scholarly journals Persistent Epigenetic Reprogramming of Sweet Taste by Diet

2020 ◽  
Author(s):  
Anoumid Vaziri ◽  
Morteza Khabiri ◽  
Brendan T. Genaw ◽  
Christina E. May ◽  
Peter L. Freddolino ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Sweet Taste ◽  
Taste Perception ◽  
Epigenetic Mechanism ◽  
High Sugar ◽  
Epigenetic Regulator ◽  
Transcriptional Changes ◽  
Gustatory Neurons

AbstractDiets rich in sugar, salt, and fat alter taste perception and food intake, leading to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons of D. melanogaster flies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Importantly, half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.

scholarly journals Persistent epigenetic reprogramming of sweet taste by diet

2020 ◽  
Vol 6 (46) ◽  
pp. eabc8492
Author(s):  
Anoumid Vaziri ◽  
Morteza Khabiri ◽  
Brendan T. Genaw ◽  
Christina E. May ◽  
Peter L. Freddolino ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Sweet Taste ◽  
Taste Perception ◽  
Epigenetic Mechanism ◽  
High Sugar ◽  
Epigenetic Regulator ◽  
Transcriptional Changes ◽  
Gustatory Neurons

Diets rich in sugar, salt, and fat alter taste perception and food preference, contributing to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here, we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons of Drosophila melanogaster flies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.

scholarly journals Mutant p53 Drives Clonal Hematopoiesis through Modulating Epigenetic Pathway

2019 ◽  
Author(s):  
Sisi Chen ◽  
Qiang Wang ◽  
Hao Yu ◽  
Maegan L. Capitano ◽  
Sasidhar Vemula ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Epigenetic Mechanism ◽  
Mutant P53 ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Induced Stress ◽  
Epigenetic Regulator ◽  
Radiation Induced

AbstractClonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. We discovered that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Further, genetic and pharmacological inhibition of EZH2 decrease the repopulating potential of p53 mutant HSPCs. Thus, we have uncovered an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations.

scholarly journals Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sisi Chen ◽  
Qiang Wang ◽  
Hao Yu ◽  
Maegan L. Capitano ◽  
Sasidhar Vemula ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Epigenetic Mechanism ◽  
Mutant P53 ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Induced Stress ◽  
Epigenetic Regulator ◽  
Radiation Induced

AbstractClonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Here we discover that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Furthermore, genetic and pharmacological inhibition of EZH2 decreases the repopulating potential of p53 mutant HSPCs. Thus, we uncover an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations.

scholarly journals Biophysical and functional characterization of the human TAS1R2 sweet taste receptor overexpressed in a HEK293S inducible cell line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christine Belloir ◽  
Marine Brulé ◽  
Lucie Tornier ◽  
Fabrice Neiers ◽  
Loïc Briand
Keyword(s):  
Cell Line ◽  
Molecular Mechanisms ◽  
Transmembrane Domain ◽  
Functional Characterization ◽  
Taste Receptor ◽  
Spectroscopic Studies ◽  
Sweet Taste ◽  
Taste Perception ◽  
Size Exclusion ◽  
High Potency

AbstractSweet taste perception is mediated by a heterodimeric receptor formed by the assembly of the TAS1R2 and TAS1R3 subunits. TAS1R2 and TAS1R3 are class C G-protein-coupled receptors whose members share a common topology, including a large extracellular N-terminal domain (NTD) linked to a seven transmembrane domain (TMD) by a cysteine-rich domain. TAS1R2-NTD contains the primary binding site for sweet compounds, including natural sugars and high-potency sweeteners, whereas the TAS1R2-TMD has been shown to bind a limited number of sweet tasting compounds. To understand the molecular mechanisms governing receptor–ligand interactions, we overexpressed the human TAS1R2 (hTAS1R2) in a stable tetracycline-inducible HEK293S cell line and purified the detergent-solubilized receptor. Circular dichroism spectroscopic studies revealed that hTAS1R2 was properly folded with evidence of secondary structures. Using size exclusion chromatography coupled to light scattering, we found that the hTAS1R2 subunit is a dimer. Ligand binding properties were quantified by intrinsic tryptophan fluorescence. Due to technical limitations, natural sugars have not been tested. However, we showed that hTAS1R2 is capable of binding high potency sweeteners with Kd values that are in agreement with physiological detection. This study offers a new experimental strategy to identify new sweeteners or taste modulators that act on the hTAS1R2 and is a prerequisite for structural query and biophysical studies.

