scholarly journals Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Poonamjot Deol ◽  
Elena Kozlova ◽  
Matthew Valdez ◽  
Catherine Ho ◽  
Ei-Wen Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Soybean Oil ◽  
Messenger Rna ◽  
Control Diet ◽  
Coconut Oil ◽  
Metabolic Phenotype ◽  
Sequencing Analysis ◽  
Male Mice ◽  
Metabolic Inflammation ◽  
Obesity And Diabetes

Abstract Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.

scholarly journals High Levels of Prebiotic Resistant Starch in Diet Modulate Gene Expression and Metabolomic Profile in Pancreatic Cancer Xenograft Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 709 ◽  
Author(s):  
Concetta Panebianco ◽  
Annacandida Villani ◽  
Valerio Pazienza
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Resistant Starch ◽  
Control Diet ◽  
Metabolic Phenotype ◽  
Cancer Drug ◽  
Nutritional Interventions ◽  
Cancer Drug Resistance ◽  
Xenograft Mice ◽  
The Impact

Cancer initiation and protection mainly derives from a systemic metabolic environment regulated by dietary patterns. Less is known about the impact of nutritional interventions in people with a diagnosis of cancer. The aim of our study was to investigate the effect of a diet rich in resistant starch (RS) on cell pathways modulation and metabolomic phenotype in pancreatic cancer xenograft mice. RNA-Seq experiments on tumor tissue showed that 25 genes resulted in dysregulated pancreatic cancer in mice fed with an RS diet, as compared to those fed with control diet. Moreover, in these two different mice groups, six serum metabolites were deregulated as detected by LC–MS analysis. A bioinformatic prediction analysis showed the involvement of the differentially expressed genes on insulin receptor signaling, circadian rhythm signaling, and cancer drug resistance among the three top canonical pathways, whilst cell death and survival, gene expression, and neurological disease were among the three top disease and biological functions. These findings shed light on the genomic and metabolic phenotype, contributing to the knowledge of the mechanisms through which RS may act as a potential supportive approach for enhancing the efficacy of existing cancer treatments.

scholarly journals [6S]-5-Methyltetrahydrofolic Acid and Folic Acid Pregnancy Diets Differentially Program Metabolic Phenotype and Hypothalamic Gene Expression of Wistar Rat Dams Post-Birth

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 48
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Rebecca Simonian ◽  
Erland Arning ◽  
Paula Ashcraft ◽  
...  
Keyword(s):  
Gene Expression ◽  
Folic Acid ◽  
Food Intake ◽  
Rna Sequencing ◽  
Control Diet ◽  
Wistar Rat ◽  
Metabolic Phenotype ◽  
Maternal Metabolism ◽  
Plasma Hormones ◽  
Plasma Leptin

[6S]-5-methyltetrahydrofolic acid (MTHF) is a proposed replacement for folic acid (FA) in diets and prenatal supplements. This study compared the effects of these two forms on maternal metabolism and hypothalamic gene expression. Pregnant Wistar rats received an AIN-93G diet with recommended FA (1X, 2 mg/kg, control), 5X-FA or equimolar levels of MTHF. During lactation they received the control diet and then a high fat diet for 19-weeks post-weaning. Body weight, adiposity, food intake, energy expenditure, plasma hormones, folate, and 1-carbon metabolites were measured. RNA-sequencing of the hypothalamus was conducted at parturition. Weight-loss from weaning to 1-week post-weaning was less in dams fed either form of the 5X vs. 1X folate diets, but final weight-gain was higher in 5X-MTHF vs. 5X-FA dams. Both doses of the MTHF diets led to 8% higher food intake and associated with lower plasma leptin at parturition, but higher leptin at 19-weeks and insulin resistance at 1-week post-weaning. RNA-sequencing revealed 279 differentially expressed genes in the hypothalamus in 5X-MTHF vs. 5X-FA dams. These findings indicate that MTHF and FA differ in their programing effects on maternal phenotype, and a potential adverse role of either form when given at the higher doses.

scholarly journals Triplet Male Lambs Are More Susceptible than Twins to Dietary Soybean Oil–Induced Fatty Liver

2019 ◽  
Vol 149 (6) ◽  
pp. 989-995
Author(s):  
Bo Wang ◽  
Yanghua Qu ◽  
Yiping Wang ◽  
Yong Ma ◽  
Chenchen Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Liver ◽  
Soybean Oil ◽  
Differentially Expressed Genes ◽  
Litter Size ◽  
Hepatic Lipase ◽  
Control Diet ◽  
Liver Steatosis ◽  
Differentially Expressed ◽  
Nonesterified Fatty Acid

ABSTRACT Background Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. Objectives This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil–supplemented diet. Methods Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil–supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). Results SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). Conclusions TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.

