Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic, and organismal phenotypes in vivo.

doi:10.1126/sciadv.abg0108

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Article

Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic, and organismal phenotypes in vivo.

Science advances - 1 Jul 2021

Laber Samantha, Forcisi Sara, Bentley Liz, Petzold Julia, Moritz Franco, Smirnov Kirill S, Al Sadat Loubna, Williamson Iain, Strobel Sophie, Agnew Thomas, Sengupta Shahana, Nicol Tom, Grallert Harald, Heier Margit, Honecker Julius, Mianne Joffrey, Teboul Lydia, Dumbell Rebecca, Long Helen, Simon Michelle, Lindgren Cecilia, Bickmore Wendy A, Hauner Hans, Schmitt-Kopplin Philippe, Claussnitzer Melina, Cox Roger D

Abstract excerpt

Variants in FTO have the strongest association with obesity; however, it is still unclear how those noncoding variants mechanistically affect whole-body physiology. We engineered a deletion of the rs1421085 conserved cis-regulatory module (CRM) in mice and confirmed in vivo that the CRM modulates Irx3 and Irx5 gene expression and mitochondrial function in adipocytes. The CRM affects molecular and cellular...

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PMID: 34290091
DOI: 10.1126/sciadv.abg0108
PMCID: PMC8294759

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