IRX3

The enzyme nicotidamide-N-methyltransferase (NNMT) regulates adipose tissue energy expenditure through increasing nicotinamide adenosine dinucleotide (NAD+ ) content. NNMT methylates nicotinamide to N1 -methylnicotidamide (MNA-1) using S-adenosyl methionine. The rs694539 NNMT polymorphism is associated with non-alcoholic steatohepatitis, and rs1941404 is associated with hyperlipidemia. The rs1421085 FTO is related to poor eating behaviors, and rs3751723 IRX3 is associated with obesity. To investigate the association of rs694539 and rs1941404 NNMT, rs140285 FTO and rs3751723 IRX3 polymorphisms with MNA-1 concentrations, resting energy expenditure (REE) and BMI, we included clinically healthy Mexican subjects 30 to 50 years old, 100 subjects (35 men/65 women) with BMI > 30 kg/m2 and 100 subjects (32 men/68 women) with BMI < 25 kg/m2 ...

Bama minipigs are a local pig breed that is unique to China and has a high development and utilization value. However, its high fat content, low feed utilization rate, and slow growth rate have limited its popularity and utilization. Compared with the long breeding cycle and high cost of traditional genetic breeding of pigs, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) endonuclease 9 system (CRISPR/Cas9)-mediated gene editing can cost-effectively implement targeted mutations in animal genomes, thereby providing a powerful tool for rapid improvement of the economic traits of Bama minipigs...

Members of the Iroquois B ( IrxB ) homeodomain cluster genes, specifically Irx3 and Irx5 , are critical for heart, limb, and bone development. Recently, we reported their importance for oocyte and follicle survival within the developing ovary. Irx3 and Irx5 expression begins after sex determination in the ovary but remains absent in the fetal testis. Mutually antagonistic molecular signals ensure ovary vs testis differentiation with canonical Wnt/β-catenin signals paramount for promoting the ovary pathway...

Genome-wide association studies (GWASs) have identified SNPs of the fat mass and obesity (FTO) gene as the most important risk alleles for obesity. However, how the presence of risk alleles affect phenotype is still a matter of intense investigation. In 2014, a study revealed that long-range enhancers from the intronic regions of the FTO gene regulate iroquois-class homeobox protein (IRX)3 expression. IRX3 is expressed in hypothalamic pro-opiomelanocortin (POMC) neurons and changes in its expression levels affect body adiposity by modifying food intake and energy expenditure...

BACKGROUND: Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function. Although altered neural development and function have been well described in people with DS, few studies have investigated the etiology underlying the observed motor phenotypes. Here, we examine the development, patterning, and organization of the spinal cord throughout life in the Ts65Dn mouse, a model that recapitulates many of the motor changes observed in people with DS...

This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients' intake were assessed at baseline and after 18 weeks of the intervention...

BACKGROUND: Inhibition of Irx3 and Irx5 has been shown to reduce body weight and white adipose tissue (WAT) mass through cell-autonomous and sympathetic-induced increases in adipocyte beiging and thermogenesis in mice and humans. However, the underlying mechanisms of the Irx control over beiging are still largely unknown, as illustrated by recent reports showing divergent effects of Irx3 on adipocyte metabolism and function. Here, we investigated the role of Irx3 in controlling beige preadipocyte function and differentiation...

Neurogenesis is the process by which undifferentiated progenitor cells develop into mature and functional neurons. Defects in neurogenesis are associated with neurodevelopmental and neuropsychiatric disorders; therefore, elucidating the molecular mechanisms underlying neurogenesis can advance our understanding of the pathophysiology of these disorders and facilitate the discovery of novel therapeutic targets. In this study, we performed a comparative transcriptomic analysis to identify common targets of the proneural transcription factors Neurog1/2 and Ascl1 during neurogenesis of human and mouse stem cells...

Introduction: Recent studies reported that FTO exert its effects on body weight through change the expression IRX3. The aim of this study was investigation of the possible mechanisms of the effects of IRX3 gene on obesity. Material and methods: The present review was carried out using keywords such as polymorphism and/or obesity and/or BMI and/or IRX3 gene and/or Iroquois homeobox protein 3. Databases including PubMed, Science Direct, web of sciences, Scopus, and Cochran databases were used to collect all related articles published from 2000 to 2019...

