Protein in culture and endogenous lipid interact with embryonic stages in vitro to alter calf birthweight after embryo vitrification and warming

2017 ◽  
Vol 29 (10) ◽  
pp. 1932 ◽  
Author(s):  
E. Gómez ◽  
S. Carrocera ◽  
S. Uzbekova ◽  
D. Martín ◽  
A. Murillo ◽  
...  
Keyword(s):  
Stress Responses ◽  
Regulatory Element ◽  
Pregnancy Rates ◽  
Hormone Sensitive Lipase ◽  
Expression Of Genes ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Hormone Sensitive

Short-term protein removal in vitro improves long-term blastocyst competence to survive vitrification. We investigated the mechanisms and effects underlying protein removal. Day-6 morulae and early blastocysts were cultured individually with and without protein for 24 h. Development and lipid content were analysed in expanded blastocysts derived from morulae (M-XB) and from early blastocysts (EB-XB). Expression of genes involved in lipid metabolism, stress responses and apoptosis was analysed in fresh and vitrified–warmed M-XB produced with and without protein. Pregnancy rates, birth rates and birthweight (BW) were recorded after transfer of embryos. Day-7 EB-XB production rates (with, 66.9 ± 6.2 and without, 68.8 ± 6.0 protein) were higher than M-XB rates (with, 21.4 ± 4.6 and without, 9.4 ± 4.6 protein; P < 0.005). EB-XB showed fewer lipids than M-XB (P = 0.03). In fresh M-XB, expression of sterol regulatory element binding protein (SREBP1) was lower with (4.1 ± 2.2) than without (13.6 ± 2.2) protein, contrary to results obtained for Patatin-like phospholipase domain containing 2, Hormone-sensitive lipase and Bcl-2–associated X protein (P < 0.05). Protein did not affect pregnancy rates and birth phenotypes (P > 0.05). However, BW was higher (P < 0.01) in calves born from vitrified M-XB (48.6 ± 3.4 kg) than from EB-XB (39.8 ± 2.9 kg). Such effects were more pronounced in females (P < 0.001). Calves from fresh embryos did not show BW differences. These results indicate that embryonic kinetics and vitrification impact birth phenotypes, at least in females. Alterations might involve exogenous protein and mobilisation of lipid stocks.

scholarly journals Sex-specific effects of in vitro fertilization on adult metabolic phenotypes and hepatic transcriptomic and proteomic pathways in mouse

2020 ◽  
Author(s):  
Laren Narapareddy ◽  
Eric A. Rhon-Calderon ◽  
Lisa A. Vrooman ◽  
Josue Baeza ◽  
Duy K. Nguyen ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Perinatal Outcomes ◽  
Vitro Fertilization ◽  
Specific Effects ◽  
Cholesterol Levels ◽  
Element Binding Protein ◽  
Fat Composition ◽  
Sterol Regulatory Element

AbstractAlthough in vitro fertilization (IVF) is associated with adverse perinatal outcomes, an increasing concern is the long-term health implications. We augmented our IVF mouse model to longitudinally investigate cardiometabolic outcomes in offspring from optimal neonatal litter sizes. We found that IVF-conceived females had higher body weight and cholesterol levels compared to naturally-conceived females, whereas IVF-conceived males had higher levels of triglycerides and insulin, and increased body fat composition. Through transcriptomics and proteomics of adult liver, we identified sexually-dimorphic dysregulation of the sterol regulatory element binding protein (SREBP) pathways that are associated with the sex-specfic phenotypes. We also found that global loss of DNA methylation in placenta was linked to higher cholesterol levels in IVF-conceived females. Our findings indicate that IVF procedures have long-lasting sex-specific effects on metabolic health of offspring and lay the foundation to utilize the placenta as a predictor of long-term outcomes.

