scholarly journals Paternal High Fat Diet and Exercise Regulate Sperm miRNA to Alter Placental Inflammation and Nutrient Transporter Expression in a Sex-Dependent Manner

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1024-1024
Author(s):  
Kate Larson ◽  
Amy Bundy ◽  
James Roemmich
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Mirna Expression ◽  
Placental Tissue ◽  
Tissue Growth ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
High Fat ◽  
Diet And Exercise ◽  
Nutrient Transporter

Abstract Objectives We have shown that male offspring (F1) of fathers (F0) fed a high fat (HF) diet and exercised had greater skeletal muscle insulin signaling and reduced T2DM risk compared to fathers fed HF diet and remain sedentary. The current study extends this work by hypothesizing that F0 HF diet and exercise regulate F1 T2DM risk by early alterations in epigenetics of placental tissue growth via changes in sperm miRNA expression. Methods To test these hypotheses, three-week old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or a HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF diet fed dams. F0 sperm and placental tissue samples were collected to determine changes in placental and fetal weights, placental gene expression, and F0 sperm miRNA expression. Results F0 sperm miRNA 193b expression was decreased while miRNA 204 was increased by paternal exercise. Protein expression of di-methylated histone 3 lysine 9 was decreased with F0 HF diet. Placental and fetal tissue weights were decreased by F0 HF diet in F1 males while no changes in the F1 females. Placental proinflammatory cytokine mRNA expression, including IL-1 beta and TNF-alpha, was reduced by paternal exercise while nutrient transporter mRNA expression was decreased by paternal HF diet only in the placentae of F1 females. Treatment of primary placental cell with miRNA 193 inhibited TNF-alpha mRNA expression. In addition, treatment of the same cells with TNF-alpha increased SLC6a19. Moreover, paternal exercise increased body weight at weaning in a female offspring. Conclusions These results demonstrate that placental tissue weight, placental nutrient transporter gene expression and fetal weights are altered by paternal exercise while placental inflammatory gene expression are influenced by paternal exercise in offspring in a sex-specific manner. Funding Sources This work was supported by USDA ARS Project #3062–51,000-054–00D.

scholarly journals Isoproterenol is a positive regulator of the suppressor of cytokine signaling-3 gene expression in 3T3-L1 adipocytes

2002 ◽  
Vol 175 (3) ◽  
pp. 727-733 ◽  
Author(s):  
M Fasshauer ◽  
J Klein ◽  
U Lossner ◽  
R Paschke
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Mrna Expression ◽  
Adenylyl Cyclase ◽  
Insulin Signaling ◽  
Tnf Alpha ◽  
Cytokine Signaling ◽  
Dependent Manner ◽  
Suppressor Of Cytokine Signaling ◽  
Beta Adrenergic

SOCS (suppressor of cytokine signaling)-3 has recently been shown to be an insulin- and tumor necrosis factor (TNF)-alpha-induced negative regulator of insulin signaling. To further clarify a potential involvement of SOCS-3 in the development of insulin resistance, we measured differentiation-dependent SOCS-3 mRNA expression in 3T3-L1 adipocytes and studied its regulation by various hormones known to impair insulin signaling using quantitative real-time RT-PCR. There was a differentiation-dependent downregulation of SOCS-3 mRNA by 50% over the 9 day adipocyte differentiation course. Interestingly, besides insulin and TNF-alpha, chronic treatment of differentiated 3T3-L1 cells with 10 microM isoproterenol for 16 h stimulated SOCS-3 gene expression by about 3.5-fold. Furthermore, isoproterenol stimulated SOCS-3 mRNA expression in a dose-dependent manner with significant activation detectable at concentrations as low as 10 nM isoproterenol. Moreover, a strong 27- and 47-fold activation of SOCS-3 mRNA expression could be seen after 1 h of isoproterenol and GH treatment respectively. The stimulatory effect of isoproterenol could be almost completely reversed by pretreatment of 3T3-L1 cells with the beta-adrenergic antagonist propranolol. Finally, isoproterenol's action could be mimicked by stimulation of G(S)-proteins with cholera toxin and of adenylyl cyclase with forskolin and dibutyryl cAMP. Taken together, our results demonstrate a differentiation-dependent downregulation of SOCS-3 in adipocytes and suggest that SOCS-3 gene expression is stimulated by beta-adrenergic agents via activation of a G(S)-protein-adenylyl cyclase-dependent pathway. As SOCS-3 is a novel inhibitor of insulin signaling, the data support a possible role of this protein as a selectively regulated mediator of catecholamine-induced insulin resistance.