As a health-care food and traditional Chinese medicine, E'jiao, from the skin of Equus animus L, has been used to nourish blood in China for more than 2000 years. In modern medicine, there are also evidences indicate it has a beneficial effect on chemotherapy-caused blood deficiency. However, its mechanism of action for blood invigoration remains unclear. In the present study, we investigated the hematopoietic effect of E'jiao in 5-Fluorouracil-treated mice. In addition to the counting of bone marrow nucleated cells (BMNCs), flow cytometry was used to detect the population of hematopoietic stem cells (HSCs), and colony-forming unit (CFU) was used to assay the differentiation ability of hematopoietic progenitor cells (HPCs)...

Tibetan pigs from the Tibetan Plateau are characterized with a significant phenotypic difference relative to lowland pigs. In this study, a significant difference of the fatness and fatty acid composition traits was observed between the Tibetan and Yorkshire pigs. To uncover the involved mechanism, the expression profile of long noncoding RNAs (lncRNAs) and genes was compared between them. After serial filtered steps, 1,964 lncRNAs were obtained through our computational pipeline. In total, 63 and 715 lncRNAs and genes were identified to be differentially expressed...

BACKGROUND: Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of FTO genotype in this interaction. METHODS: This study was a field trial of 62 adolescents from boys' high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools...

In most of mammalian embryos, gonadal sex differentiation occurs inside the maternal uterus before birth. In several fetal ovarian grafting experiments using male host mice, an experimental switch from the maternal intrauterine to male-host environment gradually induces partial masculinization of the grafted ovaries even under the wild-type genotype. However, either host-derived factors causing or molecular basis underlying this masculinization of the fetal ovaries are not clear. Here, we demonstrate that ectopic appearance of SOX9-positive Sertoli cell-like cells in grafted ovaries was mediated by the testosterone derived from the male host...

OBJECTIVE: We investigated the association of IRX3 SNP rs3751723 with anthropometric characteristics related to adiposity and potential relationships with FTO SNP rs9939609 in a population of Brazilian children and adolescents. METHODS: A total of 871 children and adolescents between 7 and 17 years of age were recruited. Adiposity measurements and biochemical parameters were assessed. The variants were genotyped by real-time PCR. Analysis of multiple linear regression, multiple logistic regression, and generalised multifactor dimensionality reduction (GMDR) adjusted for sex, age and ethnicity were applied to test the polymorphisms association with obesity-related phenotypes and the interaction between them...

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OBJECTIVE: A causal obesity risk variant in the FTO locus was recently shown to inhibit adipocyte thermogenesis via increased adipose expression of the homeobox transcription factors IRX3 and IRX5. However, causal effects of IRX5 on fat storage remain to be shown in vivo, and discovery of downstream mediators may open new therapeutic avenues. METHODS: 17 WT and 13 Irx5 knockout (KO) mice were fed low-fat control (Ctr) or high-fat (HF) diet for 10 weeks. Body weight, energy intake and fat mass were measured...

BACKGROUND: The Iroquois homeobox 3 (Irx3) gene has been identified as a functional long-range target of obesity-associated variants within the fat mass and obesity-associated protein (FTO) gene. It is highly expressed in the hypothalamus, and both whole-body knockout and hypothalamic restricted abrogation of its expression results in a lean phenotype, which is mostly explained by the resulting increased energy expenditure in the brown adipose tissue. Because of its potential implication in the pathogenesis of obesity, we evaluated the hypothalamic cell distribution of Irx3 and the outcomes of inhibiting its expression in a rodent model of diet-induced obesity...

Gestational diabetes mellitus (GDM), which has an increasing global prevalence, contributes to the susceptibility to metabolic dysregulation and obesity in the offspring via epigenetic modifications. However, the underlying mechanism remains largely obscure. The current study established a GDM mice model to investigate the alternations in the metabolic phenotypes and genomic DNA methylation in the pancreas of the offspring. We found that in the GDM offspring, intrauterine hyperglycemia induced dyslipidemia, insulin resistance, and glucose intolerance...

Obesity is one of the largest global health problems associated with increased morbidity and mortality mediated by its association with several other metabolic disorders. The interaction between the genes and environment plays an important role in the manifestation of obesity. Despite a high heritability (40-70%) of obesity, the search for genetic variants associated with obesity susceptibility has been a challenging task. To date, limited studies have been conducted in India, restricted to the validation of few genetic variants identified by genomewide association studies...

BACKGROUND: The molecular mechanism of Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) remains elusive. A collection of molecular regulators including transcription factor and noncoding RNA (ncRNAs) may affect the carcinogenesis of EBVaGC by regulating the expression and function of key genes. In this study, integration of multi-level expression data and bioinformatics approach was used to identify key elements and their interactions involved in mechanism of EBVaGC and their network regulation...