Modulatory effect of leptin on nitric oxide production and lipid metabolism in term placental tissues from control and streptozotocin-induced diabetic rats

2004 ◽  
Vol 16 (3) ◽  
pp. 363 ◽  
Author(s):  
Verónica White ◽  
Elida González ◽  
Evangelina Capobianco ◽  
Carolina Pustovrh ◽  
Carlos Soñez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Metabolism ◽  
De Novo ◽  
Lipid Synthesis ◽  
Placental Tissue ◽  
Diabetic Rats ◽  
Late Gestation ◽  
Diabetic Rat ◽  
No Production

Leptin production by placental tissues contributes to its circulating levels and functions. The diabetic pathology induces alterations in leptin levels. In the present study, leptin levels were evaluated in placental tissue from control and neonatal streptozotocin-induced (n-STZ) diabetic rats during late gestation. The effects of leptin levels on the generation of nitric oxide (NO), prostaglandin (PG) E2 production and lipid metabolism were examined. Leptin levels were diminished in placentas from n-STZ diabetic rats compared with controls (P < 0.01). These differences were also evident when leptin was evaluated immunohistochemically. Addition of leptin (1 nm) in vitro enhanced NO production in control (66%) and diabetic placentas (134%) by stimulating NO synthase activity (by 38% and 54%, respectively). The addition of leptin increased PGE2 production in placentas from control (173%) and diabetic rats (83%) and produced a 50% decrease in placental lipid levels (phospholipids, triacylglycerides, cholesterol and cholesteryl ester) without involving a reduction in de novo lipid synthesis. These data indicate that leptin enhances the production of placental NO and PGE2, vasoactive agents that modify placental blood flow, and that leptin stimulates placental lipid metabolism, probably generating more lipids for transfer to the fetus. In the diabetic rat, placental leptin was reduced, probably as a response to the maternal environment to locally regulate the transfer of nutrients to the developing fetus.

15-Deoxy-Δ12,14-prostaglandin J2 and peroxisome proliferator-activated receptor γ (PPARγ) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARγ agonist on nitridergic and lipid placental metabolism

2005 ◽  
Vol 17 (4) ◽  
pp. 423 ◽  
Author(s):  
E. Capobianco ◽  
A. Jawerbaum ◽  
M. C. Romanini ◽  
V. White ◽  
C. Pustovrh ◽  
...  
Keyword(s):  
De Novo ◽  
Lipid Synthesis ◽  
Diabetic Rats ◽  
Lipid Homeostasis ◽  
Diabetic Rat ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Prostaglandin J2

15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor γ (PPARγ) ligand that regulates lipid homeostasis and has anti-inflammatory properties in many cell types. We postulated that 15dPGJ2 may regulate lipid homeostasis and nitric oxide (NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes-induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin-induced diabetic rats, 15dPGJ2 concentrations were decreased (83%) and immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/nitrites (an index of NO production) were diminished (40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPARγ activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of 14C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPARγ activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPARγ. We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPARγ were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.

Leptin modulates nitric oxide production and lipid metabolism in human placenta

2006 ◽  
Vol 18 (4) ◽  
pp. 425 ◽  
Author(s):  
Verónica White ◽  
Elida González ◽  
Evangelina Capobianco ◽  
Carolina Pustovrh ◽  
Nora Martínez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Metabolism ◽  
Human Placenta ◽  
De Novo ◽  
Primary Cultures ◽  
Lipid Synthesis ◽  
No Production ◽  
Dependent Manner ◽  
Lipid Catabolism