scholarly journals The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

1998 ◽  
Vol 158 (3) ◽  
pp. 351-358 ◽  
Author(s):  
RA Ajjan ◽  
PF Watson ◽  
C Findlay ◽  
RA Metcalfe ◽  
M Crisp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Ex Vivo ◽  
Tnf Alpha ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Mrna Tissue Distribution ◽  
Nis Gene ◽  
Rat Thyroid

Iodide concentration by the thyroid gland, an essential step for thyroid hormone synthesis, is mediated by the Na+/I- symporter (NIS). To identify factors that may regulate this process, we have studied NIS gene expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. Increasing concentrations of bovine TSH (0.1, 1, 10, 50 and 100 mU/l), with or without tumour necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma) or interleukin-1 alpha (IL-1 alpha) were added to FRTL-5 cells previously deprived of TSH for a minimum of 5 days. RNA was extracted and samples were studied for NIS expression. TSH enhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0.1 mU/l, reaching a peak at 50 mU/l, an effect detected after 6 h of stimulation, but not in the first 2 h. Both TNF alpha and, to a lesser extent, IL-1 alpha inhibited basal and TSH-induced NIS expression. High concentrations of IFN gamma also downregulated TSH-stimulated NIS mRNA expression. Using the same technique, we also investigated NIS mRNA tissue distribution in two male and one female Wistar rats. High levels of NIS expression were detected in the thyroid, stomach, and mammary gland, lower levels were found in the intestine, adipose tissue and liver, borderline levels were expressed in the salivary gland, and no expression was detected in the kidneys. In summary, we have shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples.

scholarly journals Temporal analysis of mRNA and miRNA expression in transgenic mice overexpressing Arg- and Gly389 polymorphic variants of the β1-adrenergic receptor

2011 ◽  
Vol 43 (23) ◽  
pp. 1294-1306 ◽  
Author(s):  
Karen Dockstader ◽  
Karin Nunley ◽  
Anis Karimpour-Fard ◽  
Allen Medway ◽  
Penny Nelson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Disease Progression ◽  
Mirna Expression ◽  
Adrenergic Receptor ◽  
Transgenic Animals ◽  
Temporal Analysis ◽  
Specific Pattern ◽  
Dependent Manner

Several studies in humans or transgenic animals have reported that the 389 Arg or Gly polymorphic variation of the β1-adrenergic receptor (AR) is associated with differential responses to beta-blocker therapy and/or myocardial disease progression. Analysis of changes in gene expression is an important means of defining molecular differences associated with structural or functional phenotypic variations. To determine if structural and functional myocardial phenotypic differences between β1389 Arg vs. Gly transgenic overexpressors are associated with qualitative and/or quantitative differences in gene expression, a comprehensive analysis of mRNAs and miRNAs expressed in the hearts of 3 and 6–8 mo old β1-Arg389 and β1-Gly389 overexpressor transgenic mice was performed. Changes in mRNA and miRNA expression were analyzed by arrays and partially confirmed by RT-qPCR. Bioinformatic analysis demonstrated that several genes, including those involved in PKA and CaMK signaling pathways, are regulated in a temporal- or phenotype-specific manner. Furthermore, expression signature analyses indicated that miRNAs have the potential to target expression of a number of genes involved in multiple cardiomyopathy-related pathways, and changes in miRNA expression can precede the onset of disease. Differences in gene expression between β1-Arg389 and β1-Gly389 transgenic mice are largely quantitative rather than qualitative and are associated with the development of cardiomyopathy in a time-dependent manner. Chronic β1-AR overdrive results in increased expression of components of the CaMK pathway, with correspondingly decreased levels of components of the PKA pathway. Based on the temporal and genotype-specific pattern of miRNA expression, miRNAs are likely to be important predictors of disease states, especially when miRNA expression is paired with mRNA expression, and that miRNA/mRNA expression signatures have the potential to be useful in determining the underlying risk associated with cardiac disease progression.

