scholarly journals Inhibition of Cardiomyogenesis in Embryocarcinoma Cells Induced by Long-Term High Level of Glucose

2016 ◽  
Vol 38 (5) ◽  
pp. 2041-2052
Author(s):  
Wen-Juan Li ◽  
Qian-Qian Guo ◽  
Lara Gharibeh ◽  
Rang Xu ◽  
Sun Chen ◽  
...  
Keyword(s):  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cardiac Progenitors ◽  
Normal Glucose ◽  
P19cl6 Cells ◽  
Heart Formation ◽  
High Level ◽  
The Impact

Background/Aims: Cardiac myocytes constitute the first differentiated cell type during mammalian heart formation with the ability to beat spontaneously and rhythmically. Hyperglycemia is a primary risk factor for cardiovascular disease in pre-gestational diabetes mellitus (PGDM). However, the impact that hyperglycemia has on cardiac progenitors or on precursors differentiation remains poorly understood. The aim of the present study is to investigate whether hyperglycemia affects cardiomyogenesis of embryocarcinoma cells. Methods: P19CL6 cells differentiation induced by 1% DMSO was evaluated under either normal glucose (5.6 mmol/L) or high level of glucose concentrations (20 mmol/L or 40 mmol/L). To investigate the effect of long-term high level of glucose on cardiomyocytes differentiation, sarcomeric α-actinin, peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), transcription factor GATA4 and Nkx2.5 were assessed by qRT-PCR analysis, western blot and immunofluorescence. Results: We observed that long-term high level of glucose markedly reduced P19CL6 cells differentiation into cardiomyocytes. The change in PGC-1α expression was consistent with changes in cardiac muscle myosin expression after exposure to 20 mmol/L or 40 mmol/L of glucose. On the other hand, the high level of glucose concentration profoundly decreased both GATA4 and Nkx2-5 expressions from day 6 to day 12 after differentiation, which was induced by 1% DMSO. Conclusion: Our results elucidate that the effect resulting from the long-term exposure of cardiac progenitors to high level of glucose is associated with decreased expression of GATA4 and Nkx2.5, providing a novel mechanism by which high glucose is able to affect cell differentiation.

scholarly journals The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6074
Author(s):  
Maciej Danielewski ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
Tomasz Sozański
Keyword(s):  
Transcription Factors ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Functions ◽  
The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

scholarly journals Zidovudine Impairs Adipogenic Differentiation through Inhibition of Clonal Expansion

2008 ◽  
Vol 52 (8) ◽  
pp. 2882-2889 ◽  
Author(s):  
Metodi V. Stankov ◽  
Reinhold E. Schmidt ◽  
Georg M. N. Behrens
Keyword(s):  
Adipogenic Differentiation ◽  
Clonal Expansion ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Accumulation ◽  
Thymidine Incorporation Assay ◽  
Human Preadipocytes ◽  
Incorporation Assay ◽  
The Impact

ABSTRACT Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 μM, 3 μM, 6 μM, and 180 μM), stavudine (d4T; 3 μM), or dideoxycytosine (ddC; 0.1 μM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [3H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C max) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C max did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

scholarly journals RT-PCR analysis of corticotroph-associated genes expression in carcinoid tumours in the ectopic-ACTH syndrome

2006 ◽  
Vol 154 (1) ◽  
pp. 159-166 ◽  
Author(s):  
M Messager ◽  
C Carrière ◽  
X Bertagna ◽  
Y de Keyzer
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Ectopic Acth Syndrome ◽  
Pcr Analysis ◽  
Peroxisome Proliferator ◽  
Rt Pcr ◽  
Ectopic Acth ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carcinoid Tumours ◽  
Transcription Factor Genes