Leptin has significant effects on appetite, energy expenditure, lipid mobilisation and reproduction. During pregnancy, leptin is produced in the placenta, a tissue in which leptin receptors are highly expressed, suggesting autocrine/paracrine functions for this hormone. In the present study, a putative role of leptin as a regulator of nitric oxide (NO) production and lipid metabolism was evaluated in term human placenta. We demonstrated that leptin enhanced NO production in human placental explants (P < 0.01). Although leptin did not modify the placental levels of cholesteryl esters and phospholipids, leptin decreased levels of triglycerides (P < 0.01) and cholesterol (P < 0.001) in term human placenta. The effect of leptin on lipid mass seems to be independent of the modulation of de novo lipid synthesis because leptin did not modify the incorporation of 14C-acetate into any of the lipids evaluated. We investigated the effects of leptin on placental lipid catabolism and found that in both term human placental explants and primary cultures of trophoblastic cells, leptin increased glycerol release, an index of the hydrolysis of esterified lipids, in a dose-dependent manner. In conclusion, we have shown that leptin affects NO production and lipid catabolism in human placenta, providing supportive evidence for a role of leptin in placental functions that would determine the transfer of nutrients to the developing fetus.

scholarly journals PPARα agonists regulate lipid metabolism and nitric oxide production and prevent placental overgrowth in term placentas from diabetic rats

2011 ◽  
Vol 47 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Nora Martínez ◽  
Melisa Kurtz ◽  
Evangelina Capobianco ◽  
Romina Higa ◽  
Verónica White ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Metabolism ◽  
Lipid Synthesis ◽  
Diabetic Rats ◽  
Placental Weight ◽  
Peroxidation Of Lipids ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Regulate Lipid Metabolism

Maternal diabetes impairs fetoplacental metabolism and growth. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor capable of regulating lipid metabolism and inflammatory pathways. In this study, we analyzed whether placental and fetal PPARα activation regulates lipid metabolism and nitric oxide (NO) production in term placentas from diabetic rats. Diabetes was induced by neonatal streptozotocin administration. On day 21 of pregnancy, placentas from control and diabetic rats were cultured in the presence of PPARα agonists (clofibrate and leukotriene B4 (LTB4)) for further evaluation of levels, synthesis, and peroxidation of lipids as well as NO production. Besides, on days 19, 20, and 21 of gestation, fetuses were injected with LTB4, and the placentas were explanted on day 21 of gestation for evaluation of placental weight and concentrations of placental lipids, lipoperoxides, and NO metabolites. We found that placentas from diabetic rats showed reduced PPARα concentrations. They presented no lipid overaccumulation but reduced lipid synthesis, parameters negatively regulated by PPARα activators. Lipid peroxidation and NO production, increased in placentas from diabetic rats, were negatively regulated by PPARα activators. Fetal PPARα activation in diabetic rats does not change placental lipid concentrations but reduced placental weight and NO production. In conclusion, PPARα activators regulate lipid metabolism and NO production in term placentas from diabetic rats, an activation that regulates placental growth and can partly be exerted by the developing fetus.

Pulmonary endothelial nitric oxide production is developmentally regulated in the fetus and newborn

1993 ◽  
Vol 265 (4) ◽  
pp. H1056-H1063 ◽  
Author(s):  
P. W. Shaul ◽  
M. A. Farrar ◽  
R. R. Magness
Keyword(s):  
Nitric Oxide ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Late Gestation ◽  
No Production ◽  
Third Trimester ◽  
Developmentally Regulated ◽  
The Third ◽  
Endothelial Nitric Oxide

To define the role of endothelial nitric oxide (NO) in developmental changes in pulmonary vascular resistance and oxygen responsiveness, we determined the ontogeny of endothelial NO production and of oxygen modulation of that process in pulmonary arteries from fetal and newborn lambs. NO production was assessed by measuring endothelium-dependent arterial guanosine 3',5'-cyclic monophosphate synthesis. Basal NO rose two-fold from late gestation to 1 wk of age and another 1.6-fold from 1 to 4 wk. Acetylcholine-stimulated NO also increased 1.6-fold from 1 to 4 wk. The maturational rise in NO was evident at high Po2 in vitro, and it was not modified by L-arginine. This suggests that the developmental increase may alternatively involve enhanced calcium-calmodulin-mediated mechanisms, increased expression of NO synthase, or greater availability of required cofactor(s). With an acute decline in Po2 in vitro from 680 to 150 or 40 mmHg, there was 50-88% attenuation of basal and acetylcholine-stimulated NO late in the third trimester and in the newborn but not early in the third trimester. Parallel studies of mesenteric endothelium revealed postnatal increases in basal and stimulated NO but no decline in NO at lower Po2. Ontogenic changes in endothelial NO production and in oxygen modulation of that process may be involved in the maturational decrease in vascular resistance and the development of oxygen responsiveness in the pulmonary circulation.