The effect of long term under- and over-feeding on the expression of genes related to lipid metabolism in mammary tissue of sheep

2014 ◽  
Vol 82 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Eleni Tsiplakou ◽  
Emmanouil Flemetakis ◽  
Evangelia-Diamanto Kouri ◽  
Kyriaki Sotirakoglou ◽  
George Zervas
Keyword(s):  
Fatty Acid ◽  
Regulatory Element ◽  
Fatty Acid Synthetase ◽  
Hormone Sensitive Lipase ◽  
Mammary Tissue ◽  
Positive Energy ◽  
Peroxisome Proliferator ◽  
Nutritional Regulation ◽  
Expression Of Genes

Milk fatty acid (FA) synthesis by the mammary gland involves expression of a large number of genes whose nutritional regulation remains poorly defined. In this study, we examined the effect of long-term under- and over-feeding on the expression of genes (acetyl Co A carboxylase, ACC; fatty acid synthetase, FAS; lipoprotein lipase, LPL; stearoyl Co A desaturase, SCD; peroxisome proliferator activated receptor γ2, PPARγ2; sterol regulatory element binding protein-1, SREBP-1c; and hormone sensitive lipase, HSL) related to FA metabolism in sheep mammary tissue (MT). Twenty-four lactating sheep were divided into three homogenous sub-groups and fed the same ration in quantities covering 70% (underfeeding), 100% (control) and 130% (overfeeding) of their energy and crude protein requirements. The results showed a significant reduction of mRNA of ACC, FAS, LPL and SCD in the MT of underfed sheep, and a significant increase on the mRNA of LPL and SREBP-1c in the MT of overfed compared with the control respectively. In conclusion, the negative, compared to positive, energy balance in sheep down-regulates ACC, FAS, LPL, SCD, SREBP-1c and PPARγ2 expression in their MT which indicates that the decrease in nutrient availability may lead to lower rates of lipid synthesis.

scholarly journals A New Role for Sterol Regulatory Element Binding Protein 1 Transcription Factors in the Regulation of Muscle Mass and Muscle Cell Differentiation

2009 ◽  
Vol 30 (5) ◽  
pp. 1182-1198 ◽  
Author(s):  
Virginie Lecomte ◽  
Emmanuelle Meugnier ◽  
Vanessa Euthine ◽  
Christine Durand ◽  
Damien Freyssenet ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Muscle Mass ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Myogenic Program

ABSTRACT The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.

Sterol-regulatory-element-binding protein I c mediates insulin action on hepatic gene expression

2001 ◽  
Vol 29 (4) ◽  
pp. 547-552 ◽  
Author(s):  
P. Ferré ◽  
M. Foretz ◽  
D. Azzout-Marniche ◽  
D. Bécard ◽  
F. Foufelle
Keyword(s):  
Energy Homeostasis ◽  
Glucose Utilization ◽  
Binding Protein ◽  
Regulatory Element ◽  
Glucose Production ◽  
Pathological Conditions ◽  
Expression Of Genes ◽  
Adaptive Mechanisms ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Effects of insulin on the expression of liver-specific genes are part of the adaptive mechanisms aimed at maintaining energy homeostasis in mammals. When the diet is rich in carbohydrates, secreted insulin stimulates the expression of genes for enzymes involved in glucose utilization (glucokinase, L-type pyruvate kinase and lipogenic enzymes) and inhibits genes for enzymes involved in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which insulin controls the expression of these genes have been poorly understood. Recently, the transcription factor sterol-regulatory-element-binding protein 1c has been proposed as a key mediator of insulin transcriptional effects. Here we review the evidence that has led to this proposal and the consequences for our understanding of insulin effects in physiological or pathological conditions.

scholarly journals Functional antagonism between inhibitor of DNA binding (Id) and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP-1c) trans-factors for the regulation of fatty acid synthase promoter in adipocytes

1999 ◽  
Vol 344 (3) ◽  
pp. 873-880 ◽  
Author(s):  
Marthe MOLDES ◽  
Muriel BOIZARD ◽  
Xavier LE LIEPVRE ◽  
Bruno FÈVE ◽  
Isabelle DUGAIL ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Dna Binding ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Expression Vectors ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Inhibitor Of Dna Binding ◽  
Isolated Rat

