scholarly journals Developmental regulation of the lung in preparation for life after birth: hormonal and nutritional manipulation of local glucocorticoid action and uncoupling protein–2

2006 ◽  
Vol 188 (3) ◽  
pp. 375-386 ◽  
Author(s):  
M G Gnanalingham ◽  
A Mostyn ◽  
D S Gardner ◽  
T Stephenson ◽  
M E Symonds
Keyword(s):  
Uncoupling Protein ◽  
Developmental Regulation ◽  
Mitochondrial Protein ◽  
Later Life ◽  
Cord Compression ◽  
Nutrient Restriction ◽  
Mitochondrial Uncoupling ◽  
Glucocorticoid Sensitivity ◽  
The Impact ◽  
Glucocorticoid Action

Glucocorticoid action has a major role in regulating fetal and postnatal lung development, although its impact on mitochondrial development is less well understood. Critically, the consequences of any change in glucocorticoid action and mitochondrial function in early life may not be limited to the postnatal period, but may extend into later life. This paper focuses on more recent findings on the impact of ontogeny, fetal cortisol status, maternal nutrient restriction and postnatal leptin administration on mitochondrial uncoupling protein (UCP)-2, glucocorticoid receptor (GR) and 11 β-hydroxysteroid dehydrogenase type 1 (11βHSD1) isoform abundance in the lung. For example, in sheep, GR and 11βHSD1 mRNA are maximal at 140 days’ gestation (term ~147 days), while UCP2 mRNA peaks at 1 day after birth and then decreases with advancing age. In the fetus, chronic umbilical cord compression enhances the abundance of these genes, an outcome that can also be produced after birth following chronic, but not acute, leptin administration. Irrespective of the timing of maternal nutrient restriction in pregnancy, glucocorticoid sensitivity and UCP2 abundance are both upregulated in the lungs of the resulting offspring. In conclusion, prenatal and postnatal endocrine challenges have distinct effects on mitochondrial development in the lung resulting from changes in glucocorticoid action, which can persist into later life. As a consequence, changes in glucocorticoid sensitivity and mitochondrial protein abundance have the potential to be used to identify those at greatest risk of developing later lung disease.

scholarly journals Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta

Reproduction ◽  
2007 ◽  
Vol 134 (4) ◽  
pp. 615-623 ◽  
Author(s):  
M G Gnanalingham ◽  
P Williams ◽  
V Wilson ◽  
J Bispham ◽  
M A Hyatt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Mrna Abundance ◽  
Uncoupling Protein 2 ◽  
Type I ◽  
Voltage Dependent Anion Channel ◽  
Glucocorticoid Sensitivity ◽  
Ucp2 Mrna ◽  
Glucocorticoid Action

In sheep, modest maternal nutrient restriction (NR) over the period of rapid placental growth restricts placentome growth and results in offspring in which glucocorticoid action is enhanced. Therefore, this study investigated the placental effects of early to mid-gestational NR on glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), uncoupling protein-2 (UCP2), and IGF type-I receptor (IGF-IR) mRNA abundance together with cell proliferation and apoptosis as determined histologically, and the mitochondrial proteins voltage-dependent anion channel and cytochrome c that are involved in apoptosis. Placenta was sampled at 80 and 140 days gestation (dGA; term ~147 dGA). NR was imposed between 28 and 80 days gestation when control and nutrient-restricted groups consumed 150 or 60% respectively of their total metabolizable energy requirements. All mothers were then fed to requirements up to term. Total fetal placentome weights were decreased by NR at 80 dGA but were heavier at 140 dGA following 60 days of nutritional rehabilitation. GR and UCP2 mRNA abundance increased whilst 11βHSD2 mRNA decreased with gestational age. NR persistently up-regulated GR and UCP2 mRNA abundance. 11βHSD2 mRNA was reduced by NR at 80 dGA but increased near to term. IGF-IRmRNA abundance was only decreased at 80 dGA. Placental apoptosis and mitochondrial protein abundance were unaffected by NR, whereas cell proliferation was markedly reduced. In conclusion, placental UCP2 and local glucocorticoid action are affected by the gestational nutritional status and may result in the offspring showing enhanced glucocorticoid sensitivity, thereby predisposing them to disease in later life.

scholarly journals Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1241-1252 ◽  
Author(s):  
D P Yakubu ◽  
A Mostyn ◽  
V Wilson ◽  
S Pearce ◽  
M C Alves-Guerra ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Late Pregnancy ◽  
Mitochondrial Proteins ◽  
Nutrient Restriction ◽  
Voltage Dependent Anion Channel ◽  
Pregnant Sheep ◽  
Liver And Kidney

