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 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 Differential Association of Uncoupling Protein 2 Polymorphisms with Pattern Identification among Korean Stroke Patients: A Diagnostic System in Traditional Korean Medicine

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ji Hye Lim ◽  
Mi Mi Ko ◽  
Hoyoung Lee ◽  
Ho Yeon Go ◽  
Tae-Woong Moon ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Diagnostic System ◽  
Cell Types ◽  
Pattern Identification ◽  
Uncoupling Protein 2 ◽  
Stroke Patients ◽  
Standard Pattern ◽  
Yin Deficiency ◽  
Predictive Parameters

Uncoupling protein 2 (UCP2), a mitochondrial protein present in many organs and cell types, is known to dissipate the proton gradient formed by the electron transport chain. Its function is correlated with predictive parameters, such as obesity, diabetes, and metabolic syndromes. We analyzed the distribution of UCP2 polymorphisms in stroke patients diagnosed with one of the following four stroke subtypes based on the TKM standard pattern identification (PI): Qi-deficiency (QD), Dampness and Phlegm (D&P), Yin-deficiency (YD), and Fire and Heat (F&D). We studied a total of 1,786 stroke patients (397/QD, 645/D&P, 223/YD, and 522/F&D, 586/normal). Genotyping for the G-1957A, G-866A and A55V UCP2 polymorphisms was performed using the TaqMan. G-866A and A55V were significantly associated with the D&P and H&F subtypes. The frequency of subjects with the A allele of G-866A was significantly lower than the frequency of subjects with the GG type. The A55V polymorphism was also shown similar effect with G-866A in the dominant model. In contrast, no SNPs were shown to be associated with the QD or YD subtypes in this study. These results showed that the G-866A and A55V UCP2 polymorphisms may be genetic factors for specific PI types among Korean stroke patients.

scholarly journals Quantification of Uncoupling Protein 2 Reveals Its Main Expression in Immune Cells and Selective Up-Regulation during T-Cell Proliferation

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e41406 ◽  
Author(s):  
Anne Rupprecht ◽  
Anja U. Bräuer ◽  
Alina Smorodchenko ◽  
Justus Goyn ◽  
Karolina E. Hilse ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Immune Cells ◽  
Uncoupling Protein ◽  
T Cell Proliferation ◽  
Uncoupling Protein 2

scholarly journals Uncoupling Protein-2 Decreases the Lipogenic Actions of Ghrelin

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2078-2086 ◽  
Author(s):  
Zane B. Andrews ◽  
Derek M. Erion ◽  
Rudolph Beiler ◽  
Charles S. Choi ◽  
Gerald I. Shulman ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Fat Metabolism ◽  
Mitochondrial Protein ◽  
Fat Oxidation ◽  
Negative Energy ◽  
Increase Body Weight ◽  
Ucp2 Mrna

The exact mechanisms through which ghrelin promotes lipogenesis are unknown. Uncoupling protein (UCP)-2 is a mitochondrial protein important in regulating reactive oxygen species; however, recent research shows that it may play an important role fat metabolism. Given that ghrelin increases UCP2 mRNA in white adipose tissue, we examined whether the lipogenic actions of ghrelin are modulated by UCP2 using ucp2+/+ and ucp2−/− mice. Chronic ghrelin treatment either via osmotic minipumps or daily ip injections induced body weight gain in both ucp2+/+ and ucp2−/− mice; however, body weight gain was potentiated in ucp2−/− mice. Increased body weight gain was completely due to increased body fat as a result of decreased fat oxidation in ucp2−/− mice. Ghrelin treatment of ucp2−/− mice resulted in a gene expression profile favoring lipogenesis. In a calorie-restriction model of negative energy balance, ghrelin to ucp2+/+ mice did not increase body weight; however, ghrelin to ucp2−/− mice still induced body weight. These results show that UCP2 plays an important role in fat metabolism by promoting fat oxidation and restricts ghrelin-induced lipogenesis.

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.

Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion

2004 ◽  
Vol 286 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
Hua Wang ◽  
Winston S. Chu ◽  
Tong Lu ◽  
Sandra J. Hasstedt ◽  
Philip A. Kern ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Mrna Levels ◽  
Metabolic Study ◽  
Β Cell ◽  
Family Based ◽  
Ucp2 Mrna

The onset of type 2 diabetes (T2DM) is preceded by obesity, insulin resistance, and impaired β-cell function. Uncoupling protein-2 (UCP2) is a widely expressed inner mitochondrial membrane protein. Common polymorphisms of the UCP2 gene have been implicated in diabetes, in obesity, and with changes in UCP2 mRNA levels. We tested the hypothesis that common UCP2 variants influence T2DM susceptibility in four parallel studies of separate populations. We typed the -866 promoter (G/A) variant, a nonsynonymous (Ala55Val or A55V) single-nucleotide polymorphism in exon 4, and a 45-nt insertion in the 3′-untranslated (3′UTR) region. Study populations included a case-control population study, a family-based association study, and a metabolic study of individuals who had been characterized for insulin sensitivity and secretion. To evaluate UCP2 mRNA levels, we examined a fourth population of subjects, who had undergone subcutaneous fat biopsy. All three variants showed a trend to an association with T2DM ( P = 0.05 to 0.07) in the population but not the family-based association study. The 3′ insertion/deletion (3′UTR I/D) variant was associated with body mass index (BMI, P = 0.035) among nondiabetic family members. Haplotype combinations were significantly associated with BMI ( P = 0.028), triglyceride levels ( P = 0.026), and fasting insulin ( P = 0.029); highest values for the three traits were observed in individuals with the heterozygous combination GVI/AVD. In the metabolic study, all three variants were associated with an index of β-cell compensation for insulin sensitivity (disposition index), particularly in interaction with family membership ( P < 0.000001). Individuals homozygous for the -866 A allele had decreased adipose mRNA levels relative to GG homozygous individuals ( P = 0.009), but the 3′UTR I/D variant had no impact on mRNA levels. We confirm modest effects of UCP2 variants on BMI and T2DM and show significant effects on insulin secretion in interaction with family-specific factors. However, the associated allele and the effects on gene expression are opposite to those reported previously.

scholarly journals Uncoupling protein 2 mRNA expression and respiratory parameters in Kupffer cells isolated from euthyroid and hyperthyroid rat livers

2001 ◽  
Vol 145 (3) ◽  
pp. 317-322 ◽  
Author(s):  
A Voci ◽  
I Demori ◽  
AT Franzi ◽  
E Fugassa ◽  
F Goglia ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Mitochondrial Respiration ◽  
Uncoupling Protein ◽  
Liver Perfusion ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Uncoupling Protein 2 ◽  
Mrna Levels ◽  
Respiratory Parameters ◽  
Ucp2 Mrna

OBJECTIVE: The levels of uncoupling protein 2 (UCP2) mRNA and determinants of respiration (ATP synthesis, proton leak and non-mitochondrial respiration) were evaluated in Kupffer cells isolated from the livers of normal euthyroid, acute hyperthyroid and chronic hyperthyroid rats. METHODS: After liver perfusion, Kupffer cells were purified by density-gradient centrifugation followed by counterflow centrifugal elutriation. UCP2 mRNA levels were measured by Northern blot and respiratory parameters by polarographic method. RESULTS: In cells isolated from hyperthyroid (tri-iodothyronine (T(3))-treated) rats, the effect of T(3) treatment on the UCP2 mRNA level varied: it was more than doubled (P<0.05) in acutely T(3)-treated rats but, after chronic (3-week) T(3) treatment, it was only 30% (not statistically significant) above the control (euthyroid) level. In Kupffer cells from the livers of chronic hyperthyroid rats, we observed an increase in total respiration rate, with an increase in the percentage attributable to the proton leak and a corresponding decrease in the percentage attributable to ATP synthesis (no alteration was observed in the percentage attributable to non-mitochondrial respiration). In the acute hyperthyroid rats, no significant differences were observed in any of the respiratory parameters, although they all tended to increase. CONCLUSION: These data are indicative of a possible uncoupling effect of UCP2 in Kupffer cells. T(3), by enhancing the expression of UCP2, could play a role in the energy homeostasis of these cells.

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