We show that Id (inhibitor of DNA binding) 2 and Id3, dominant negative members of the helix-loop-helix (HLH) family, interact with the adipocyte determination and differentiation factor 1 (ADD1)/sterol regulatory element-binding protein (SREBP) 1c, a transcription factor of the basic HLH-leucine zipper family that controls the expression of several key genes of adipose metabolism. Gel mobility-shift assays performed with in vitro-translated ADD1, Id2 or Id3 proteins and a fatty acid synthase (FAS) promoter oligonucleotide showed evidence for a marked inhibition of the formation of DNA-ADD1 complexes by Id2 or Id3 proteins. Co-immunoprecipitation studies using in vitro-translated proteins demonstrated further the physical interaction of Id and ADD1/SREBP-1c proteins in the absence of DNA. Using the FAS gene as a model of an ADD1-regulated promoter in transiently transfected isolated rat adipocytes or mature 3T3-L1 adipocytes, a potent inhibition of the activity of the FAS-chloramphenicol acetyltransferase reporter gene was observed by overexpression of Id2 or Id3. Reciprocally, co-transfection of Id3 antisense and ADD1 expression vectors in preadipocytes potentiated the ADD1/SREBP-1c effect on the FAS promoter activity. Finally, in the non adipogenic NIH-3T3 cell line, most of the ADD1-mediated trans-activation of the FAS promoter was counteracted by co-transfection of Id2 or Id3 expression vectors. Previous studies have indicated Id gene expression to be down-regulated during adipogenesis [Moldes, Lasnier, Fève, Pairault and Djian (1997) Mol. Cell. Biol. 17, 1796-1804]. We here demonstrated that there was a dramatic rise of Id2 and Id3 mRNA levels when 3T3-L1 adipocytes or isolated rat fat cells were exposed to lipolytic and anti-lipogenic agents, forskolin and isoproterenol. Taken together, our data show that Id products are functionally involved in modulating ADD1/SREBP-1c transcriptional activity, and thus lipogenesis in adipocytes.

scholarly journals Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis-acting elements

2004 ◽  
Vol 385 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Lauren M. CAGEN ◽  
Xiong DENG ◽  
Henry G. WILCOX ◽  
Edwards A. PARK ◽  
Rajendra RAGHOW ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Rat Hepatocytes ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Cis Acting ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

The enhanced synthesis of fatty acids in the liver and adipose tissue in response to insulin is critically dependent on the transcription factor SREBP-1c (sterol-regulatory-element-binding protein 1c). Insulin increases the expression of the SREBP-1c gene in intact liver and in hepatocytes cultured in vitro. To learn the mechanism of this stimulation, we analysed the activation of the rat SREBP-1c promoter and its truncated or mutated congeners driving a luciferase reporter gene in transiently transfected rat hepatocytes. The rat SREBP-1c promoter contains binding sites for LXR (liver X receptor), Sp1, NF-Y (nuclear factor-Y) and SREBP itself. We have found that each of these sites is required for the full stimulatory response of the SREBP-1c promoter to insulin. Mutation of either the putative LXREs (LXR response elements) or the SRE (sterol response element) in the proximal SREBP-1c promoter reduced the stimulatory effect of insulin by about 50%. Insulin and the LXR agonist TO901317 increased the association of SREBP-1 with the SREBP-1c promoter. Ectopic expression of LXRα or SREBP-1c increased activity of the SREBP-1c promoter, and this effect is further enhanced by insulin. The Sp1 and NF-Y sites adjacent to the SRE are also required for full activation of the SREBP-1c promoter by insulin. We propose that the combined actions of the SRE, LXREs, Sp1 and NF-Y elements constitute an insulin-responsive cis-acting unit of the SREBP-1c gene in the liver.

scholarly journals Importin beta1 mediates the glucose-stimulated nuclear import of pancreatic and duodenal homeobox-1 in pancreatic islet beta-cells (MIN6)

2004 ◽  
Vol 378 (1) ◽  
pp. 219-227 ◽  
Author(s):  
Ghislaine GUILLEMAIN ◽  
Gabriela da SILVA XAVIER ◽  
Imran RAFIQ ◽  
Armelle LETURQUE ◽  
Guy A. RUTTER
Keyword(s):  
Nuclear Membrane ◽  
Nuclear Import ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Regulatory Element ◽  
Pancreatic Islet Beta Cells ◽  
Element Binding Protein ◽  
Elevated Glucose ◽  
Sterol Regulatory Element