2031-P: Adipose-Specific Lack of Hexose-6-Phosphate Dehydrogenase Causes Inactivation of Adipose Glucocorticoids and Improves Metabolic Phenotype in Male Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2031-P
Author(s):  
JIAN WANG ◽  
XINXIANG WANG ◽  
KABIRULLAH LUTFY ◽  
THEODORE FRIEDMAN ◽  
MEISHENG JIANG ◽  
...  
Keyword(s):  
Metabolic Phenotype ◽  
Male Mice

PENGARUH PENGGUNAAN VIRGIN COCONUT OIL (VCO) DALAM RANSUM TERHADAP PERFORMANS TERNAK BABI FASE STARTER

ZOOTEC ◽  
2015 ◽  
Vol 35 (2) ◽  
pp. 86
Author(s):  
Alfred Tamawiwy ◽  
M. Najoan ◽  
J S Mandey ◽  
F. N Sompie
Keyword(s):  
Water Consumption ◽  
Feed Intake ◽  
Control Diet ◽  
Coconut Oil ◽  
Growing Pigs ◽  
Virgin Coconut Oil ◽  
Daily Water ◽  
Pig Performance ◽  
Daily Gain ◽  
Daily Water Consumption

ABSTRACT   EFFECT OF UTILIZATION OF VIRGIN COCONUT OIL (VCO) IN THE DIET ON PIG PERFORMANCE. Utilization of fats and oils in pig diets is of great importance due to their high energy value. VCO is obtained by cold press processing of the kernel from the coconut fruit. Utilization of virgin coconut oil (VCO) in the diets on pig performance.  The present study was designed to elaborate the effect of utilization of VCO in the diets on energy and protein digestibility of growing pigs. The experiment was conducted using 20 castrated male pigs aged 1.5 - 2.0 months weighing 12,0±2,0 kg. The data were analyzed according to the linear model procedure for ANOVA appropriate for Randomized Block Design with 5 treatments and 4 replications. Treatments were formulated as follow: R0 = 100% control diet + 0% VCO; R1 = 99.5% control diet + 1.0% VCO; R2 = 98.0% control diet + 2.0% VCO; R3 = 97.0% control diet + 3.0% VCO; and R4 = 96.0% control diet + 4.0% VCO. Parameters measured were: daily feed intake, daily gain, daily water consumption. The results showed that the utilization of VCO up to 4% in the diets had no significant effect (P > 0.05) on daily feed intake, daily gain, daily water consumption of pigs. It can be concluded that the addition of VCO up to 4.0% in the diets has no significant meaning on pig performance.   Key words: Virgin coconut oil (VCO), Performance, Growing pigs  

A New Approach for Predicting the Value of Gene Expression: Two-way Collaborative Filtering

2019 ◽  
Vol 14 (6) ◽  
pp. 480-490 ◽  
Author(s):  
Tuncay Bayrak ◽  
Hasan Oğul
Keyword(s):  
Gene Expression ◽  
Regression Model ◽  
Collaborative Filtering ◽  
High Throughput Sequencing ◽  
Mean Squared Error ◽  
Experimental Studies ◽  
Kernel Functions ◽  
Feature Representation ◽  
Sequencing Analysis ◽  
Computational Systems Biology

Background: Predicting the value of gene expression in a given condition is a challenging topic in computational systems biology. Only a limited number of studies in this area have provided solutions to predict the expression in a particular pattern, whether or not it can be done effectively. However, the value of expression for the measurement is usually needed for further meta-data analysis. Methods: Because the problem is considered as a regression task where a feature representation of the gene under consideration is fed into a trained model to predict a continuous variable that refers to its exact expression level, we introduced a novel feature representation scheme to support work on such a task based on two-way collaborative filtering. At this point, our main argument is that the expressions of other genes in the current condition are as important as the expression of the current gene in other conditions. For regression analysis, linear regression and a recently popularized method, called Relevance Vector Machine (RVM), are used. Pearson and Spearman correlation coefficients and Root Mean Squared Error are used for evaluation. The effects of regression model type, RVM kernel functions, and parameters have been analysed in our study in a gene expression profiling data comprising a set of prostate cancer samples. Results: According to the findings of this study, in addition to promising results from the experimental studies, integrating data from another disease type, such as colon cancer in our case, can significantly improve the prediction performance of the regression model. Conclusion: The results also showed that the performed new feature representation approach and RVM regression model are promising for many machine learning problems in microarray and high throughput sequencing analysis.

