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 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.

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.

Signal transduction in EJ-H-ras -transformed cells: De novo synthesis of diacylglycerol and subversion of agonist-stimulated inositol lipid metabolism

FEBS Letters ◽  
1989 ◽  
Vol 252 (1-2) ◽  
pp. 129-134 ◽  
Author(s):  
Vincenzo P. Chiarugi ◽  
Lucia Magnelli ◽  
Franca Pasquali ◽  
Gabriele Basi ◽  
Marco Ruggiero
Keyword(s):  
Signal Transduction ◽  
Lipid Metabolism ◽  
De Novo ◽  
Transformed Cells ◽  
De Novo Synthesis

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 Apparent coordination of the biosynthesis of lipids in cultured cells: its relationship to the regulation of the membrane sterol:phospholipid ratio and cell cycling.

1980 ◽  
Vol 86 (3) ◽  
pp. 810-819 ◽  
Author(s):  
R B Cornell ◽  
A F Horwitz
Keyword(s):  
Cell Cycle ◽  
Cholesterol Synthesis ◽  
Cultured Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Lipid Classes ◽  
Sterol Synthesis ◽  
G1 Arrest ◽  
Proliferating Cells ◽  
Cell Cycling

The coordination of the syntheses of the several cellular lipid classes with one another and with cell cycle control were investigated in proliferating L6 myoblasts and fibroblasts (WI-38 and CEF). Cells cultured in lipid-depleted medium containing one of two inhibitors of hydroxymethylglutaryl-CoA reductase, 25-hydroxycholesterol or compactin, display a rapid, dose-dependent inhibition of cholesterol synthesis. Inhibition of the syntheses of each of the other lipid classes is first apparent after the rate of sterol synthesis is depressed severalfold. 24 h after the addition of the inhibitor, the syntheses of DNA, RNA, and protein also decline. The inhibition of sterol synthesis leads to a threefold reduction in the sterol:phospholipid ratio that parallels the development of proliferative and G1 cell cycle arrests and alterations in cellular morphology. All of these responses are reversed upon reinitiation of cholesterol synthesis or addition of exogenous cholesterol. A comparison of the timing of these responses with respect to the development of the G1 arrest indicates that the primary factor limiting cell cycling is the availability of cholesterol provided either from an exogenous source or by de novo synthesis. The G1 arrest appears to be responsible for the general inhibition of macromolecular synthesis in proliferating cells treated with 25-hydroxycholesterol. In contrast, the apparent coordinated inhibition of lipid synthesis is not a consequence of the G1 arrest but may in fact give rise to it. Sequential inhibition of lipid syntheses is also observed in cycling cells when the synthesis of choline-containing lipids is blocked by choline deprivation and is observed in association with G1 arrests caused by confluence or differentiation. In the nonproliferating cells, the syntheses of lipid and protein do not appear coupled.

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.

195 Lipid profiling of bovine oocytes matured with different stimulation of cyclic GMP synthesis by multiple reaction monitoring profiling

2020 ◽  
Vol 32 (2) ◽  
pp. 226
Author(s):  
L. Schefer ◽  
L. M. Naves ◽  
C. Ramires Ferreira ◽  
E. Pradebon da Silva ◽  
T. J. Sobreira ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Profile ◽  
Multiple Reaction Monitoring ◽  
Lipid Extraction ◽  
Protoporphyrin Ix ◽  
Lipid Classes ◽  
Control Group ◽  
Reaction Monitoring ◽  
Bovine Oocytes ◽  
Cgmp Synthesis