scholarly journals SLC25A1 promotes tumor growth and survival by reprogramming energy metabolism in colorectal cancer

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Ying Yang ◽  
Jiaxing He ◽  
Bo Zhang ◽  
Zhansheng Zhang ◽  
Guozhan Jia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Energy Metabolism ◽  
Cell Apoptosis ◽  
De Novo ◽  
Lipid Synthesis ◽  
Growth And Survival ◽  
Metabolism Regulation

AbstractAbnormal lipid metabolism has been commonly observed in various human cancers, including colorectal cancer (CRC). The mitochondrial citrate carrier SLC25A1 (also known as mitochondrial citrate/isocitrate carrier, CIC), has been shown to play an important role in lipid metabolism regulation. Our bioinformatics analysis indicated that SLC25A1 was markedly upregulated in CRC. However, the role of SLC25A1 in the pathogenesis and aberrant lipid metabolism in CRC remain unexplored. Here, we found that SLC25A1 expression was significantly increased in tumor samples of CRC as compared with paired normal samples, which is associated with poor survival in patients with CRC. Knockdown of SLC25A1 significantly inhibited the growth of CRC cells by suppressing the progression of the G1/S cell cycle and inducing cell apoptosis both in vitro and in vivo, whereas SLC25A1 overexpression suppressed the malignant phenotype. Additionally, we demonstrated that SLC25A1 reprogrammed energy metabolism to promote CRC progression through two mechanisms. Under normal conditions, SLC25A1 increased de novo lipid synthesis to promote CRC growth. During metabolic stress, SLC25A1 increased oxidative phosphorylation (OXPHOS) to protect protects CRC cells from energy stress-induced cell apoptosis. Collectively, SLC25A1 plays a pivotal role in the promotion of CRC growth and survival by reprogramming energy metabolism. It could be exploited as a novel diagnostic marker and therapeutic target in CRC.

scholarly journals Modulation of nitric oxide concentration and lipid metabolism by 15-deoxy Delta12,14prostaglandin J2 in embryos from control and diabetic rats during early organogenesis

Reproduction ◽  
2002 ◽  
pp. 625-631 ◽  
Author(s):  
A Jawerbaum ◽  
D Sinner ◽  
V White ◽  
C Pustovrh ◽  
E Capobianco ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cholesteryl Ester ◽  
De Novo ◽  
Lipid Synthesis ◽  
Diabetic Rats ◽  
Diabetic Model ◽  
Early Organogenesis ◽  
Oxide Concentration ◽  
Nitric Oxide Concentration ◽  
Nitrate And Nitrite

The concentration of 15-deoxy Delta(12,14)PGJ(2) (15dPGJ(2)) and its effects on nitric oxide generation and neutral lipid in embryos from control and neonatal streptozotocin-induced (n-stz) diabetic rats during organogenesis were investigated. 15dPGJ(2) is produced in embryos during organogenesis, and its production is lower in embryos of n-stz diabetic rats than in embryos from control rats. Nitrate and nitrite concentrations were higher in embryos from n-stz diabetic rats and were reduced in the presence of 15dPGJ(2) both in embryos from control and diabetic rats. Thus, decreased 15dPGJ(2) concentrations in embryos from n-stz diabetic rats may be related to the high nitric oxide concentrations found in those embryos. Exogenous 15dPGJ(2) decreased cholesterol and cholesteryl ester concentrations in embryos from control and n-stz diabetic rats, and reduced triacylglycerol concentrations in control embryos. Incorporation of [(14)C]acetate into lipids showed decreased de novo synthesis of cholesteryl ester and triacylglycerides in embryos from n-stz diabetic rats compared with controls. Exogenous 15dPGJ(2) reduced the incorporation of [(14)C]acetate into triacylglycerides, cholesterol and cholesteryl ester in embryos from both control and n-stz diabetic rats. 15dPGJ(2) is present in embryos during organogenesis, and reduces embryonic nitric oxide production and lipid synthesis. The lower 15dPGJ(2) concentration in embryos from n-stz diabetic rats may result in developmental alterations in this diabetic model.