The transcription factor PDX-1 (pancreatic and duodenal homeobox-1) is essential for pancreatic development and the maintainence of expression of islet β-cell-specific genes. In an previous study [Rafiq, Kennedy and Rutter (1998) J. Biol. Chem. 273, 23241–23247] we demonstrated that PDX-1 may be activated at elevated glucose concentrations by translocation from undefined binding sites in the cytosol and nuclear membrane into the nucleoplasm. In the present study, we show that PDX-1 interacts directly and specifically in vitro with the nuclear import receptor family member, importin β1, and that this interaction is mediated by the PDX-1 homeodomain (amino acids 146–206). Demonstrating the functional importance of the PDX-1–importin β1 interaction, microinjection of MIN6 β-cells with anti-(importin β1) antibodies blocked both the nuclear translocation of PDX-1, and the activation by glucose (30 mM versus 3 mM) of the pre-proinsulin promoter. However, treatment with extracts from pancreatic islets incubated at either low or high glucose concentrations had no impact on the ability of PDX-1 to interact with importin β1 in vitro. Furthermore, importin β1 also interacted with SREBP1c (sterol-regulatory-element-binding protein 1c) in vitro, and microinjection of importin β1 antibodies blocked the activation by glucose of SREBP1c target genes. Since the subcellular distribution of SREBP1c is unaffected by glucose, these findings suggest that a redistribution of importin β1 is unlikely to explain the glucose-stimulated nuclear uptake of PDX-1. Instead, we conclude that the uptake of PDX-1 into the nucleoplasm, as glucose concentrations increase, may be mediated by release of the factor both from sites of retention in the cytosol and from non-productive complexes with importin β1 at the nuclear membrane.

scholarly journals A Component Formula of Chinese Medicine for Hypercholesterolemia Based on Virtual Screening and Biology Network

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoqian Huo ◽  
Fang Lu ◽  
Liansheng Qiao ◽  
Gongyu Li ◽  
Yanling Zhang
Keyword(s):  
Chinese Medicine ◽  
Virtual Screening ◽  
Regulatory Element ◽  
Pharmacophore Model ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Coa Reductase

Hypercholesterolemia is a risk factor to atherosclerosis and coronary heart disease II. The abnormal rise of cholesterol in plasma is the main symptom. Cholesterol synthesis pathway is an important pathway of the origin of cholesterol, which is an essential pathway for the therapy of hypercholesterolemia. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), squalene synthase (SQS), and sterol regulatory element binding protein-2 (SREBP-2) are closely connected with the synthesis of cholesterol. The inhibition of these targets can reduce the cholesterol in plasma. This study aimed to build a component formula including three Traditional Chinese Medicines (TCM) components with the inhibition activity of these targets by using virtual screening and biological network. Structure-based pharmacophore models of HMG-CoA reductase and SQS and ligand-based pharmacophore model of SREBP-2 were constructed to screen the Traditional Chinese Medicine Database (TCMD). Molecular docking was used for further screening of components of HMG-CoA reductase and SQS. Then, metabolic network was constructed to elucidate the comprehensive interaction of three targets for lipid metabolism. Finally, three potential active compounds were obtained, which are poncimarin, hexahydrocurcumin, and forsythoside C. The source plants of the compounds were also taken into account, which should have known action of lowering hyperlipidemia. The lipid-lowering effect of hexahydrocurcumin was verified by experiment in vitro. The components that originated from TCMs with lipid-lowering efficacy made up a formula with a synergistic effect through the computer aid drug design methods. The research provides a fast and efficient method to build TCM component formula and it may inspire the study of the explanation of TCM formula mechanism.

scholarly journals Androgen Activation of the Sterol Regulatory Element-Binding Protein Pathway: Current Insights