Intrafollicular lipid metabolism is very important for production species such as cattle. Lipids are essential substrates to produce energy during growth, maturation, and acquisition of high competence for the development of oocytes. However, the quantity and distribution of these lipids has been identified as responsible for hindering the process of cryopreservation of oocytes and embryos produced invitro. Previous studies have indicated that the cyclic (c) GMP pathway may be involved in the lipid metabolism of bovine cumulus-oocyte complexes (COC). The synthesis of this nucleotide can be activated through guanylate cyclases (soluble, sGC; or membrane, mGC). Therefore, the objective of this study was to investigate the lipid profile of bovine oocytes matured invitro (IVM) when stimulated by specific stimulators of sGC (protoporphyrin IX) and mGC (NPPB: peptide natriuretic type B). Pools of ovum pickup (OPU) oocytes were matured invitro for 24h in TCM-199 medium, with 15% bovine serum (BS), 0.5µgmL−1 of FSH, 5µgmL−1 of LH, 0.8mM L-glutamine, and 50µgmL−1 of gentamicin at 38.5°C and 10−5 M protoporphyrin IX or 10−6 M NPPB. The control group was matured without NPs or protoporphyrin IX. After IVM, cumulus cells (CC) were removed and oocytes (OO) collected, washed in 1:3 methanol:water (v/v) and frozen at −80°C. The lipid extraction of the samples was performed based on a standard protocol (Bligh and Dyer 1959 Can. J. Biochem. Physiol. 37, 911-917) but adapted for small samples. The samples were diluted and analysed on an Agilent 6410 QQQ (Agilent Technologies) mass spectrometer and analysed according to the multiple reaction monitoring (MRM) method described (de Lima et al. 2018 J. Mass. Spectrom. 53, 1247-52). Data for 3 replicates/group were normalized and then submitted to ANOVA statistical analysis, followed by Tukey test and principal components analysis, by Metaboanalyst 4.0, with an α-level of 5%. The results, representing the analysis of 164 lipids, showed that the lipid profile was not affected when we used the cGMP synthesis stimulators protoporphyrin IX and NPPB, maintaining the same profile of lipid classes in control and treatments. In addition, the quantitative values of the major lipid classes, sphingomyelin, triglycerides, and phospholipids (phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylinositol), were not altered in the treated groups. The values for each class (ng/oocyte) for control, NPPB, and protoporphyrin, respectively, were 0.89, 0.86, and 1.12 for sphingomyelin, 5.63, 5.66, and 6.90 for phosphatidylcholine, 7.34, 6.48, and 7.89 for triglycerides, 209.0, 244.0, and 207.4 for phosphatidylserine, 3.05, 3.0, and 2.35 for phosphatidylethanolamine, 3.40, 3.34, and 3.29 for phosphatidylglycerol, and 3.47, 3.52, and 3.51 for phosphatidylinositol (P&lt;0.05). Further, the amount of these lipids per class was not affected by cGMP synthesis when stimulated by protoporphyrin IX and NPPB, showing that the relationship of this pathway with lipid metabolism needs additional study.

scholarly journals Circadian lipid synthesis in brown fat maintains murine body temperature during chronic cold

2019 ◽  
Vol 116 (37) ◽  
pp. 18691-18699 ◽  
Author(s):  
Marine Adlanmerini ◽  
Bryce J. Carpenter ◽  
Jarrett R. Remsberg ◽  
Yann Aubert ◽  
Lindsey C. Peed ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Body Temperature ◽  
Cold Exposure ◽  
De Novo ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
High Amplitude ◽  
De Novo Lipogenesis ◽  
Brown Adipose ◽  
The Impact

Ambient temperature influences the molecular clock and lipid metabolism, but the impact of chronic cold exposure on circadian lipid metabolism in thermogenic brown adipose tissue (BAT) has not been studied. Here we show that during chronic cold exposure (1 wk at 4 °C), genes controlling de novo lipogenesis (DNL) includingSrebp1, the master transcriptional regulator of DNL, acquired high-amplitude circadian rhythms in thermogenic BAT. These conditions activated mechanistic target of rapamycin 1 (mTORC1), an inducer ofSrebp1expression, and engaged circadian transcriptional repressors REV-ERBα and β as rhythmic regulators ofSrebp1in BAT. SREBP was required in BAT for the thermogenic response to norepinephrine, and depletion of SREBP prevented maintenance of body temperature both during circadian cycles as well as during fasting of chronically cold mice. By contrast, deletion of REV-ERBα and β in BAT allowed mice to maintain their body temperature in chronic cold. Thus, the environmental challenge of prolonged noncircadian exposure to cold temperature induces circadian induction of SREBP1 that drives fuel synthesis in BAT and is necessary to maintain circadian body temperature during chronic cold exposure. The requirement for BAT fatty acid synthesis has broad implications for adaptation to cold.

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