Lipid metabolism in the embryos of diabetic rats during early organogenesis: modulatory effect of prostaglandin E2

2003 ◽  
Vol 15 (1) ◽  
pp. 75 ◽  
Author(s):  
Debora Sinner ◽  
J. Matías Caviglia ◽  
Alicia Jawerbaum ◽  
R. Ariel Igal ◽  
Elida Gonzalez
Keyword(s):  
Lipid Metabolism ◽  
Prostaglandin E2 ◽  
Lipid Profile ◽  
De Novo ◽  
Lipid Synthesis ◽  
Diabetic Rats ◽  
Lipid Classes ◽  
De Novo Synthesis ◽  
Lipid Species ◽  
Early Organogenesis

The purpose of this work was to evaluate de novo lipid biosynthesis and the lipid profile, and to study the effect of prostaglandin E2 (PGE2; prostaglandin has previously been found to be involved in diabetes embryopathy) on lipid metabolism in embryos from control and streptozotocin-induced diabetic rats during organogenesis. Increased levels of triacylglycerols were found in embryos of diabetic rats compared with controls, whereas no differences were detected in the levels of cholesterol, cholesterylester, phosphatidylcholine and phosphatidylethanolamine. When the de novo synthesis of lipids in the embryo was studied using [14C]acetate as a tracer, a diminished rate of incorporation of [14C]acetate into the evaluated lipid classes was detected in the diabetic embryo compared with controls. Addition of PGE2 did not modify the incorporation of [14C]acetate into any of the lipid species of control embryos, but enhanced the incorporation of [14C]acetate into triacylglycerol, cholesterylesters, phosphatidylcholine and phosphatidylethanolamine of embryos from diabetic rats. The study’s results show alterations in both synthesis and concentrations of lipids in the embryos of diabetic rats. Interestingly, the results demonstrate that the addition of PGE2, a prostaglandin that reverses the embryonic morphological abnormalities induced by diabetes, prevents disturbances in embryo lipid synthesis caused by diabetes.

scholarly journals Active and inactive pools of nNOS in the nerve terminals in mouse gut: implications for nitrergic neurotransmission

2008 ◽  
Vol 294 (3) ◽  
pp. G627-G634 ◽  
Author(s):  
Y. Manjula Rao ◽  
Arun Chaudhury ◽  
Raj K. Goyal
Keyword(s):  
Nitric Oxide ◽  
De Novo ◽  
In Vitro Assays ◽  
No Production ◽  
Nerve Terminals ◽  
De Novo Synthesis ◽  
Sds Page ◽  
Catalytically Active ◽  
Oxide Synthase

Nitric oxide (NO) is responsible for nitrergic neurotransmission in the gut, and its release is dependent on its de novo synthesis by neuronal nitric oxide synthase (nNOS). The magnitude of NO synthesis and release during neurotransmission may be related to the fraction of catalytically active nNOS out of a larger pool of inactive nNOS in the nerve terminals. The purpose of the present study was to identify catalytically active and inactive pools of nNOS in the varicosities from mouse gut. Enteric varicosities were confirmed as nitrergic by colocalization of nNOS with the nerve varicosity marker synaptophysin. Low-temperature SDS-PAGE of these varicosity extracts showed 320-, 250-, and 155-kDa bands when blotted with anti-nNOS1422–1433 and 320- and 155-kDa bands when blotted with anti-nNOS1–20 antibodies, respectively. The 320- and 155-kDa bands represent dimers and monomers of nNOSα; the 250- and 135-kDa bands represent dimers and monomers of nNOSβ. Immunoprecipitation with calmodulin (CaM) showed that a portion of nNOSα dimer was bound with CaM. On the other hand, a portion of nNOSα dimer, nNOSβ dimer, and all monomers lacked CaM binding. The CaM-lacking nNOS fractions reacted with anti-serine 847-phospho-nNOS. In vitro assays of NO production revealed that only the CaM-bound dimeric nNOSα was catalytically active; all other forms were inactive. We suggest that the amount of catalytically active nNOSα dimers may be regulated by serine 847 phosphorylation and equilibrium between dimers and monomers of nNOSα.

Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats

2004 ◽  
Vol 287 (4) ◽  
pp. R735-R741 ◽  
Author(s):  
Yunpeng Du ◽  
V. P. Sarthy ◽  
T. S. Kern
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Death ◽  
Diabetic Retinopathy ◽  
Diabetic Rats ◽  
No Production ◽  
Retinal Cells ◽  
Elevated Glucose ◽  
Cox 2

A nonselective inhibitor of cyclooxygenase (COX; high-dose aspirin) and a relatively selective inhibitor of inducible nitric oxide synthase (iNOS; aminoguanidine) have been found to inhibit development of diabetic retinopathy in animals, raising a possibility that NOS and COX play important roles in the development of retinopathy. In this study, the effects of hyperglycemia on retinal nitric oxide (NO) production and the COX-2 pathway, and the interrelationship of the NOS and COX-2 pathways in retina and retinal cells, were investigated using a general inhibitor of NOS [ NG-nitro-l-arginine methyl ester (l-NAME)], specific inhibitors of iNOS [l- N6-(1-iminoethyl)lysine (l-NIL)] and COX-2 (NS-398), and aspirin and aminoguanidine. In vitro studies used a transformed retinal Müller (glial) cell line (rMC-1) and primary bovine retinal endothelial cells (BREC) incubated in 5 and 25 mM glucose with and without these inhibitors, and in vivo studies utilized retinas from experimentally diabetic rats (2 mo) treated or without aminoguanidine or aspirin. Retinal rMC-1 cells cultured in high glucose increased production of NO and prostaglandin E2 (PGE2) and expression of iNOS and COX-2. Inhibition of NO production with l-NAME or l-NIL inhibited all of these abnormalities, as did aminoguanidine and aspirin. In contrast, inhibition of COX-2 with NS-398 blocked PGE2 production but had no effect on NO or iNOS. In BREC, elevated glucose increased NO and PGE2 significantly, whereas expression of iNOS and COX-2 was unchanged. Viability of rMC-1 cells or BREC in 25 mM glucose was significantly less than at 5 mM glucose, and this cell death was inhibited by l-NAME or NS-398 in both cell types and also by l-NIL in rMC-1 cells. Retinal homogenates from diabetic animals produced significantly greater than normal amounts of NO and PGE2 and of iNOS and COX-2. Oral aminoguanidine and aspirin significantly inhibited all of these increases. The in vitro results suggest that the hyperglycemia-induced increase in NO in retinal Müller cells and endothelial cells increases production of cytotoxic prostaglandins via COX-2. iNOS seems to account for the increased production of NO in Müller cells but not in endothelial cells. We postulate that NOS and COX-2 act together to contribute to retinal cell death in diabetes and to the development of diabetic retinopathy and that inhibition of retinopathy by aminoguanidine or aspirin is due at least in part to inhibition of this NO/COX-2 axis.

scholarly journals Effects of chitosan on nitric oxide production and inducible nitric oxide synthase activity and mRNA expression in weaned piglets

2018 ◽  
Vol 60 (No. 8) ◽  
pp. 359-366
Author(s):  
J. Li ◽  
B. Shi ◽  
S. Yan ◽  
L. Jin ◽  
Y. Guo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Inducible Nitric Oxide Synthase ◽  
No Production ◽  
Weaned Piglets ◽  
Inos Activity ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 &micro;g chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P &lt; 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P &lt; 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P&nbsp;&lt; 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P &lt; 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.

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