2006 ◽  
Vol 20 (10) ◽  
pp. 2265-2277 ◽  
Author(s):  
Hannelore V. Heemers ◽  
Guido Verhoeven ◽  
Johannes V. Swinnen
Keyword(s):  
Androgen Receptor ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Response Elements ◽  
Cellular Effects ◽  
Complex Processes ◽  
Expression Of Genes ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Abstract The cellular effects of androgens are mediated by a cognate receptor, the androgen receptor. Typically, the androgen receptor is viewed to exert its activity by binding to androgen response elements located in or near the promoter region of target genes, thereby directly affecting the expression of these genes. However, increasing evidence indicates that androgens may also indirectly influence the expression of genes that do not contain androgen response elements by modulating the activity of secondary transcription factors, mediating the expression of growth factors acting in a paracrine or autocrine fashion, or by inducing changes in the production of other hormones. These indirect effects of androgens can induce cascade-like actions and may play an important role in more complex processes involving coordinated responses of genes, cells, and organs. Previously, our laboratory has identified and characterized a novel indirect mechanism of androgen action involving proteolytical activation of the key lipogenic transcription factor sterol regulatory element-binding protein (SREBP), resulting in the coordinate up-regulation of entire cellular lipogenic pathways. Interestingly, activation of SREBPs by androgens occurs not only under normal physiological conditions but has also been observed in a growing number of pathologies, and more in particular in the setting of steroid-regulated cancers, where increased lipogenesis has been shown to have remarkable diagnostic and prognostic potential and is considered a prime target for novel therapeutic approaches. This review aims to analyze current insights into the molecular mechanism(s) underlying androgen activation of the SREBP pathway and to ascertain the extent to which this phenomenon can be generalized to androgen-responsive cell systems.

scholarly journals Post-exercise Effects and Long-Term Training Adaptations of Hormone Sensitive Lipase Lipolysis Induced by High-Intensity Interval Training in Adipose Tissue of Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Yang Liu ◽  
Gaofang Dong ◽  
Xiaobo Zhao ◽  
Zerong Huang ◽  
Peng Li ◽  
...  
Keyword(s):  
Acute Exercise ◽  
Subcutaneous Fat ◽  
Interval Training ◽  
Hormone Sensitive Lipase ◽  
High Intensity Interval Training ◽  
Post Exercise ◽  
Hormone Sensitive ◽  
High Intensity Interval

Although studies have proven that high-intensity interval training (HIIT) shows a comparable effect to moderate-intensity continuous training (MICT) on reducing body fat, especially visceral fat, the mechanism is still unclear. Since MICT consumes more fat during exercise, the mechanism of HIIT weight loss may be related to post-exercise effects, long-term adaptive changes, and hormone sensitive lipase (HSL). The objective of this study was to compare the post-effects of acute exercise, long-term adaptive changes on HSL activity, and catecholamine-induced lipolysis between HIIT and MICT. Following a 14-week high-fat diet (HFD), obese female C57Bl/6 mice were divided into acute exercise groups (one time training, sacrificed at rest and 0, 1, and 12 h after exercise, n = 49), -L groups (12-week long-term training, 12-h fasting, n = 21), and -C groups (12-week training, primary adipocytes were isolated and stimulated by catecholamine in vitro, n = 18). MICT or HIIT treadmill protocols (running distance matched) were carried out during training. Comparison of acute exercise effects by two-way ANOVA showed no time × group interaction effect, however, a significant increase in HSL-Ser563 (at 0 and 1 h) and Ser660 phosphorylation (at 0, 1, and 12 h) in inguinal (subcutaneous) fat was only observed in HIIT mice (p &lt; 0.05 vs. rest), but not in MICT mice. The periuterine (visceral) fat HSL expression and phosphorylation of HIIT mice was similar to or lower than MICT mice. After long-term training, 12-h fasting significantly increased periuterine fat Ser563 phosphorylation in HIIT mice (p &lt; 0.05), but there was no change in MICT mice. Under stimulation of catecholamine in vitro, isolated primary adipocytes from periuterine fat of long-term HIIT mice showed a higher Ser563 increase than that found in MICT mice (p &lt; 0.05). The quantity of triglyceride (TG) lipid bonds (representing lipolysis level) was significantly lower after HIIT than MICT (p &lt; 0.05). The results indicate that (1) acute HIIT can induce an increase of HSL phosphorylation in subcutaneous fat lasting at least 12 h, implying longer post-exercise lipolysis than MICT and (2) long-time HIIT has a better effect on improving catecholamine resistance of visceral adipocytes caused by a HFD, which allows fat to be mobilized more easily when stimulated.

Sign in / Sign up

Export Citation Format

Share Document