◽  
Theodore F. Towse
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipid Content ◽  
Cold Exposure ◽  
Simultaneous Increase ◽  
Tissue Lipid ◽  
Resonance Imaging ◽  
Initial Value ◽  
Brown Adipose ◽  
Simultaneous Synthesis

Abstract Brown adipose tissue undergoes a dynamic, heterogeneous response to cold exposure that can include the simultaneous synthesis, uptake, and oxidation of fatty acids. The purpose of this work was to quantify these changes in brown adipose tissue lipid content (fat-signal fraction (FSF)) using fat-water magnetic resonance imaging during individualized cooling to 3 °C above a participant’s shiver threshold. Eight healthy men completed familiarization, perception-based cooling, and MRI-cooling visits. FSF maps of the supraclavicular region were acquired in thermoneutrality and during cooling (59.5 ± 6.5 min). Brown adipose tissue regions of interest were defined, and voxels were grouped into FSF decades (0–10%, 10–20%…90–100%) according to their initial value. Brown adipose tissue contained a heterogeneous morphology of lipid content. Voxels with initial FSF values of 60–100% (P < 0.05) exhibited a significant decrease in FSF while a simultaneous increase in FSF occurred in voxels with initial FSF values of 0–30% (P < 0.05). These data suggest that in healthy young men, cold exposure elicits a dynamic and heterogeneous response in brown adipose tissue, with areas initially rich with lipid undergoing net lipid loss and areas of low initial lipid undergoing a net lipid accumulation.

Characterization and postnatal development of 5'-deiodinase activity in goat perirenal fat

1994 ◽  
Vol 267 (1) ◽  
pp. R144-R149
Author(s):  
F. Nicol ◽  
H. Lefranc ◽  
J. R. Arthur ◽  
P. Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Kinetic Studies ◽  
Postnatal Life ◽  
Type I ◽  
Type Ii ◽  
Perirenal Adipose Tissue ◽  
Gold Thioglucose ◽  
Deiodinase Activity ◽  
Age Related ◽  
Brown Adipose

The capacity to generate the active thyroid hormone 3,3',5-triiodothyronine (T3) from thyroxine (T4) has been assessed in the major adipose tissue depot (perirenal) of newborn goats through measurements of iodothyronine 5'-deiodinase activity. High activity of the enzyme was found in the perirenal adipose tissue. Developmental studies demonstrated that there was a rise, then a fall, in iodothyronine 5'-deiodinase activity (per milligram of protein) over the first week of postnatal life, with a further decline between the second and third weeks. At 3 wk of age, the activity per gram of tissue was only 2% of that of the newborn; however, because of age-related increases in the lipid content of the perirenal adipose tissue, the activity per cell (per microgram of DNA) at 3 wk of age was approximately 10% of the activity in the newborn. Kinetic studies and inhibition characteristics with propylthiouracil, gold thioglucose, and T4 indicated that the iodothyronine 5'-deiodinase in goat perirenal adipose tissue is of the type I form; there was no evidence for the type II enzyme. Affinity labeling of the iodothyronine 5'-deiodinase with bromoacetyl-rT3 or bromoacetyl-T4 was consistent with this view. In contrast to goats, only the type II enzyme is evident in rats and mice. It is concluded that the perirenal (brown) adipose tissue is likely to be a significant source of T3 for other tissues in newborn goats and that there are major species variations in the form of iodothyronine 5'-deiodinase present in brown fat, with the goat exclusively exhibiting type I.

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