Variation in sequence and expression of the avian FTO, and association with glucose metabolism, body weight, fatness and body composition in chickens

Jia, Xiaoyun; Nie, Qinghua; Lamont, Susan J.; Zhang, Xiquan

doi:10.1038/ijo.2011.221

Cited by 26 publications

(29 citation statements)

References 46 publications

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“…Expression of FTO in the hypothalamic nuclei involved in energy balance regulation has been shown to respond to nutritional manipulations such as feeding and fasting [34]–[36]. Fasting has been shown to also increase FTO gene expression in the cerebrum, liver, breast muscle and subcutaneous fat.…”

Section: Discussionmentioning

confidence: 99%

Expression of miR-33 from an SREBF2 Intron Targets the FTO Gene in the Chicken

Shao

Wang

et al. 2014

PLoS ONE

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The sterol regulatory element binding transcription factor 2 (SREBF2) gene encodes a transcription factor that activates the expression of many genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids. Through bioinformatics, we found that intron 16 of the chicken SREBF2 gene might encode the chicken miR-33. Using quantitative RT-PCR, we detected the expression of miR-33 in a variety of chicken tissues including skeletal muscle, adipose tissue, and liver. Three hundred and seventy eight genes were predicted to be potential targets of miR-33 in chickens via miRNA target prediction programs “miRanda” and “TargetScan”. Among these targets, the gene FTO (fat mass and obesity associated) encodes a Fe(II)- and 2-oxoglutarate-dependent nucleic acid demethylase that regulates lipid metabolism, and the possibility that its expression is negatively regulated by miR-33 in the chicken liver was therefore further studied. Co-transfection and dual-luciferase reporter assays showed that the expression of luciferase reporter gene linked to the 3′-untranslated region (3′UTR) of the chicken FTO mRNA was down-regulated by overexpression of the chicken miR-33 in the C2C12 cells (P<0.05). Furthermore, this down-regulation was completely abolished when the predicted miR-33 target site in the FTO 3′UTR was mutated. In contrast, the expression of FTO mRNA in the primary chicken hepatocytes was up-regulated after transfection with the miR-33 inhibitor LNA-anti-miR-33. Using quantitative RT-PCR, we also found that the expression of miR-33 was increased in the chicken liver from day 0 to day 49 of age, whereas that of the FTO mRNA was decreased during the same age period. These data together suggest that miR-33 might play an important role in lipid metabolism in the chicken liver by negatively regulating the expression of the FTO gene.

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Section: Discussionmentioning

confidence: 99%

Expression of miR-33 from an SREBF2 Intron Targets the FTO Gene in the Chicken

Shao

Wang

et al. 2014

PLoS ONE

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“…Additionally, FTO was also reported to be involved in STAT3 or C/EBPβ-mediated inflammatory pathways. Overexpression of FTO remarkably increased STAT3 expression in the arcuate nucleus of the hypothalamus in rats [10] and in the chick embryonic fibroblast cells [38]. Also, FTO was found to act as a transcriptional coactivator to enhance the binding of C/EBPβ to the promoter of target genes [17].…”

Section: Discussionmentioning

confidence: 99%

LPS-induced inflammation in the chicken is associated with CCAAT/enhancer binding protein beta-mediated fat mass and obesity associated gene down-regulation in the liver but not hypothalamus

Zhang

Guo

et al. 2013

BMC Vet Res

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BackgroundThe fat mass and obesity associated gene (FTO) is widely investigated in humans regarding its important roles in obesity and type 2 diabetes. Studies in mammals demonstrate that FTO is also associated with inflammation markers. However, the association of FTO with inflammation in chickens remains unclear. In this study, male chickens on day 28 posthatching were injected intraperitoneally with lipopolysaccharide (LPS) or saline to investigate whether the FTO gene is involved in LPS-induced inflammation.ResultsWe detected significant down-regulation of FTO mRNA in the liver (P < 0.01), but not in the hypothalamus, 2 and 24 h after LPS challenge. Toll-like receptor (TLR) 2 (P < 0.01) and TLR4 (P < 0.01) followed the same pattern as FTO, being suppressed significantly in liver but not in hypothalamus. IL-1β was dramatically up-regulated (P < 0.01) in both liver and hypothalamus 2 h after LPS challenge, while activation of IL-6 was observed in the liver (P < 0.01), but not in hypothalamus. The 5′-flanking sequence of the chicken FTO gene contains nine predicted binding sites for CCAAT/enhancer binding protein beta (C/EBP beta) and one for signal transducer and activator of transcription 3 (STAT3). Significant elevation of C/EBP beta was detected in the liver (P < 0.01), but not in the hypothalamus, 2 h after LPS challenge. Lipopolysaccharide challenge increased the C/EBP beta binding to FTO promoter in the liver (P < 0.01 for fragment 1, P < 0.05 for fragment 2), although the protein content of C/EBP beta was not altered. Moreover, injection of LPS resulted in enhanced phosphorylation of liver STAT3, a downstream transcription factor in IL-6 signaling. Although phosphorylated STAT3 was not detected to directly bind to FTO promoter, it was found to interact with C/EBP beta.ConclusionOur results reveal that FTO expression in liver, but not in hypothalamus, is affected by the i.p. injection of LPS, which may be mediated through tissue-specific FTO transcriptional regulation by C/EBP beta and STAT3 interaction.

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“…Multiple comparisons were performed to calculate the least square means (LSM) by the Duncan’s Multiple Range test. Details are reported in our previous study34.…”

Section: Methodsmentioning

confidence: 99%

A short insertion mutation disrupts genesis of miR-16 and causes increased body weight in domesticated chicken

Jia

Lin

Nie

et al. 2016

Sci Rep

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Body weight is one of the most important quantitative traits with high heritability in chicken. We previously mapped a quantitative trait locus (QTL) for body weight by genome-wide association study (GWAS) in an F2 chicken resource population. To identify the causal mutations linked to this QTL, expression profiles were determined on livers of high-weight and low-weight chicken lines by microarray. Combining the expression pattern with SNP effects by GWAS, miR-16 was identified as the most likely potential candidate with a 3.8-fold decrease in high-weight lines. Re-sequencing revealed that a 54-bp insertion mutation in the upstream region of miR-15a-16 displayed high allele frequencies in high-weight commercial broiler line. This mutation resulted in lower miR-16 expression by introducing three novel splicing sites instead of the missing 5′ terminal splicing of mature miR-16. Elevating miR-16 significantly inhibited DF-1 chicken embryo cell proliferation, consistent with a role in suppression of cellular growth. The 54-bp insertion was significantly associated with increased body weight, bone size and muscle mass. Also, the insertion mutation tended towards fixation in commercial broilers (Fst > 0.4). Our findings revealed a novel causative mutation for body weight regulation that aids our basic understanding of growth regulation in birds.

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Variation in sequence and expression of the avian FTO, and association with glucose metabolism, body weight, fatness and body composition in chickens

Cited by 26 publications

References 46 publications

Expression of miR-33 from an SREBF2 Intron Targets the FTO Gene in the Chicken

Expression of miR-33 from an SREBF2 Intron Targets the FTO Gene in the Chicken

LPS-induced inflammation in the chicken is associated with CCAAT/enhancer binding protein beta-mediated fat mass and obesity associated gene down-regulation in the liver but not hypothalamus

A short insertion mutation disrupts genesis of miR-16 and causes increased body weight in domesticated chicken

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