Abstract 316: A Potential Mechanism Involving mTOR For The Expression Of CTGF In Agonist-stimulated Adult Cardiomyocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kamala P Sundararaj ◽  
Sundaravadivel Balasubramanian ◽  
Dorea Pleasant ◽  
Dhandapani Kuppuswamy
Keyword(s):  
Mrna Expression ◽  
Wound Repair ◽  
Cardiac Fibrosis ◽  
Interstitial Fibrosis ◽  
Treatment Options ◽  
Tissue Growth ◽  
Dependent Manner ◽  
Potential Mechanism ◽  
Wall Stiffness ◽  
Wide Range

Cardiac hypertrophy ensues as a response to multiple stimuli, such as mechanical stress, neurohumoral activation, growth factors and cytokines. Connective Tissue Growth Factor (CTGF), a potent fibrogenic cytokine, regulates a wide range of biological functions including ECM deposition, wound repair, angiogenesis, migration, differentiation, survival and proliferation. While CTGF overexpression in fibroblasts has been shown to be responsible for fibrosis in various organs, controversy exists about the source of CTGF. Since interstitial fibrosis contributes to ventricular wall stiffness and impairs diastolic function, understating how key factors such as CTGF are expressed and released for the genesis of fibrosis in the hypertrophying heart is important to develop new treatment options. To this end, we explored the signaling pathway(s) involved in the phenylephrine (PE), a hypertrophic agonist, induced expression of CTGF by cardiomyocytes (CMs). Since mammalian target of rapamycin (mTOR) is reported to regulate PE-induced hypertrophic signaling, we hypothesize that mTOR plays a role in PE induced CTGF expression in CMs. To test if CMs produce CTGF, we treated adult feline CMs with phenylephrine. PE stimulated CTGF mRNA expression in a dose and time dependent manner. mTOR forms two distinct complexes, mTORC1 and mTORC2. Whereas both complexes are sensitive to a pharmacological inhibitor Torin1, only mTORC1 is sensitive to Rapamycin inhibition. Our results indicate that PE stimulated CTGF expression could be substantially enhanced by torin1 pretreatment of CMs. Moreover, shRNA mediated silencing of Rictor in CMs, one of the components of mTORC2, significantly augmented the PE induced CTGF mRNA expression. But mTORC1 inhibition using Rapamycin or activation of its downstream target S6K1 using Rapamycin resistant S6K1 adenovirus had no impact in PE -stimulated CTGF expression. The same trend was also observed in the level of secreted CTGF. In conclusion, these results strongly indicate that mTORC2 plays a repressive role in CTGF mRNA expression in adult CMs, and that the loss of such repression in PO myocardium might be a potential mechanism for the onset of cardiac fibrosis in hypertrophying myocardium.

Respiratory syncytial virus increases IL-8 gene expression and protein release in A549 cells

1995 ◽  
Vol 269 (6) ◽  
pp. L865-L872 ◽  
Author(s):  
M. A. Fiedler ◽  
K. Wernke-Dollries ◽  
J. M. Stark
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Viral Replication ◽  
Mrna Expression ◽  
A549 Cells ◽  
Protein Release ◽  
Tnf Alpha ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Syncytial Virus

The mechanism of respiratory syncytial virus (RSV)-induced inflammation in the airways of infants and children is not fully understood. We hypothesized that RSV directly induces interleukin (IL)-8 gene expression in airway epithelial cells, independent of IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) production. Exposure of A549 cells (an airway epithelial cell line) to RSV resulted in increased IL-8 mRNA expression and IL-8 protein release from the cells as early as 2 h after treatment. Neither IL-1 beta nor TNF-alpha (mRNA or protein) were detected. Viral replication was not necessary for the effects of RSV on IL-8 mRNA expression and protein release early in the infectious process. However, sustained levels of increased IL-8 production required RSV replication. A dose-response relationship was observed between the multiplicity of infection and IL-8 production with both active and nonreplicative RSV at the 2-h time point. Both active RSV and nonreplicative RSV increased the transcriptional activity of the 1.6-kb 5' flanking region of the IL-8 gene. Neither active RSV nor nonreplicative RSV increased the stability of the IL-8 mRNA in A549 cells. We conclude that RSV increases IL-8 gene expression in A549 cells in a biphasic pattern independent of viral replication early (2 h) but dependent on viral replication late (24 h).