scholarly journals Differences in Sweet Taste Perception and Its Association with the Streptococcus mutans Cariogenic Profile in Preschool Children with Caries

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2592
Author(s):  
Anna Jurczak ◽  
Małgorzata Jamka-Kasprzyk ◽  
Zuzanna Bębenek ◽  
Małgorzata Staszczyk ◽  
Paweł Jagielski ◽  
...  
Keyword(s):  
Preschool Children ◽  
Sweet Taste ◽  
Assessment System ◽  
Taste Perception ◽  
Taste Preferences ◽  
Microbiological Analysis ◽  
Strong Positive Correlation ◽  
Chi Square ◽  
Icdas Ii ◽  
Chi Square Test

The aim of the study was to verify the hypothesis about differences in sweet taste perception in the group of preschool children with and without caries, and to determine its relationship with cariogenic microbiota and the frequency of sweets consumption in children. The study group included of 63 children aged 2–6 years: 32 with caries and 31 without caries. The study consisted of collecting questionnaire data and assessment of dental status using the decayed, missing, filled in primary teeth index (dmft) and the International Caries Detection and Assessment System (ICDAS II). The evaluation of sweet taste perception was carried out using a specific method that simultaneously assessed the level of taste preferences and the sensitivity threshold for a given taste. The microbiological analysis consisted of the assessment of the quantitative and qualitative compositions of the oral microbiota of the examined children. The sweet taste perception of children with caries was characterized by a lower susceptibility to sucrose (the preferred sucrose solution concentration was >4 g/L) compared to children without caries (in the range ≤ 4 g/L, p = 0.0015, chi-square test). A similar relationship was also observed for frequent snacking between meals (p = 0.0038, chi-square test). The analysis of studied variables showed the existence of a strong positive correlation between the perception of sweet taste and the occurrence and intensity of the cariogenic process (p = 0.007 for dmft; and p = 0.012 for ICDAS II), as well as the frequency of consuming sweets (p ≤ 0.001 for frequent and repeated consumption of sweets during the day, Spearman test) in children with caries. Additionally, children with an elevated sucrose taste threshold were more than 10-times more likely to develop S. mutans presence (OR = 10.21; 95% CI 3.11–33.44). The results of this study suggest the future use of taste preferences in children as a diagnostic tool for the early detection of increased susceptibility to caries through microbial dysbiosis towards specific species of microorganisms.

scholarly journals Orosensory Perception of Fat/Sweet Stimuli and Appetite-Regulating Peptides before and after Sleeve Gastrectomy or Gastric Bypass in Adult Women with Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 878
Author(s):  
Arnaud Bernard ◽  
Johanne Le Beyec-Le Bihan ◽  
Loredana Radoi ◽  
Muriel Coupaye ◽  
Ouidad Sami ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Gastric Bypass ◽  
Sleeve Gastrectomy ◽  
Gut Hormones ◽  
Sweet Taste ◽  
Taste Perception ◽  
Taste Sensitivity ◽  
Adult Women ◽  
Before And After ◽  
The Impact

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m2) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.

scholarly journals PCGF1 promotes epigenetic activation of stemness markers and colorectal cancer stem cell enrichment

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Guangyu Ji ◽  
Wenjuan Zhou ◽  
Jingyi Du ◽  
Juan Zhou ◽  
Dong Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tumour Progression ◽  
Stem Cell Markers ◽  
Epigenetic Regulator ◽  
Cell Enrichment ◽  
Histone Trimethylation