Objective: ACTH is frequently produced in non-pituitary tumours, leading to the ectopic-ACTH syndrome, but the molecular mechanisms of its expression remain obscure. This study was aimed at understanding the transcription mechanisms of the ACTH-precursor gene in carcinoid tumours of the lung or thymus. Design: Transcripts coding for a series of corticotroph-associated transcription factor genes were detected, together with markers of the corticotroph phenotype. We studied a series of 41 carcinoid tumours including 15 with proven ectopic-ACTH syndrome. Methods: Specific RT-PCR reactions were designed for each gene including alternatively spliced isoforms. Results: The markers of the corticotroph phenotype were detected in all ACTH-positive tumours. Expression of the Tpit and Pitx1 genes were not restricted to ACTH-positive tumours but were also detected in many ACTH-negative carcinoids. Only a subset of ACTH-negative tumours expressed NAK-1/Nur77, and NeuroD1 expression was detected in <50% of the tumours regardless of their secretory status. The glucocorticoid receptor alpha was detected in every tumour in contrast to its beta isoform detectable in a few tumours only. Chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and peroxisome proliferator-activated receptor (PPAR) γ2 were expressed in 50% of the tumours of each group whereas PPARγ1 was expressed in almost every tumour. Conclusions: ACTH-positive carcinoids do not share a characteristic expression pattern of the corticotroph-associated transcription factor genes, suggesting that the transcriptional mechanisms of the ACTH-precursor gene differ from those in normal pituitary corticotrophs. Expression of Tpit and Pitx1 genes in most carcinoids suggests that some aspects of the pituitary corticotroph phenotype may belong to general carcinoid differentiation.

scholarly journals Maternal folic acid consumption during gestation and its long-term effects on offspring's liver: a systematic review

2017 ◽  
Vol 17 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Flavia Bittencourt Brasil ◽  
Luiz Henrique Amarante ◽  
Marcos Roberto de Oliveira
Keyword(s):  
Systematic Review ◽  
Folic Acid ◽  
Medical Society ◽  
Peroxisome Proliferator ◽  
Long Term Effects ◽  
High Intake ◽  
Peroxisome Proliferator Activated Receptor ◽  
Acid Consumption ◽  
Maternal Supplementation

Abstract Objectives: describing the effects of maternal supplementation with folic acid (FA) exclusively during gestation on offspring's liver at later stages in life. Supplementation with FA during gestation has been recommended by the medical society worldwide. The liver has a central role on the substances of metabolism and homeostasis and some studies have shown that a high intake of FA at other periods in life may cause hepatic damage. Methods: a systematic review through which the following databases were consulted: Medline, through platforms of Pubmed, Lilacs and Scielo. The research was performed by keywords such as: "Folic acid", "Gestation", "Rat", "Offspring" and "Liver". Articles which evaluate the effect of FA consumption during both gestation and lactation were excluded. Results: FA consumption avoids disorders on expression of peroxisome proliferator-activated receptor alpha (PPARα) and glucocorticoid receptor (GccR), its lack did not change enzyme activity of the male offspring's liver in adulthood. Supplementation with FA during gestation did not change iron hepatic levels or lipid composition, but had an antioxidant effect on it. Conclusions: supplementation with FA at recommended doses did not cause toxic effects and is very likely to avoid deleterious effects in the liver of the offspring regarding the epigenetic level.

scholarly journals Peroxisome Proliferator-Activated Receptor α (PPARα) Potentiates, whereas PPARγ Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3266-3276 ◽  
Author(s):  
Kim Ravnskjaer ◽  
Michael Boergesen ◽  
Blanca Rubi ◽  
Jan K. Larsen ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Stimulated Insulin Secretion

Abstract Fatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic β-cells. FA-coenzyme A esters have been shown to directly stimulate the secretion process, whereas long-term exposure of β-cells to FAs compromises glucose-stimulated insulin secretion (GSIS) by mechanisms unknown to date. It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2). In this study we show that adenoviral coexpression of PPARα and retinoid X receptor α (RXRα) in INS-1E β-cells synergistically and in a dose- and ligand-dependent manner increases the expression of known PPARα target genes and enhances FA uptake and β-oxidation. In contrast, ectopic expression of PPARγ/RXRα increases FA uptake and deposition as triacylglycerides. Although the expression of PPARα/RXRα leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient. Importantly, whereas expression of PPARγ/RXRα attenuates GSIS, the expression of PPARα/RXRα potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential. These results show a strong subtype specificity of the two PPAR subtypes α and γ on lipid partitioning and insulin secretion when systematically compared in a β-cell context.

scholarly journals Effects of 7°C environmental temperature acclimation during a 3-week training period

2020 ◽  
Vol 128 (4) ◽  
pp. 768-777
Author(s):  
Robert Shute ◽  
Katherine Marshall ◽  
Megan Opichka ◽  
Halee Schnitzler ◽  
Brent Ruby ◽  
...  
Keyword(s):  
Room Temperature ◽  
Environmental Temperature ◽  
Cellular Signaling ◽  
Temperature Acclimation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Training Adaptations ◽  
Before And After ◽  
The Impact ◽  
Environmental Temperatures

