Hypomorphism of Fto and Rpgrip1l causes obesity in mice

Stratigopoulos, George; Burnett, Lisa C.; Rausch, Richard; Gill, Richard; Penn, David Barth; Skowronski, Alicja A.; LeDuc, Charles A.; Lanzano, A; Zhang, Pumin; Storm, Daniel R.; Egli, Dieter; Leibel, Rudolph L.

doi:10.1172/jci85526

Cited by 88 publications

(108 citation statements)

References 55 publications

(83 reference statements)

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“…Thus, improper control of m 6 A levels could be a major source of human disease. However, this view was overturned by several studies that showed that obesity-associated FTO mutations do not affect the FTO protein; instead, such mutations affect the expression of neighboring genes (Claussnitzer et al 2015, Smemo et al 2014, Stratigopoulos et al 2016). The mutations are located primarily in intron 1 of FTO , and chromosome interaction analysis showed that this region is an enhancer that controls the expression of neighboring genes Irx3 and RPGRIP1L .…”

Section: Ftomentioning

confidence: 99%

Rethinking m⁶A Readers, Writers, and Erasers

Meyer

Jaffrey

2017

Annu. Rev. Cell Dev. Biol.

857

872

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In recent years, m6A has emerged as an abundant and dynamically regulated modification throughout the transcriptome. Recent technological advances have enabled the transcriptome-wide identification of m6A residues, which in turn has provided important insights into the biology and regulation of this pervasive regulatory mark. Also central to our current understanding of m6A are the discovery and characterization of m6A readers, writers, and erasers. Over the last few years, studies into the function of these proteins have led to important discoveries about the regulation and function of m6A. However, during this time our understanding of these proteins has also evolved considerably, sometimes leading to the reversal of early conceptions regarding the reading, writing and erasing of m6A. In this review, we summarize recent advances in m6A research, and we highlight how these new findings have reshaped our understanding of how m6A is regulated in the transcriptome.

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Section: Ftomentioning

confidence: 99%

Rethinking m⁶A Readers, Writers, and Erasers

Meyer

Jaffrey

2017

Annu. Rev. Cell Dev. Biol.

857

872

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“…More recent studies show that obesity-linked FTO mutations do not affect the FTO protein; instead, they affect the expression of neighboring genes [31][32][33]. More recent studies show that obesity-linked FTO mutations do not affect the FTO protein; instead, they affect the expression of neighboring genes [31][32][33].…”

Section: Reversible Rna Modification Hypothesis and Ftomentioning

confidence: 99%

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications

2018

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The fate of mRNA is regulated by epitranscriptomic nucleotide modifications, the most abundant of which is N -methyladenosine (m A). Although the pattern and distribution of m A in mRNA is mediated by specific methyltransferases, a recent hypothesis is that specific demethylases or 'erasers' allow m A to be dynamically reversed by signaling pathways. In this Review, we discuss the data in support and against this model. New insights into the function of fat mass and obesity-associated protein (FTO), the original enzyme thought to be an m A eraser, reveal that its physiologic target is not m A, but instead is N ,2'-O-dimethyladenosine (m A ). Another m A demethylase, ALKBH5, appears to have functions limited to sperm development in normal mice. Overall, the majority of the data suggest that m A is generally not reversible, although m A may be susceptible to demethylation in pathophysiological states such as cancer.

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“…Additional data are needed to discern the specific regions and pathways in which fMRI-assessed responses to food cues are most closely linked to food choice, macronutrient regulation, or caloric consumption. Finally, research into molecular mechanisms by which allelic variation conveys higher obesity risk is ongoing [93, 98], but recent rodent data show that impaired leptin signaling in neurons could link polymorphisms in FTO to hyperphagia and weight gain [*99, 98]. …”

Section: Limitations Of the Current Literature And Future Directionsmentioning

confidence: 99%

What Twin Studies Tell Us About Brain Responses to Food Cues

Schur

Carnell

2017

Curr Obes Rep

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Purpose of review Functional magnetic resonance imaging (fMRI) using visual food cues provides insight into brain regulation of appetite in humans. This review sought evidence for genetic determinants of these responses. Recent findings Echoing behavioral studies of food cue responsiveness, twin study approaches detect significant inherited influences on brain response to food cues. Both polygenic (whole genome) factors and polymorphisms in single genes appear to impact appetite regulation, particularly in brain regions related to satiety perception. Furthermore, genetic confounding might underlie findings linking obesity to stereotypical response patterns on fMRI, i.e., associations with obesity may actually reflect underlying inherited susceptibilities rather than acquired levels of adiposity. Summary Insights from twin studies show that genes powerfully influence brain regulation of appetite, emphasizing the role of inherited susceptibility factors in obesity risk. Future research to delineate mechanisms of inherited obesity risk could lead to novel or more targeted interventional approaches.

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Hypomorphism of Fto and Rpgrip1l causes obesity in mice

Cited by 88 publications

References 55 publications

Rethinking m⁶A Readers, Writers, and Erasers

Rethinking m⁶A Readers, Writers, and Erasers

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications

What Twin Studies Tell Us About Brain Responses to Food Cues

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Hypomorphism of Fto and Rpgrip1l causes obesity in mice

Cited by 88 publications

References 55 publications

Rethinking m6A Readers, Writers, and Erasers

Rethinking m6A Readers, Writers, and Erasers

FTO, m6Am, and the hypothesis of reversible epitranscriptomic mRNA modifications

What Twin Studies Tell Us About Brain Responses to Food Cues

Contact Info

Product

Resources

About

Rethinking m⁶A Readers, Writers, and Erasers

Rethinking m⁶A Readers, Writers, and Erasers

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications