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 ◽  
...  

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.

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.


2001 ◽  
Vol 29 (2) ◽  
pp. 80-85 ◽  
Author(s):  
T. Stephenson ◽  
H. Budge ◽  
A. Mostyn ◽  
S. Pearce ◽  
R. Webb ◽  
...  

During late gestation, the maturation of fetal adipose tissue is geared towards the synthesis of high levels of uncoupling protein 1 (UCP1), which is unique to brown adipose tissue. At birth, rapid activation of UCP1 ensures a large increase in heat production. These adaptations are nutritionally sensitive, and may be mediated in part by rapid changes in prolactin and leptin secretion after birth. Restriction of maternal nutrition reduces adipose tissue deposition, with no effect on UCP1. Increased maternal food intake results in increases in levels of UCP1 and the short form of the prolactin receptor, but in a decrease in adipose tissue content per kg of fetus. The ontogeny of the long and short forms of the prolactin receptor follows that of UCP1, to peak at birth. Then, during postnatal life, UCP1 disappears in parallel with the loss of prolactin receptors. Treatment of neonatal lambs with prolactin increases body temperature and the thermogenic potential of brown adipose tissue. In contrast, acute leptin treatment results in maintenance of colonic temperature, but chronic leptin treatment accelerates UCP1 loss. Increasing our understanding of the interaction between prolactin and leptin during perinatal development may enable the establishment of strategies aimed at maximizing adipose tissue development in order to promote metabolic adaptation to the extra-uterine environment.


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.


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.


1985 ◽  
Vol 53 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Julia M. Duerden ◽  
C. J. Bates

1. An increase in 1iver:body-weight and in hepatic triacylglycerol content, together with changes in the fatty acid profiles of hepatic phospholipids, were observed as a result of moderate riboflavin deficiency in sucking rat pups. Oxygen consumption by hepatic mitochondria, with palmitoyl L-carnitine as substrate, was not significantly impaired.2. Mitochondria from interscapular brown adipose tissue, however, showed a marked impairment of O2 Consumption, with palmitoyl L-carnitine as substrate, in the riboflavin-deficient pups. This impairment was also apparent after uncoupling with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, but was not consistently observed after the addition of GDP to suppress uncoupled oxidation. It was much less evident, and did not reach statistical significance, for the mitochondria of brown adipose tissue of the corresponding deficient dams.3. Binding of 3H-labe11ed GDP by brown adipose tissue mitochondria was unaffected by riboflavin deficiency in the pups, suggesting that the effect on O2 consumption is more likely to be due to impaired integrity of the mitochondrial respiratory chain, than to impairment of the specific capacity for uncoupling of respiration which is characteristic of brown adipose tissue mitochondria. Total cytochrome c oxidase (EC 1.9.3.1) activity of the brown adipose tissue of riboflavin-deficient pups was not significantly reduced.4. A small but significant impairment was observed in the stimulation ofwhole-body O2consumption by injected noradrenaline in the riboflavin-deficient pups, suggesting that the impairment of brown adipose tissue mitochondrial function may be accompanied by impaired physiological capacity in vivo.


1989 ◽  
Vol 259 (2) ◽  
pp. 341-346 ◽  
Author(s):  
M J Obregón ◽  
A Jacobsson ◽  
T Kirchgessner ◽  
M C Schotz ◽  
B Cannon ◽  
...  

In order to investigate the postnatal recruitment process, gene expression in the brown adipose tissue of rat pups was followed during the first 20 h of life. In normal pups, the level of mRNA coding for the uncoupling protein thermogenin increased markedly but gradually within the first 24 h. Lipoprotein lipase and actin mRNA levels were relatively low and remained constant. In pups exposed to thermoneutral temperature (35 degrees C) for the first 12 h after birth, no increase in thermogenin mRNA or lipoprotein lipase mRNA was observed, whereas in pups exposed to 28 degrees C a clear increase in both thermogenin and lipoprotein lipase mRNA levels was found. Actin mRNA levels were not affected by the environmental temperature under these circumstances. It was concluded that the postnatal recruitment in brown adipose tissue is a consequence of the cold stress experienced by the newborn pups. Thus, postnatal recruitment is not ontogenically predetermined.


1988 ◽  
Vol 254 (1) ◽  
pp. R11-R16 ◽  
Author(s):  
P. Trayhurn ◽  
G. Jennings

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.


1986 ◽  
Vol 71 (3) ◽  
pp. 291-297 ◽  
Author(s):  
M. E. J. Lean ◽  
W. P. T. James ◽  
G. Jennings ◽  
P. Trayhurn

1. A solid-phase radioimmunoassay is described for the estimation of the uncoupling protein content of human brown adipose tissue mitochondria, as an index of thermogenic capacity. 2. The concentration of inner mitochondrial membrane uncoupling protein was measured in brown adipose tissue samples from 48 individuals who died suddenly. 3. The uncoupling protein content of axillary adipose tissue was greater than that of perirenal adipose tissue. 4. Variations in brown adipose tissue uncoupling protein content, which would be consistent with changing thermogenic requirements and capacity, were observed in different groups of subjects. Significantly lower concentrations were found in adults and in pre-term and stillborn infants than in older infants and children.


2003 ◽  
Vol 176 (1) ◽  
pp. 31-38 ◽  
Author(s):  
N Petrovic ◽  
G Cvijic ◽  
V Davidovic

The activity of the antioxidant enzymes copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity, uncoupling protein-1 (UCP1) content, catecholamine degrading enzyme monoamine oxidase (MAO) activity and malonyl dialdehyde (MDA) concentration were studied in rat interscapular brown adipose tIssue (IBAT). Rats were treated with either thyroxine (T4) or tri-iodothyronine (T3) for five days and then exposed to cold (4 degrees C, 24 h) or housed at room temperature (22 degrees C). Under basal conditions, T3 treatment significantly increased UCP1 content and MnSOD activity whereas CuZnSOD, CAT and MAO activities were significantly decreased. Thyroxine treatment significantly decreased IBAT CAT activity while MDA levels markedly increased. Cold exposure induced a significant augmentation of UCP1 content and MnSOD and mGPDH activities only in animals that were rendered hyperthyroid by T4 treatment. In T3-treated animals acutely exposed to cold stress, MDA concentration, an indicator of lipid peroxidation, was significantly higher compared with that of T3-treated animals housed at room temperature. However, in T4-treated animals, MDA concentrations were markedly lower. These results show that T4 and T3 differently affect IBAT parameters studied not only under basal but also under cold-stimulated conditions.


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