AbstractColorectal cancer (CRC) stem cells are resistant to cancer therapy and are therefore responsible for tumour progression after conventional therapy fails. However, the molecular mechanisms underlying the maintenance of stemness are poorly understood. In this study, we identified PCGF1 as a crucial epigenetic regulator that sustains the stem cell-like phenotype of CRC. PCGF1 expression was increased in CRC and was significantly correlated with cancer progression and poor prognosis in CRC patients. PCGF1 knockdown inhibited CRC stem cell proliferation and CRC stem cell enrichment. Importantly, PCGF1 silencing impaired tumour growth in vivo. Mechanistically, PCGF1 bound to the promoters of CRC stem cell markers and activated their transcription by increasing the H3K4 histone trimethylation (H3K4me3) marks and decreasing the H3K27 histone trimethylation (H3K27me3) marks on their promoters by increasing expression of the H3K4me3 methyltransferase KMT2A and the H3K27me3 demethylase KDM6A. Our findings suggest that PCGF1 is a potential therapeutic target for CRC treatment.

scholarly journals RNA–Binding Protein HuD as a Versatile Factor in Neuronal and Non–Neuronal Systems

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 361
Author(s):  
Myeongwoo Jung ◽  
Eun-Kyung Lee
Keyword(s):  
Gene Expression ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Novel Treatments ◽  
Target Mrnas ◽  
Neuronal Systems

HuD (also known as ELAVL4) is an RNA–binding protein belonging to the human antigen (Hu) family that regulates stability, translation, splicing, and adenylation of target mRNAs. Unlike ubiquitously distributed HuR, HuD is only expressed in certain types of tissues, mainly in neuronal systems. Numerous studies have shown that HuD plays essential roles in neuronal development, differentiation, neurogenesis, dendritic maturation, neural plasticity, and synaptic transmission by regulating the metabolism of target mRNAs. However, growing evidence suggests that HuD also functions as a pivotal regulator of gene expression in non–neuronal systems and its malfunction is implicated in disease pathogenesis. Comprehensive knowledge of HuD expression, abundance, molecular targets, and regulatory mechanisms will broaden our understanding of its role as a versatile regulator of gene expression, thus enabling novel treatments for diseases with aberrant HuD expression. This review focuses on recent advances investigating the emerging role of HuD, its molecular mechanisms of target gene regulation, and its disease relevance in both neuronal and non–neuronal systems.

Measures of anhedonia and hedonic responses to sucrose in depressive and schizophrenic patients in comparison with healthy subjects

1998 ◽  
Vol 13 (6) ◽  
pp. 303-309 ◽  
Author(s):  
I Berlin ◽  
L Givry-Steiner ◽  
Y Lecrubier ◽  
AJ Puech
Keyword(s):  
Major Depression ◽  
Healthy Subjects ◽  
Sweet Taste ◽  
Taste Perception ◽  
Social Anhedonia ◽  
Perception Threshold ◽  
Sucrose Solutions ◽  
Scale Scores ◽  
Schizophrenic Patients ◽  
Depressive Patients

SummaryAnhedonia may be considered as a transnosological feature of depression and schizophrenia. The aim of the present study was to assess hedonic responses to sucrose solutions and sweet taste perception threshold in patients with major depression and in schizophrenic patients in comparison with healthy subjects (matched for age and gender with depressive patients), and to compare these responses to evaluations by the Physical and Social Anhedonia scale of Chapman and the Pleasure Scale of Fawcett, generally used to quantify anhedonia. Hedonic responses to sucrose solutions were similar in patients with major depression (n = 20), schizophrenia (n = 20), and healthy controls (n = 20). Sweet taste perception threshold was significantly higher in depressive patients than in controls. Hedonic response to sucrose was inversely correlated with physical Anhedonia Scores and sweet taste perception threshold with Pleasure Scale scores. Measures of hedonia/anhedonia were not related with the intensity of depression or anxiety as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale, respectively. In 11 depressed patients hospitalised for 17 to 33 days, neither hedonic ratings to sucrose solutions, sweet taste perception threshold, Physical, Social Anhedonia scores nor Pleasure Scale scores were modified in spite of substantial decrease in MADRS or Hamilton Anxiety scores. Hedonic responses to sucrose solutions and sweet taste perception threshold may be used as complementary evaluation to quantify anhedonia.

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