Cold environmental temperatures during exercise and recovery alter the acute response to cellular signaling and training adaptations. Approximately 3 wk is required for cold temperature acclimation to occur. To determine the impact of cold environmental temperature on training adaptations, fitness measurements, and aerobic performance, two groups of 12 untrained male subjects completed 1 h of cycling in 16 temperature acclimation sessions in either a 7°C or 20°C environmental temperature. Fitness assessments before and after acclimation occurred at standard room temperature. Muscle biopsies were taken from the vastus lateralis muscle before and after training to assess molecular markers related to mitochondrial development. Peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1α) mRNA was higher in 7°C than in 20°C in response to acute exercise before training ( P = 0.012) but not after training ( P = 0.813). PGC-1α mRNA was lower after training ( P < 0.001). BNIP3 was lower after training in the 7°C than in the 20°C group ( P = 0.017) but not before training ( P = 0.549). No other differences occurred between temperature groups in VEGF, ERRα, NRF1, NRF2, TFAM, PINK1, Parkin, or BNIP3L mRNAs ( P > 0.05). PGC-1α protein and mtDNA were not different before training, after training, or between temperatures ( P > 0.05). Cycling power increased during the daily training ( P < 0.001) but was not different between temperatures ( P = 0.169). V̇o2peak increased with training ( P < 0.001) but was not different between temperature groups ( P = 0.460). These data indicate that a 3-wk period of acclimation/training in cold environmental temperatures alters PGC-1α gene expression acutely but this difference is not manifested in a greater increase in V̇o2peak and is dissipated as acclimation takes place. NEW & NOTEWORTHY This study examines the adaptive response of cellular signaling during exercise in cold environmental temperatures. We demonstrate that peroxisome proliferator-activated receptor-γ coactivator 1α mRNA is different between cold and room temperature environments before training but after training this difference no longer exists. This initial difference in transcriptional response between temperatures does not lead to differences in performance measures or increases in protein or mitochondria.

scholarly journals Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies

2019 ◽  
Vol 20 (11) ◽  
pp. 2675 ◽  
Author(s):  
Nicholas Wilson ◽  
Robert Steadman ◽  
Ilaria Muller ◽  
Mohd Draman ◽  
D. Aled Rees ◽  
...  
Keyword(s):  
Stem Cell Differentiation ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Synthesis Inhibitor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inhibitory Role ◽  
The Impact

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity.

Impact of α-lipoic acid on liver peroxisome proliferator-activated receptor-α, vascular remodeling, and oxidative stress in insulin-resistant rats

2011 ◽  
Vol 89 (10) ◽  
pp. 743-751 ◽  
Author(s):  
Adil El Midaoui ◽  
Calin Lungu ◽  
Hui Wang ◽  
Lingyun Wu ◽  
Caroline Robillard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipoic Acid ◽  
Tap Water ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Resistant ◽  
Plasma Ffa ◽  
The Impact

This study sought to determine the impact of α-lipoic acid (LA) on superoxide anion (O2•–) production and peroxisome proliferator-activated receptor-α (PPARα) expression in liver tissue, plasma free fatty acids (FFA), and aortic remodeling in a rat model of insulin resistance. Sprague–Dawley rats (50–75 g) were given either tap water or a drinking solution containing 10% D-glucose for 14 weeks, combined with a diet with or without LA supplement. O2•– production was measured by lucigenin chemiluminescence, and PPAR-α expression by Western blotting. Cross-sectional area (CSA) of the aortic media and lumen and number of smooth muscle cells (SMC) were determined histologically. Glucose increased systolic blood pressure (SBP), plasma levels of glucose and insulin, and insulin resistance (HOMA index). All of these effects were attenuated by LA. Whereas glucose had no effect on liver PPAR-α protein level, it decreased plasma FFA. LA decreased the aortic and liver O2•– production, body weight, and plasma FFA levels in control and glucose-treated rats. Liver PPAR-α protein levels were increased by LA, and negatively correlated with plasma FFA. Medial CSA was reduced in all glucose-treated rats, and positively correlated with plasma FFA but not with SBP or aortic O2•– production. Glucose also reduced aortic lumen area, so that the media-to-lumen ratio remained unchanged. The ability of LA to lower plasma FFA appears to be mediated, in part, by increased hepatic PPAR-α expression, which may positively affect insulin resistance. Glucose-fed rats may serve as a unique model of aortic atrophic remodeling in hypertension and early metabolic syndrome.

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