Adaptation to the extrauterine environment at birth relies upon the onset of postnatal function and increased metabolism in the lungs, liver and kidney, mediated partly by activation of mitochondrial proteins such as the voltage-dependent anion channel (VDAC), cytochromecand, in the lung only, uncoupling protein (UCP)2. The magnitude of adaptation is dependent on the maternal metabolic and endocrine environment. We, therefore, examined the influence of maternal cold exposure (MCE) induced by winter shearing of pregnant sheep in conjunction with nutrient restriction (NR; 50% reduction in maternal food intake from 110 days gestation up to term). The effect of parity was also examined, as the offspring of nulliparous mothers are growth restricted compared with multiparous offspring. All sheep were twin bearing. One twin was sampled after birth and its sibling at 30 days. In the lung, both MCE and maternal nulliparity enhanced UCP2 abundance. However, whilst VDAC abundance was decreased in both the offspring of nulliparous mothers and by NR, it was transiently raised by MCE. Kidney VDAC abundance was reduced by MCE and nulliparity, adaptations only influenced by NR in multiparous mothers. Cytochromecabundance was raised by MCE and by NR in multiparous controls and raised in offspring of nulliparous mothers. Liver VDAC and cytochromecabundance were transiently reduced by MCE and persistently lower in offspring of nulliparous mothers. In conclusion, changes in the maternal metabolic environment have marked tissue-specific effects on mitochondrial protein abundance in the lungs, liver and kidney that may be important in enabling the newborn to effectively adapt to the extrauterine environment.

scholarly journals The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-γ and cell proliferation

Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 601-608 ◽  
Author(s):  
M Yiallourides ◽  
S P Sebert ◽  
V Wilson ◽  
D Sharkey ◽  
S M Rhind ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Fetal Growth ◽  
Uncoupling Protein ◽  
Nutrient Restriction ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Differential Effects ◽  
Glucocorticoid Sensitivity ◽  
Ovine Placenta

Nutrient restriction (NR) during critical windows of pregnancy has differential effects on placento-fetal growth and development. Our study, therefore, investigated developmental and metabolic adaptations within the ovine placenta following NR at different critical windows during the first 110 days of gestation (term=147 days). Thus, the effects of NR on cell proliferation, glucocorticoid sensitivity, IGF1 and 2 receptor, peroxisome proliferator-activated receptor γ (PPARG), and uncoupling protein (UCP)2 gene expression in the placenta were examined. Singleton bearing sheep (n=4–8 per group) were fed either 100% of their total metabolizable energy requirements throughout the study or 50% of this amount between 0–30, 31–65, 66–110, and 0–110 days gestation. A significant reduction in cell proliferation and increased gene expression for the glucocorticoid and IGF2 receptors, PPARG, and UCP2 were detected in placentae sampled from mothers who were nutrient restricted between days 66 and 110 of gestation, only, relative to controls. This window of gestation coincides with the maximum placental growth and the start of exponential growth of the fetus when there are substantially increased metabolic demands on the placenta compared with earlier in gestation. Consequently, increased glucocorticoid sensitivity and suppressed IGF2 action could contribute to a switch in the placenta from proliferation to differentiation, thereby improving its nutrient transfer capacity. Upregulation of PPARG and UCP2 would promote placental fatty acid metabolism thereby limiting glucose utilization. These compensatory placental responses may serve to maintain fetal growth but could result in adverse adaptations such as the early onset of the metabolic syndrome in later life.

The thermogenic and metabolic responses to photoperiod manipulations in Apodemus chevrieri

2013 ◽  
Vol 63 (3) ◽  
pp. 241-255 ◽  
Author(s):  
Wan-long Zhu ◽  
Lin Zhang ◽  
Zheng-kun Wang
Keyword(s):  
Body Mass ◽  
Uncoupling Protein ◽  
Resting Metabolic Rate ◽  
Mitochondrial Protein ◽  
Short Photoperiod ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Adipose Tissues ◽  
Serum Leptin ◽  
Brown Adipose

Environmental cues play important roles in the regulation of an animal’s physiology and behavior. In the present study, we examined the effects of short photoperiod on body weight as well as on several physiological, hormonal, and biochemical measures indicative of thermogenic capacity to test our hypothesis that short photoperiod stimulates increases in thermogenesis without cold stress in Apodemus chevrieri. A. chevrieri were randomly assigned to either a long or short photoperiod for 4 weeks at constant temperature. The short photoperiod group of A. chevrieri showed increases in resting metabolic rate and nonshivering thermogenesis during the 4-week photoperiod acclimation. At the end, A. chevrieri at short photoperiod had lower body weights, higher levels of mitochondrial protein content and cytochrome C oxidase activity in liver and brown adipose tissues, and had higher levels of mitochondrial uncoupling protein-1 contents in brown adipose tissues. No difference in serum leptin levels were found between short and long photoperiod groups, but serum leptin levels were positively correlated with body mass and body fat mass, and negatively correlated with energy intake and uncoupling protein-1 content in brown adipose tissues, respectively. All results suggest that the short photoperiod may induce an increased thermogenesis capacity in A. chevrieri and that leptin is potentially involved in the photoperiod induced body mass regulation and thermogenesis in A. chevrieri.

Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2

2005 ◽  
Vol 289 (5) ◽  
pp. R1407-R1415 ◽  
Author(s):  
Muhuntha G. Gnanalingham ◽  
Alison Mostyn ◽  
Michael E. Symonds ◽  
Terence Stephenson
Keyword(s):  
Adipose Tissue ◽  
Fat Mass ◽  
Uncoupling Protein ◽  
Mrna Abundance ◽  
Late Gestation ◽  
Nutrient Restriction ◽  
Strongly Correlated ◽  
Perirenal Adipose Tissue ◽  
Glucocorticoid Action

Increased glucocorticoid action and adipose tissue inflammation contribute to excess adiposity. These adaptations may be enhanced in offspring exposed to nutrient restriction (NR) in utero, thereby increasing their susceptibility to later obesity. We therefore determined the developmental ontogeny of glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2, and uncoupling protein (UCP)-2 mRNA in perirenal adipose tissue between late gestation and 6 mo after birth in the sheep, as well as the effect of maternal NR targeted between early to mid (28–80 days, term ∼147 days)- or late (110–147 days) gestation. GR and 11βHSD1 mRNA increased with fat mass and were all maximal within the 6-mo observation period. 11βHSD2 mRNA abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and 11βHSD1 mRNA abundance were strongly correlated with total and relative perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and 11βHSD1 mRNA. Early- to midgestational NR increased GR, 11βHSD1, and UCP2 mRNA, but decreased 11βHSD2 mRNA abundance, an adaptation reversed with late-gestational NR. We conclude that the continual rise in glucocorticoid action and fat mass after birth may underlie the development of later obesity. The magnitude of this adaptation is partly dependent on maternal food intake through pregnancy.

scholarly journals Maternal manipulation of brown adipose tissue and liver development in the ovine fetus during late gestation

1997 ◽  
Vol 77 (6) ◽  
pp. 871-883 ◽  
Author(s):  
Lynne Clarke ◽  
Michael J. Bryant ◽  
Michael A. Lomax ◽  
Michael E. Symonds
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Late Gestation ◽  
Liver Development ◽  
Type I ◽  
Mitochondrial Uncoupling ◽  
Brown Adipose

AbstractWe examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126,140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possesd more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5 deiodinas(EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine Sdeiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development

scholarly journals Tissue-specific effects of leptin administration on the abundance of mitochondrial proteins during neonatal development

2005 ◽  
Vol 187 (1) ◽  
pp. 81-88 ◽  
Author(s):  
M G Gnanalingham ◽  
A Mostyn ◽  
J Wang ◽  
R Webb ◽  
D H Keisler ◽  
...  
Keyword(s):  
Protein Function ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Later Life ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Voltage Dependent Anion Channel ◽  
Tissue Specific ◽  
The Brain

Many tissues undergo a rapid transition after birth, accompanied by dramatic changes in mitochondrial protein function. In particular, uncoupling protein (UCP) abundance increases at birth in the lung and adipose tissue, to then gradually decline, an adaptation that is important in enabling normal tissue function. Leptin potentially mediates some of these changes and is known to promote the loss of UCP1 from brown fat but its effects on UCP2 and related mitochondrial proteins (i.e. voltage-dependent anion channel (VDAC) and cytochrome c) in other tissues are unknown. We therefore determined the effects of once-daily jugular venous administration of ovine recombinant leptin on mitochondrial protein abundance as determined by immunoblotting in tissues that do (i.e. the brain and pancreas) and do not (i.e. liver and skeletal muscle) express UCP2. Eight pairs of 1-day-old lambs received either 100 μg leptin or vehicle daily for 6 days, before tissue sampling on day 7. Administration of leptin diminished UCP2 abundance in the pancreas, but not the brain. Leptin administration had no affect on the abundance of VDAC or cytochrome c in any tissue examined. In leptin-administered animals, but not controls, UCP2 abundance in the pancreas was positively correlated with VDAC and cytochrome c content, and UCP2 abundance in the brain with colonic temperature. In conclusion, leptin administration to neonatal lambs causes a tissue-specific loss of UCP2 from the pancreas. These effects may be important in the regulation of neonatal tissue development and potentially for optimising metabolic control mechanisms in later life.

A mitochondrial uncoupling artifact can be caused by expression of uncoupling protein 1 in yeast

2001 ◽  
Vol 356 (3) ◽  
pp. 779-789 ◽  
Author(s):  
Jeff A. STUART ◽  
James A. HARPER ◽  
Kevin M. BRINDLE ◽  
Mika B. JEKABSONS ◽  
Martin D. BRAND
Keyword(s):  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Physiological Property ◽  
Growth Defect ◽  
Yeast Mitochondria ◽  
Proton Conductance ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Carrier ◽  
Brown Adipose

Uncoupling protein 1 (UCP1) from mouse was expressed in yeast and the specific (GDP-inhibitable) and artifactual (GDP-insensitive) effects on mitochondrial uncoupling were assessed. UCP1 provides a GDP-inhibitable model system to help interpret the uncoupling effects of high expression in yeast of other members of the mitochondrial carrier protein family, such as the UCP1homologues UCP2 and UCP3. Yeast expressing UCP1 at modest levels (approx. 1μg/mg of mitochondrial protein) showed no growth defect, normal rates of chemically uncoupled respiration and an increased non-phosphorylating proton conductance that was completely GDP-sensitive. The catalytic-centre activity of UCP1 in these yeast mitochondria was similar to that in mammalian brown-adipose-tissue mitochondria. However, yeast expressing UCP1 at higher levels (approx. 11μg/mg of mitochondrial protein) showed a growth defect. Their mitochondria had depressed chemically uncoupled respiration rates and an increased proton conductance that was partly GDP-insensitive. Thus, although UCP1 shows native behaviour at modest levels of expression in yeast, higher levels (or rates) of expression can lead to an uncoupling that is not a physiological property of the native protein and is therefore artifactual. This observation might be important in the interpretation of results from experiments in which the functions of UCP1homologues are verified by their ability to uncouple yeast mitochondria.

Adaptive changes in the concentration of the mitochondrial ‘uncoupling’ protein in brown adipose tissue of hamsters acclimated at different temperatures

1983 ◽  
Vol 3 (12) ◽  
pp. 1077-1084 ◽  
Author(s):  
Paul Trayhurn ◽  
Denis Richard ◽  
Graham Jennings ◽  
Margaret Ashwell
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Mitochondrial Uncoupling ◽  
Interscapular Brown Adipose Tissue ◽  
Adaptive Changes ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Different Temperatures

The effect of acclimation at different temperatures on the activity of interscapular brown adipose tissue has been investigated in the hamster, a hibernator. Between 31° and 4°C the cytochrome oxidase activity of the tissue increased 4- to 5-fold, mitochondrial GDP binding per mg of mitochondrial protein doubled, and the amount of uncoupling protein rose from 1.7% to 5.4% of total mitochondrial protein. It is concluded that there are clear adaptive changes induced by temperature in brown adipose tissue of the hamster, but the changes are limited in comparison with those in the mouse.

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

2012 ◽  
Vol 302 (9) ◽  
pp. E1123-E1141 ◽  
Author(s):  
Aurélia De Pauw ◽  
Stéphane Demine ◽  
Silvia Tejerina ◽  
Marc Dieu ◽  
Edouard Delaive ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Pyruvate Carboxylase ◽  
Mitochondrial Protein ◽  
Functional Study ◽  
Mitochondrial Uncoupling ◽  
Triglyceride Accumulation ◽  
Qualitative Approaches ◽  
Mitochondrial Dna Copy Number ◽  
Triglyceride Content ◽  
The Impact

In adipocytes, mitochondrial uncoupling is known to trigger a triglyceride loss comparable with the one induced by TNFα, a proinflammatory cytokine. However, the impact of a mitochondrial uncoupling on the abundance/composition of mitochondria and its connection with triglyceride content in adipocytes is largely unknown. In this work, the effects of a mild mitochondrial uncoupling triggered by FCCP were investigated on the mitochondrial population of 3T3-L1 adipocytes by both quantitative and qualitative approaches. We found that mild mitochondrial uncoupling does not stimulate mitochondrial biogenesis in adipocytes but induces an adaptive cell response characterized by quantitative modifications of mitochondrial protein content. Superoxide anion radical level was increased in mitochondria of both TNFα- and FCCP-treated adipocytes, whereas mitochondrial DNA copy number was significantly higher only in TNFα-treated cells. Subproteomic analysis revealed that the abundance of pyruvate carboxylase was reduced significantly in mitochondria of TNFα- and FCCP-treated adipocytes. Functional study showed that overexpression of this major enzyme of lipid metabolism is able to prevent the triglyceride content reduction in adipocytes exposed to mitochondrial uncoupling or TNFα. These results suggest a new mechanism by which the effects of mitochondrial uncoupling might limit triglyceride accumulation in adipocytes.

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