scholarly journals Activation of the S100A7/RAGE Pathway by IGF-1 Contributes to Angiogenesis in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 621
Author(s):  
Maria Grazia Muoio ◽  
Marianna Talia ◽  
Rosamaria Lappano ◽  
Andrew H. Sims ◽  
Veronica Vella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Bioinformatic Analysis ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Diabetic Patients ◽  
Obesity And Diabetes ◽  
Er Positive

Background: Breast cancer (BC) mortality is increased among obese and diabetic patients. Both obesity and diabetes are associated with dysregulation of both the IGF-1R and the RAGE (Receptor for Advanced Glycation End Products) pathways, which contribute to complications of these disorders. The alarmin S100A7, signaling through the receptor RAGE, prompts angiogenesis, inflammation, and BC progression. Methods: We performed bioinformatic analysis of BC gene expression datasets from published studies. We then used Estrogen Receptor (ER)-positive BC cells, CRISPR-mediated IGF-1R KO BC cells, and isogenic S100A7-transduced BC cells to investigate the role of IGF-1/IGF-1R in the regulation of S100A7 expression and tumor angiogenesis. To this aim, we also used gene silencing and pharmacological inhibitors, and we performed gene expression and promoter studies, western blotting analysis, ChIP and ELISA assays, endothelial cell proliferation and tube formation assay. Results: S100A7 expression correlates with worse prognostic outcomes in human BCs. In BC cells, the IGF-1/IGF-1R signaling engages STAT3 activation and its recruitment to the S100A7 promoter toward S100A7 increase. In human vascular endothelial cells, S100A7 activates RAGE signaling and prompts angiogenic effects. Conclusions: In ER-positive BCs the IGF-1 dependent activation of the S100A7/RAGE signaling in adjacent endothelial cells may serve as a previously unidentified angiocrine effector. Targeting S100A7 may pave the way for a better control of BC, particularly in conditions of unopposed activation of the IGF-1/IGF-1R axis.

scholarly journals A Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 95
Author(s):  
Imran Ramzan ◽  
Moira Taylor ◽  
Beth Phillips ◽  
Daniel Wilkinson ◽  
Kenneth Smith ◽  
...  
Keyword(s):  
Amino Acids ◽  
Pilot Study ◽  
Dietary Intervention ◽  
Control Diet ◽  
Branched Chain Amino Acids ◽  
Model Assessment ◽  
Dietary Intakes ◽  
Restricted Diet ◽  
Obesity And Diabetes ◽  
Branched Chain

Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.

scholarly journals The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihao Fang ◽  
Yiqiu Hu ◽  
Jinhui Hu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Regulatory Proteins ◽  
Biological Processes ◽  
The Past ◽  
Common Cancer ◽  
Potential Applications ◽  
Regulated Gene Expression

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

scholarly journals Mammalian GW220/TNGW1 is essential for the formation of GW/P bodies containing miRISC

2012 ◽  
Vol 198 (4) ◽  
pp. 529-544 ◽  
Author(s):  
Virginia Castilla-Llorente ◽  
Lee Spraggon ◽  
Miwako Okamura ◽  
Saif Naseeruddin ◽  
Matthew Adamow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Cellular Localization ◽  
Translational Repression ◽  
P Bodies ◽  
Target Mrna ◽  
Core Components ◽  
Mirna Pathway

The microRNA (miRNA)-induced silencing complex (miRISC) controls gene expression by a posttranscriptional mechanism involving translational repression and/or promoting messenger RNA (mRNA) deadenylation and degradation. The GW182/TNRC6 (GW) family proteins are core components of the miRISC and are essential for miRNA function. We show that mammalian GW proteins have distinctive functions in the miRNA pathway, with GW220/TNGW1 being essential for the formation of GW/P bodies containing the miRISC. miRISC aggregation and formation of GW/P bodies sequestered and stabilized translationally repressed target mRNA. Depletion of GW220 led to the loss of GW/P bodies and destabilization of miRNA-targeted mRNA. These findings support a model in which the cellular localization of the miRISC regulates the fate of the target mRNA.

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