Role of FTO in Adipocyte Development and Function: Recent Insights

Merkestein, Myrte; Sellayah, Dyan

doi:10.1155/2015/521381

Cited by 26 publications

(25 citation statements)

References 77 publications

(99 reference statements)

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“…We did not observe any effects on transcript stability or translational differences in Fto-regulated targets. Contrary to others, we did not find differential splicing of Runx1t1 in response to Fto knockdown (52,89), suggesting that demethylation of m6A RNA in adipocytes may not be Fto's critical function. We identified Cebpb and Cebpd as targets of Fto.…”

Section: Discussioncontrasting

confidence: 99%

FTO mediates cell-autonomous effects on adipogenesis and adipocyte lipid content by regulating gene expression via 6mA DNA modifications

Carli

LeDuc

Zhang

et al. 2018

Journal of Lipid Research

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SNPs in the first intron of α-ketoglutarate-dependent dioxygenase () convey effects on adiposity by mechanisms that remain unclear, but appear to include modulation of expression of itself, as well as other genes in expression is lower in fibroblasts and iPSC-derived neurons of individuals segregating for obesity risk alleles. We employed in vitro adipogenesis models to investigate the molecular mechanisms by which Fto affects adipocyte development and function. expression was upregulated during adipogenesis, and was required for the maintenance of and/ expression in murine and human adipocytes in vitro. knockdown decreased the number of 3T3-L1 cells that differentiated into adipocytes as well as the amount of lipid per mature adipocyte. This effect on adipocyte programming was conveyed, in part, by modulation of CCAAT enhancer binding protein (C/ebp)β-regulated transcription. We found that Fto also affected transcription by demethylating DNA N6-methyldeoxyadenosine in the promoter. Fto is permissive for adipogenesis and promotes maintenance of lipid content in mature adipocytes by enabling C/ebpβ-driven transcription and expression of These findings are consistent with the loss of fat mass in mice segregating for a dominant-negative allele.

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Section: Discussioncontrasting

confidence: 99%

FTO mediates cell-autonomous effects on adipogenesis and adipocyte lipid content by regulating gene expression via 6mA DNA modifications

Carli

LeDuc

Zhang

et al. 2018

Journal of Lipid Research

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show abstract

“…The FTO gene (MGI: 1347093), encoding the fat mass and obesity‐associated protein, was the first GWAS‐identified obesity and obesity‐related trait‐associated gene (ie, type 2 diabetes, hip circumference, bodyweight index, bodyweight) . Owing to the various studies of FTO association with obesity and obesity‐related phenotypes, it is now evident that FTO is highly expressed in adipose tissues, playing a crucial role in adipogenesis (cross‐talk with Irx3 ) and extremely involved in early development, and yet its function is still obscure beyond the adipose tissue . In relevance to liver weight phenotype, studies of FTO homozygous, null mice reported postnatal growth retardation accompanied by decreased bodyweight (lean and fat weight), suggesting the complex and major role of FTO in body development and composition, whether independently or by co‐regulatory mechanisms with the Irx B cluster and Rpgrip 1l gene .…”

Section: Resultsmentioning

confidence: 99%

Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice

Atamni

Botzman

Mott

et al. 2018

Anim Models and Exp Med

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Background Liver weight is a complex trait, controlled by polygenic factors and differs within populations. Dissecting the genetic architecture underlying these variations will facilitate the search for key role candidate genes involved directly in the hepatomegaly process and indirectly involved in related diseases etiology. Methods Liver weight of 506 mice generated from 39 different Collaborative Cross ( CC ) lines with both sexes at age 20 weeks old was determined using an electronic balance. Genomic DNA of the CC lines was genotyped with high‐density single nucleotide polymorphic markers. Results Statistical analysis revealed a significant ( P < 0.05) variation of liver weight between the CC lines, with broad sense heritability ( H 2 ) of 0.32 and genetic coefficient of variation ( CV G ) of 0.28. Subsequently, quantitative trait locus ( QTL ) mapping was performed, and results showed a significant QTL only for females on chromosome 8 at genomic interval 88.61‐93.38 Mb (4.77 Mb). Three suggestive QTL were mapped at chromosomes 4, 12 and 13. The four QTL were designated as LWL 1‐ LWL 4 referring to liver weight loci 1‐4 on chromosomes 8, 4, 12 and 13, respectively. Conclusion To our knowledge, this report presents, for the first time, the utilization of the CC for mapping QTL associated with baseline liver weight in mice. Our findings demonstrate that liver weight is a complex trait controlled by multiple genetic factors that differ significantly between sexes.

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“…The association between genetic variants within the fat mass and obesity-associated ( FTO ) gene and metabolic syndrome is widely reported [ 68 ]. FTO encodes an alpha-ketoglutarate-dependent dioxygenase, which plays a role in adipocyte development and function [ 69 ]. Three SNPs within the FTO gene were studied for GDM.…”

Section: Single-nucleotide Polymorphismsmentioning

confidence: 99%

Molecular Biomarkers for Gestational Diabetes Mellitus

Dias

Pheiffer

Abrahams

et al. 2018

IJMS

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Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included “gestational diabetes mellitus”, “blood”, “single-nucleotide polymorphism (SNP)”, “DNA methylation”, and “microRNAs”, including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.

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Role of FTO in Adipocyte Development and Function: Recent Insights

Cited by 26 publications

References 77 publications

FTO mediates cell-autonomous effects on adipogenesis and adipocyte lipid content by regulating gene expression via 6mA DNA modifications

FTO mediates cell-autonomous effects on adipogenesis and adipocyte lipid content by regulating gene expression via 6mA DNA modifications

Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice

Molecular Biomarkers for Gestational Diabetes Mellitus

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