scholarly journals Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation

2001 ◽  
pp. 187-192 ◽  
Author(s):  
E Schoof ◽  
M Girstl ◽  
W Frobenius ◽  
M Kirschbaum ◽  
R Repp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Placental Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Normal Pregnancy ◽  
Premature Babies ◽  
Gene Level ◽  
Human Placental Tissue ◽  
Human Placental Cells

BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.

scholarly journals Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Calcitonin Gene-Related Peptide (CGRP)-I and Procalcitonin (Pro-CT) Production in Human Adipocytes

2011 ◽  
Vol 96 (2) ◽  
pp. E297-E303 ◽  
Author(s):  
Katharina Timper ◽  
Jean Grisouard ◽  
Tanja Radimerski ◽  
Kaethi Dembinski ◽  
Ralph Peterli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Obese Patients ◽  
Human Adipocytes ◽  
High Fat ◽  
Metabolic Complications ◽  
Related Peptide ◽  
Fat Meal

abstract Context: Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet. Objective: The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients. Design and Participants: Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed. Results: Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P &lt; 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P &lt; 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P &lt; 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P &lt; 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P &lt; 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients. Conclusion: GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations.

scholarly journals Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis.

1997 ◽  
Vol 8 (2) ◽  
pp. 214-222 ◽  
Author(s):  
W Zhou ◽  
P A Andrews ◽  
Y Wang ◽  
J Wolff ◽  
J Pratt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Membrane Attack Complex ◽  
Classical Pathway ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Renal Epithelium ◽  
Renal Tubular Epithelium ◽  
Heymann Nephritis

Passive Heymann nephritis (PHN) is a complement-dependent model of immune complex glomerulonephritis. This study investigated the contribution of local complement synthesis by studying gene expression of the classical pathway component C4 in relation to the site of the tissue injury and the development of proteinuria induced by the pathogenic antibody (sheep anti-GP330). This study, using in situ hybridization, found that C4 mRNA expression was increased in the glomerular epithelium and the proximal renal tubular epithelium in a distribution similar to that of the targeted GP330 antigen. The total cortical C4 mRNA expression assessed by semiquantitative polymerase chain reaction (PCR) increased in a time-dependent manner (P < 0.05), coincident with the onset and progression of proteinuria, and peaking 11 to 14 days after the induction of the disease. These data suggest a link, in place and time, between local complement gene expression and glomerular barrier dysfunction induced by anti-GP330. It is postulated that increased epithelial synthesis of C4 stimulated by the engagement of GP330 enhances the formation of the membrane attack complex of complement through its classical pathway, and, hence, the formation of complement-mediated injury.

scholarly journals Combination effects of a fatty diet and exercise on the depressive state and cardioprotection in apolipoprotein E knockout mice with a change in RCAN1 expression

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096401
Author(s):  
Wang Shuo ◽  
Haicong Li ◽  
Nishijo Muneko ◽  
Nishino Yoshikazu ◽  
Nobuo Kato ◽  
...  
Keyword(s):  
Body Weight ◽  
Apolipoprotein E ◽  
Mrna Expression ◽  
High Fat Diet ◽  
Heart Weight ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
Apolipoprotein E Knockout Mice ◽  
Diet And Exercise

Objective Regulator of calcineurin 1 (RCAN1) controls plasticity of the nervous system and depressive conditions by regulating brain-derived neurotropic factor (BDNF) and plays a crucial role in neural and cardiac pathways. The apolipoprotein E gene ( ApoE) is a robust risk factor for progression of Alzheimer’s disease. A fatty diet is considered detrimental for metabolic disorders, such as obesity and cardiovascular diseases. Methods We examined the neuronal and cardiac protective roles of RCAN1 in ApoE−/− mice that were fed a high- or low-fat diet with and without voluntary movement for 3 months. Organ weights, laboratory data, histology, RNA expression, and behavior were examined. Results A high-fat diet with exercise improved depressive function, as examined by the forced swimming test, and RCAN1 mRNA expression was induced in the hippocampus. A low-fat diet with exercise resulted in a reduced body weight, higher heart weight/body weight ratio, and lower circulating triglyceride levels compared with a low-fat diet without exercise. RCAN1 mRNA expression was increased in cardiomyocytes in ApoE−/− mice. Conclusions The combination of a high-fat diet and exercise might reduce depressive function, whereas a low-fat diet with exercise leads to cardioprotection. Induction of RCAN1 expression might affect neuroplasticity and cardiac function.

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